2022年10月, 日本アイソトープ協会, 放射線安全取扱部会表彰 功労賞　　　　　　　　　　　　　　　
久下裕司

2002年, 第40回 日本核医学会賞　　　　　　　　　　　　　　　
久下裕司, 日本国

Attenuated polyethylene glycol immunogenicity and overcoming accelerated blood clearance of a fully PEGylated dendrimer
Chie Kojima, Junjie Yao, Kohei Nakajima, Motofumi Suzuki, Ayako Tsujimoto, Yuji Kuge, Mikako Ogawa, Akikazu Matsumoto
International Journal of Pharmaceutics, 659, 124193, 124193, Elsevier BV, 2024年06月, ［査読有り］
研究論文（学術雑誌）

Feasibility study of multimodal imaging for redox status and glucose metabolism in tumor.
Kazuhiro Kato, Hironobu Yasui, Hideo Sato-Akaba, Miho C Emoto, Hirotada G Fujii, Maciej M Kmiec, Periannan Kuppusamy, Yuki Mizuno, Yuji Kuge, Masaki Nagane, Tadashi Yamashita, Osamu Inanami
Free radical biology & medicine, 2024年04月02日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Understanding the tumor redox status is important for efficient cancer treatment. Here, we noninvasively detected changes in the redox environment of tumors before and after cancer treatment in the same individuals using a novel compact and portable electron paramagnetic resonance imaging (EPRI) device and compared the results with glycolytic information obtained through autoradiography using 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG). Human colon cancer HCT116 xenografts were used in the mice. We used 3-carbamoyl-PROXYL (3CP) as a paramagnetic and redox status probe for the EPRI of tumors. The first EPRI was followed by the intraperitoneal administration of buthionine sulfoximine (BSO), an inhibitor of glutathione synthesis, or X-ray irradiation of the tumor. A second EPRI was performed on the following day. Autoradiography was performed after the second EPRI. After imaging, the tumor sections were evaluated by histological analysis and the amount of reducing substances in the tumor was measured. BSO treatment and X-ray irradiation significantly decreased the rate of 3CP reduction in tumors. Redox maps of tumors obtained from EPRI can be compared with tissue sections of approximately the same cross section. BSO treatment reduced glutathione levels in tumors, whereas X-ray irradiation did not alter the levels of any of the reducing substances. Comparison of the redox map with the autoradiography of [18F]FDG revealed that regions with high reducing power in the tumor were active in glucose metabolism; however, this correlation disappeared after X-ray irradiation. These results suggest that the novel compact and portable EPRI device is suitable for multimodal imaging, which can be used to study tumor redox status and therapeutic efficacy in cancer, and for combined analysis with other imaging modalities.

Application of copper (I) selective ligands for PET imaging of reactive oxygen species through metabolic trapping
Tetsuro Tada, Yuki Mizuno, Yuki Shibata, Hironobu Yasui, Yuji Kuge
Nuclear Medicine and Biology, 108914, 108914, Elsevier BV, 2024年04月, ［査読有り］
研究論文（学術雑誌）

Intravenous Administration of Mesenchymal Stem Cell-Derived Exosome Alleviates Spinal Cord Injury by Regulating Neutrophil Extracellular Trap Formation through Exosomal miR-125a-3p.
Yutaka Morishima, Masahito Kawabori, Kazuyoshi Yamazaki, Soichiro Takamiya, Sho Yamaguchi, Yo Nakahara, Hajime Senjo, Daigo Hashimoto, Sakiko Masuda, Yoichiro Fujioka, Yusuke Ohba, Yuki Mizuno, Yuji Kuge, Miki Fujimura
International journal of molecular sciences, 25, 4, 2024年02月18日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Spinal cord injury (SCI) leads to devastating sequelae, demanding effective treatments. Recent advancements have unveiled the role of neutrophil extracellular traps (NETs) produced by infiltrated neutrophils in exacerbating secondary inflammation after SCI, making it a potential target for treatment intervention. Previous research has established that intravenous administration of stem cell-derived exosomes can mitigate injuries. While stem cell-derived exosomes have demonstrated the ability to modulate microglial reactions and enhance blood-brain barrier integrity, their impact on neutrophil deactivation, especially in the context of NETs, remains poorly understood. This study aims to investigate the effects of intravenous administration of MSC-derived exosomes, with a specific focus on NET formation, and to elucidate the associated molecular mechanisms. Exosomes were isolated from the cell supernatants of amnion-derived mesenchymal stem cells using the ultracentrifugation method. Spinal cord injuries were induced in Sprague-Dawley rats (9 weeks old) using a clip injury model, and 100 μg of exosomes in 1 mL of PBS or PBS alone were intravenously administered 24 h post-injury. Motor function was assessed serially for up to 28 days following the injury. On Day 3 and Day 28, spinal cord specimens were analyzed to evaluate the extent of injury and the formation of NETs. Flow cytometry was employed to examine the formation of circulating neutrophil NETs. Exogenous miRNA was electroporated into neutrophil to evaluate the effect of inflammatory NET formation. Finally, the biodistribution of exosomes was assessed using 64Cu-labeled exosomes in animal positron emission tomography (PET). Rats treated with exosomes exhibited a substantial improvement in motor function recovery and a reduction in injury size. Notably, there was a significant decrease in neutrophil infiltration and NET formation within the spinal cord, as well as a reduction in neutrophils forming NETs in the circulation. In vitro investigations indicated that exosomes accumulated in the vicinity of the nuclei of activated neutrophils, and neutrophils electroporated with the miR-125a-3p mimic exhibited a significantly diminished NET formation, while miR-125a-3p inhibitor reversed the effect. PET studies revealed that, although the majority of the transplanted exosomes were sequestered in the liver and spleen, a notably high quantity of exosomes was detected in the damaged spinal cord when compared to normal rats. MSC-derived exosomes play a pivotal role in alleviating spinal cord injury, in part through the deactivation of NET formation via miR-125a-3p.

In vivo imaging of acute physiological responses after treatment of cancer with near-infrared photoimmunotherapy
Kohei Nakajima, Akiyo Sugikawa, Hironobu Yasui, Kei Higashikawa, Chie Suzuki, Takahiro Natsume, Motofumi Suzuki, Hideo Takakura, Mayu Tomita, Sachi Takahashi, Kenji Hirata, Yasuhiro Magata, Yuji Kuge, Mikako Ogawa
Molecular Imaging and Biology, Springer Science and Business Media LLC, 2023年05月16日, ［査読有り］
研究論文（学術雑誌）

PD1 blockade alters cell-cycle distribution and affects 3'-deoxy-3'-[18F]fluorothymidine uptake in a mouse CT26 tumor model.
Motofumi Suzuki, Takuma Matsuda, Kohei Nakajima, Yuta Yokouchi, Yuji Kuge, Mikako Ogawa
Annals of nuclear medicine, 2022年08月15日, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）, OBJECTIVE: We previously reported that alterations of the tumor microenvironment (TME) by programmed death receptor-1 (PD1) blockade affected tumor glucose metabolism and tumor 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) uptake. In cancer cells, high glycolysis allows cells to sustain rapid proliferation since glycolysis is closely related to the proliferation of cancer cells. Therefore, imaging of cellular proliferation may provide more detail of TME alterations. In this study, we investigated how TME alterations by PD1 blockade affects the uptake of 3'-deoxy-3'-[18F]fluorothymidine ([18F]FLT), which is a 18F-radiolabeled thymidine derivative and is taken up by proliferating cells. METHODS: Mice inoculated with murine colon carcinoma CT26 cells were intraperitoneally administered an anti-PD1 antibody on Day 0, when the tumor volume exceeded 50 mm3, and Day 5. [18F]FLT-PET imaging was performed pre-treatment (Day 0) and post treatment (Day 7). Tumor infiltrating lymphocytes (TILs) were identified by flow cytometry. [18F]FLT accumulation and localization in tumor tissue was evaluated by autoradiography and immunohistochemistry. The cell-cycle distribution of tumors and CT26 cells exposed to cytokines (interleukin-2, interferon [INF]-γ, and tumor necrosis factor [TNF]-α) was analyzed by flow cytometry. RESULTS: PD1 blockade increased CD8+ and CD4+ T cells in tumor tissue and significantly suppressed tumor proliferation; however, tumor [18F]FLT uptake remained unchanged. Autoradiography and immunohistochemistry showed that [18F]FLT was mainly taken up by cancer cells, but not TILs. Flow cytometric analysis demonstrated that the population of cells in G2/M phase increased after PD1 blockade. Moreover, INF-γ and TNF-α significantly increased cells in G2/M phase in vitro. CONCLUSION: PD1 blockade-induced alteration of the TME increased CT26 tumor cells in the G2/M phase, which have high thymidine kinase 1 activity. Therefore, [18F]FLT is taken up by tumor cells even if tumor proliferation is suppressed. This observation may be useful for evaluating the response to immunotherapy.

Intracerebral Transplantation of Mesenchymal Stromal Cell Compounded with Recombinant Peptide Scaffold against Chronic Intracerebral Hemorrhage Model
Soichiro Takamiya, Masahito Kawabori, Tsukasa Kitahashi, Kentaro Nakamura, Yuki Mizuno, Hironobu Yasui, Yuji Kuge, Aki Tanimori, Yasuyuki Takamatsu, Kohei Yuyama, Hideo Shichinohe, Miki Fujimura
Stem Cells International, 2022, 1, 10, Hindawi Limited, 2022年07月31日, ［査読有り］
研究論文（学術雑誌）, Background. Due to the lack of effective therapies, stem cell transplantation is an anticipated treatment for chronic intracerebral hemorrhage (ICH), and higher cell survival and engraftment are considered to be the key for recovery. Mesenchymal stromal cells (MSCs) compounded with recombinant human collagen type I scaffolds (CellSaics) have a higher potential for cell survival and engraftment compared with solo-MSCs, and we investigated the validity of intracerebral transplantation of CellSaic in a chronic ICH model. Methods. Rat CellSaics (rCellSaics) were produced by rat bone marrow-derived MSC (rBMSCs). The secretion potential of neurotrophic factors and the cell proliferation rate were compared under oxygen-glucose deprivation (OGD) conditions. rCellSaics, rBMSCs, or saline were transplanted into the hollow cavity of a rat chronic ICH model. Functional and histological analyses were evaluated, and single-photon emission computed tomography for benzodiazepine receptors was performed to monitor sequential changes in neuronal integrity. Furthermore, human CellSaics (hCellSaics) were transplanted into a chronic ICH model in immunodeficient rats. Antibodies neutralizing brain-derived neurotrophic factor (BDNF) were used to elucidate its mode of action. Results. rCellSaics demonstrated a higher secretion potential of trophic factors and showed better cell proliferation in the OGD condition. Animals receiving rCellSaics displayed better neurological recovery, higher intracerebral BDNF, and better cell engraftment; they also showed a tendency for less brain atrophy and higher benzodiazepine receptor preservation. hCellSaics also promoted significant functional recovery, which was reversed by BDNF neutralization. Conclusion. Intracerebral transplantation of CellSaics enabled neurological recovery in a chronic ICH model and may be a good option for clinical application.

Reduction of tumor hypoxia by anti-PD-1 therapy assessed using pimonidazole and [18F]FMISO
Kohei Nakajima, Mitsunori Homma, Motofumi Suzuki, Yuta Yokouchi, Takuma Matsuda, Hideo Takakura, Kenji Hirata, Yuji Kuge, Mikako Ogawa
Nuclear Medicine and Biology, 108-109, 85, 92, Elsevier BV, 2022年05月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, INTRODUCTION: Hypoxia is common in solid tumors and creates an immunosuppressive environment that leads to resistance to immunotherapy, such as an anti-programmed death receptor-1 (PD-1) therapy. It has been suggested that anti-PD-1 therapy may reduce tumor hypoxia by remodeling the tumor vasculature; however, it is unclear how anti-PD-1 therapy reduces hypoxia over time. Therefore, we investigated the relationship between hypoxia and immune activation by anti-PD-1 therapy in murine cancer models. METHODS: Anti-PD-1 antibody was injected to CT26- and MC38-tumor-bearing mice on days 0 and 5. Tumor hypoxia was non-invasively evaluated using positron emission tomography (PET) with [18F]fluoromisonidazole ([18F]FMISO) on days 3 and 7. Histological analysis was conducted to investigate the infiltration of immune cells in [18F]FMISO-accumulated hypoxic area. In addition, the immune cell population in tumors and the percentages of cancer and immune cells under hypoxic conditions were analyzed at single-cell level using flow cytometry. RESULTS: Flow cytometric analysis of CT26 tumors on day 3 showed that anti-PD-1 therapy reduced hypoxia without inhibition of tumor growth. In addition, the infiltration of CD8+ T cells was increased in treated tumors. In contrast to CT26 tumors, the percentage of hypoxic cells in MC38 tumors did not change on days 3 and 7, and there was minimal immune activation induced by anti-PD-1 antibody. Changes in hypoxia in CT26 tumors were not detected by [18F]FMISO-PET, but autoradiogram showed that [18F]FMISO accumulated in immunosuppressed areas, where the infiltration of immune cells was relatively low. CONCLUSION: Reduction of hypoxia was induced in CT26 tumor, in which adequate immune response to anti-PD-1 therapy was exhibited, at an early time point before suppression of tumor growth. Our findings suggest that anti-PD-1 therapy can create a tumor microenvironment that facilitates immune activation by reducing hypoxia.

68Ge/68Ga ジェネレータの長期間にわたる放射線管理上の安全性評価
富田 翔, 東川 桂, 水野雄貴, 多田哲朗, 田沢周作, 久下裕司
RADIOISOTOPES, 71, 1, 1, 8, Japan Radioisotope Association, 2022年03月15日, ［査読有り］
研究論文（学術雑誌）

Eribulin improves tumor oxygenation demonstrated by 18F-DiFA hypoxia imaging, leading to radio-sensitization in human cancer xenograft models
Tomoki Bo, Hironobu Yasui, Tohru Shiga, Yuki Shibata, Masaki Fujimoto, Motofumi Suzuki, Kei Higashikawa, Naoki Miyamoto, Osamu Inanami, Yuji Kuge
European Journal of Nuclear Medicine and Molecular Imaging, 49, 3, 821, 833, Springer Science and Business Media LLC, 2022年02月, ［査読有り］
研究論文（学術雑誌）

Influence of Linker Molecules in Hexavalent RGD Peptides on Their Multivalent Interactions with Integrin αvβ3
Yuki Mizuno, Kohta Kimura, Satoru Onoe, Miho Shukuri, Yuji Kuge, Hiromichi Akizawa
Journal of Medicinal Chemistry, 64, 21, 16008, 16019, American Chemical Society (ACS), 2021年11月03日, ［査読有り］
研究論文（学術雑誌）

68Ge/68Ga ジェネレータの長期間の品質検査　　　　　　　　　　　　　　　
富田 翔, 東川 桂, 上野 悟史, 水野 雄貴, 田沢 周作, 久下 裕司
核医学, 58, 1, 47, 58, 2021年06月, ［査読有り］

Determination of Brain Tumor Recurrence using 11 C‐methionine Positron Emission Tomography after Radiotherapy
Shigeru Yamaguchi, Kenji Hirata, Michinari Okamoto, Eku Shimosegawa, Jun Hatazawa, Ryuichi Hirayama, Naoki Kagawa, Haruhiko Kishima, Noboru Oriuchi, Masazumi Fujii, Kentaro Kobayashi, Hiroyuki Kobayashi, Shunsuke Terasaka, Ken‐ichi Nishijima, Yuji Kuge, Yoichi M Ito, Hiroshi Nishihara, Nagara Tamaki, Tohru Shiga
Cancer Science, 112, 10, 4246, 4256, 2021年06月, ［査読有り］
英語, 研究論文（学術雑誌）

Inhibition of xanthine oxidase in the acute phase of myocardial infarction prevents skeletal muscle abnormalities and exercise intolerance.
Hideo Nambu, Shingo Takada, Satoshi Maekawa, Junichi Matsumoto, Naoya Kakutani, Takaaki Furihata, Ryosuke Shirakawa, Takashi Katayama, Takayuki Nakajima, Katsuma Yamanashi, Yoshikuni Obata, Ippei Nakano, Masaya Tsuda, Akimichi Saito, Arata Fukushima, Takashi Yokota, Junko Nio-Kobayashi, Hironobu Yasui, Kei Higashikawa, Yuji Kuge, Toshihisa Anzai, Hisataka Sabe, Shintaro Kinugawa
Cardiovascular research, 117, 3, 805, 819, 2021年02月22日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, AIMS: Exercise intolerance in patients with heart failure (HF) is partly attributed to skeletal muscle abnormalities. We have shown that reactive oxygen species (ROS) play a crucial role in skeletal muscle abnormalities, but the pathogenic mechanism remains unclear. Xanthine oxidase (XO) is reported to be an important mediator of ROS overproduction in ischemic tissue. Here we tested the hypothesis that skeletal muscle abnormalities in HF are initially caused by XO-derived ROS and are prevented by the inhibition of their production. METHODS AND RESULTS: Myocardial infarction (MI) was induced in male C57BL/6J mice, which eventually led to HF, and a sham operation was performed in control mice. The time course of XO-derived ROS production in mouse skeletal muscle post-MI was first analyzed. XO-derived ROS production was significantly increased in MI mice from days 1 to 3 postsurgery (acute phase), whereas it did not differ between the MI and sham groups from 7 to 28 days (chronic phase). Second, mice were divided into three groups: sham+vehicle (Sham+Veh), MI+vehicle (MI+Veh), and MI+febuxostat (an XO inhibitor, 5 mg/kg body weight/day; MI+Feb). Febuxostat or vehicle was administered at 1 hr and 24 hr before surgery, and once-daily on days 1-7 postsurgery. On day 28 postsurgery, exercise capacity and mitochondrial respiration in skeletal muscle fibers were significantly decreased in MI+Veh compared with Sham+Veh mice. An increase in damaged mitochondria in MI+Veh compared with Sham+Veh mice was also observed. The wet weight and cross-sectional area of slow muscle fibers (higher XO-derived ROS) was reduced via the downregulation of protein synthesis-associated mTOR-p70S6K signaling in MI+Veh compared with Sham+Veh mice. These impairments were ameliorated in MI+Feb mice, in association with a reduction of XO-derived ROS production, without affecting cardiac function. CONCLUSIONS: XO inhibition during the acute phase post-MI can prevent skeletal muscle abnormalities and exercise intolerance in mice with HF. A TRANSLATIONAL PERSPECTIVE: We clearly demonstrated that febuxostat, an inhibitor of xanthine oxidase (XO), prevents exercise intolerance and skeletal muscle abnormalities (mitochondrial dysfunction and atrophy) via the suppression of XO-derived reactive oxygen species increase during hypoxia (e.g., myocardial infarction [MI]) in skeletal muscle during the early phase of heart failure (HF) model mouse. Our results shed light on the pathogenic mechanism of skeletal muscle abnormalities in HF after MI. The use of XO inhibitors requires consideration of the time course of XO activity. Our results indicate that the timing of administration is very important to achieve maximum beneficial effects when using XO inhibitors.

Transferrin-based radiolabeled probe predicts the sensitivity of human renal cancer cell lines to ferroptosis inducer erastin
Yuki Shibata, Hironobu Yasui, Kei Higashikawa, Yuji Kuge
Biochemistry and Biophysics Reports, 26, 100957, Elsevier BV, 2021年02月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Ferroptosis induction has been recognized as a novel cancer therapeutic strategy. To effectively apply ferroptosis-targeting cancer therapy to individual patients, a diagnostic indicator for selecting this therapeutic strategy from a number of molecular targeting drugs is needed. However, to date, methods that can predict the efficacy of ferroptosis-targeting treatment have not been established yet. In this study, we focused on the iron metabolic pathway to develop a nuclear imaging technique for diagnosing the susceptibility of cancer cells to ferroptosis. As a nuclear probe, human transferrin (Tf) was labeled with Gallium-68 (68Ga) using 2-(p-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) as a chelator (68Ga-NOTA-Tf). Western blot assay and clonogenic survival assay with human renal cancer cell lines A498 and 786-O revealed that the protein expression level of transferrin receptor1 (TfR1) and sensitivity to a ferroptosis inducer, erastin, were correlated. A cellular uptake assay with 68Ga-NOTA-Tf revealed that the cancer cells sensitive to erastin highly internalized the 68Ga-NOTA-Tf. Furthermore, treatment with the TfR1 inhibitor ferristatin II reduced the cellular uptake of 68Ga-NOTA-Tf, indicating that the intracellular uptake of the probe was mediated by TfR1. These results suggest that 68Ga-NOTA-Tf can be useful in predicting the sensitivity of cancer cells to ferroptosis inducers.

Preoperative Texture Analysis Using 11C-Methionine Positron Emission Tomography Predicts Survival after Surgery for Glioma
Osamu Manabe, Shigeru Yamaguchi, Kenji Hirata, Kentaro Kobayashi, Hiroyuki Kobayashi, Shunsuke Terasaka, Takuya Toyonaga, Keiichi Magota, Yuji Kuge, Nagara Tamaki, Tohru Shiga, Kohsuke Kudo
Diagnostics, 11, 2, 189, MDPI AG, 2021年01月28日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Background: Positron emission tomography with 11C-methionine (MET) is well established in the diagnostic work-up of malignant brain tumors. Texture analysis is a novel technique for extracting information regarding relationships among surrounding voxels, in order to quantify their inhomogeneity. This study evaluated whether the texture analysis of MET uptake has prognostic value for patients with glioma. Methods: We retrospectively analyzed adults with glioma who had undergone preoperative metabolic imaging at a single center. Tumors were delineated using a threshold of 1.3-fold of the mean standardized uptake value for the contralateral cortex, and then processed to calculate the texture features in glioma. Results: The study included 42 patients (median age: 56 years). The World Health Organization classifications were grade II (7 patients), grade III (17 patients), and grade IV (18 patients). Sixteen (16.1%) all-cause deaths were recorded during the median follow-up of 18.8 months. The univariate analyses revealed that overall survival (OS) was associated with age (hazard ratio (HR) 1.04, 95% confidence interval (CI) 1.01–1.08, p = 0.0093), tumor grade (HR 3.64, 95% CI 1.63–9.63, p = 0.0010), genetic status (p < 0.0001), low gray-level run emphasis (LGRE, calculated from the gray-level run-length matrix) (HR 2.30 × 1011, 95% CI 737.11–4.23 × 1019, p = 0.0096), and correlation (calculated from the gray-level co-occurrence matrix) (HR 5.17, 95% CI 1.07–20.93, p = 0.041). The multivariate analyses revealed OS was independently associated with LGRE and correlation. The survival curves were also significantly different (both log-rank p < 0.05). Conclusion: Textural features obtained using preoperative MET positron emission tomography may compliment the semi-quantitative assessment for prognostication in glioma cases.

Effects of feeding condition on the myocardial and hepatic accumulation of radioiodine-labeled BMIPP in mice
Kazuaki Yamasaki, Songji Zhao, Mie Nishimura, Yoichi Shimizu, Nagara Tamaki, Hiroshi Takeda, Yuji Kuge
Annals of Nuclear Medicine, 35, 1, 59, 64, Springer Science and Business Media LLC, 2021年01月, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）, OBJECTIVE: 123I-15-(p-iodophenyl)-3(R,S)-methylpentadecanoic acid ([123I]BMIPP), a fatty acid analog, is widely used for the diagnosis of cardiac diseases. Feeding condition is one of the important factors in the myocardial fatty acid uptake, which may also affect myocardial accumulation of [123I]BMIPP and image quality of [123I]BMIPP scintigraphy. However, the relationship between the myocardial accumulation of [123I]BMIPP and the feeding condition is not entirely clear. Therefore, we determined the myocardial accumulation of [125I]BMIPP in mice at various metabolic statuses induced by fasting in comparison with the hepatic accumulation. METHODS: Fed or fasted (6-, 12-, and 24-h fasted) mice were intravenously injected with [125I]BMIPP (35.2-75.0 kBq, 4 nmol). Radioactivities in the heart and liver were measured at 1, 5, 10, 30, 60, and 120 min after the injection (n = 5-15/time point for each group), and then, the heart-to-liver (H/L) ratios were calculated. RESULTS: The myocardial accumulation level of [125I]BMIPP in the fed group was almost the same as that in the 6-h-fasted group at each time point, although it was decreased by 12- and 24-h fasting. The H/L ratios of [125I]BMIPP accumulation level were significantly decreased by fasting (1.92 ± 0.22, 1.45 ± 0.13, 1.12 ± 0.13, and 0.91 ± 0.15 at 10 min, and 3.30 ± 0.62, 2.09 ± 0.35, 1.79 ± 0.34, and 1.27 ± 0.06 at 30 min after the injection, respectively, for the fed group and the 6-, 12-, and 24-h-fasted groups; p < 0.0001), largely owing to the increase in the hepatic accumulation level in the fasting groups. CONCLUSION: Although short-period (6 h) fasting did not affect the myocardial accumulation level of [125I]BMIPP, the hepatic accumulation level was increased. The present results indicate that the fed condition may provide higher-contrast images in myocardial [123I]BMIPP scintigraphy.

Decreased Proteasomal Function Induces Neuronal Loss and Memory Impairment
Utano Tomaru, Tomoki Ito, Yu Ohmura, Kei Higashikawa, Syota Miyajima, Ruka Tomatsu, Tsunehito Higashi, Akihiro Ishizu, Yuji Kuge, Mitsuhiro Yoshioka, Masanori Kasahara
The American Journal of Pathology, 191, 1, 144, 156, Elsevier BV, 2021年01月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Alzheimer disease (AD) is a progressive neurodegenerative disorder and the most common type of dementia worldwide. There is considerable evidence of age-related disruption of proteostasis being responsible for the development of AD. The proteasome is a multicatalytic enzyme complex that degrades both normal and damaged proteins, and an age-related decline in its activity has been implicated in age-related pathologies. Although proteasomal dysfunction is assumed to be a key AD hallmark, it remains unclear whether its role in disease onset is causative or secondary. In this study, we demonstrate that mice with proteasomal dysfunction exhibited memory impairment with associated neuronal loss, accumulation of phosphorylated tau, and activation of endoplasmic reticulum (ER) stress-related apoptosis pathways. Impaired proteasomal activity also activated ER stress-related apoptosis pathways in HT-22, a murine hippocampal neuronal cell line. HT-22 cell death, caused by proteasomal inhibition, was prevented by an inhibitor of c-Jun N-terminal kinase, an ER stress-related molecule. Collective evidence suggests that impaired proteasomal activity alters proteostasis, and subsequent ER stress-mediated pathways play pivotal roles in neuronal loss. Because aging decreases proteasomal function, age-related impairment of proteasomes may be involved in the development and progression of AD in elderly patients.

Increased [18F]FMISO accumulation under hypoxia by multidrug-resistant protein 1 inhibitors
Yoichi Shimizu, Yukihiro Nakai, Hiroyuki Watanabe, Shimpei Iikuni, Masahiro Ono, Hideo Saji, Yuji Kuge, Tsuneo Saga, Yuji Nakamoto
EJNMMI Research, 11, 1, 9, Springer Science and Business Media LLC, 2021年01月, ［査読有り］
研究論文（学術雑誌）,

[¹⁸F]Fluoromisonidazole ([¹⁸F]FMISO) is a PET imaging probe widely used for the detection of hypoxia. We previously reported that [¹⁸F]FMISO is metabolized to the glutathione conjugate of the reduced form in hypoxic cells. In addition, we found that the [¹⁸F]FMISO uptake level varied depending on the cellular glutathione conjugation and excretion ability such as enzyme activity of glutathione-S-transferase and expression levels of multidrug resistance-associated protein 1 (MRP1, an efflux transporter), in addition to the cellular hypoxic state. In this study, we evaluated whether MRP1 activity affected [¹⁸F]FMISO PET imaging.




FaDu human pharyngeal squamous cell carcinoma cells were pretreated with MRP1 inhibitors (cyclosporine A, lapatinib, or MK-571) for 1 h, incubated with [¹⁸F]FMISO for 4 h under hypoxia, and their radioactivity was then measured. FaDu tumor-bearing mice were intravenously injected with [¹⁸F]FMISO, and PET/CT images were acquired at 4 h post-injection (1st PET scan). Two days later, the same mice were pretreated with MRP1 inhibitors (cyclosporine A, lapatinib, or MK-571) for 1 h, and PET/CT images were acquired (2nd PET scan).




FaDu cells pretreated with MRP1 inhibitors exhibited significantly higher radioactivity than those without inhibitor treatment (cyclosporine A: 6.91 ± 0.27, lapatinib: 10.03 ± 0.47, MK-571: 10.15 ± 0.44%dose/mg protein, p < 0.01). In the in vivo PET study, the SUV_mean ratio in tumors [calculated as after treatment (2nd PET scan)/before treatment of MRP1 inhibitors (1st PET scan)] of the mice treated with MRP1 inhibitors was significantly higher than those of control mice (cyclosporine A: 2.6 ± 0.7, lapatinib: 2.2 ± 0.7, MK-571: 2.2 ± 0.7, control: 1.2 ± 0.2, p < 0.05).




In this study, we revealed that MRP1 inhibitors increase [¹⁸F]FMISO accumulation in hypoxic cells. This suggests that [¹⁸F]FMISO-PET imaging is affected by MRP1 inhibitors independent of the hypoxic state.

Characterization of brown adipose tissue thermogenesis in the naked mole-rat (Heterocephalus glaber), a heterothermic mammal
Yuki Oiwa, Kaori Oka, Hironobu Yasui, Kei Higashikawa, Hidemasa Bono, Yoshimi Kawamura, Shingo Miyawaki, Akiyuki Watarai, Takefumi Kikusui, Atsushi Shimizu, Hideyuki Okano, Yuji Kuge, Kazuhiro Kimura, Yuko Okamatsu-Ogura, Kyoko Miura
Scientific Reports, 10, 1, 19488, Springer Science and Business Media LLC, 2020年12月, ［査読有り］
研究論文（学術雑誌）,
The naked mole-rat (NMR) is a heterothermic mammal that forms eusocial colonies consisting of one reproductive female (queen), several reproductive males, and subordinates. Despite their heterothermy, NMRs possess brown adipose tissue (BAT), which generally induces thermogenesis in cold and some non-cold environments. Previous studies suggest that NMR-BAT induces thermogenesis by cold exposure. However, detailed NMR-BAT characteristics and whether NMR-BAT thermogenesis occurs in non-cold environments are unknown. Here, we show beta-3 adrenergic receptor (ADRB3)-dependent thermogenic potential of NMR-BAT, which contributes to thermogenesis in the isolated queen in non-cold environments (30 °C). NMR-BAT expressed several brown adipocyte marker genes and showed noradrenaline-dependent thermogenic activity in vitro and in vivo. Although our ADRB3 inhibition experiments revealed that NMR-BAT thermogenesis slightly delays the decrease in body temperature in a cold environment (20 °C), it was insufficient to prevent the decrease in the body temperatures. Even at 30 °C, NMRs are known to prevent the decrease of and maintain their body temperature by heat-sharing behaviors within the colony. However, isolated NMRs maintained their body temperature at the same level as when they are in the colony. Interestingly, we found that queens, but not subordinates, induce BAT thermogenesis in this condition. Our research provides novel insights into NMR thermoregulation.

Influence of the scan time point when assessing hypoxia in 18F-fluoromisonidazole PET: 2 vs. 4 h.
Kentaro Kobayashi, Osamu Manabe, Kenji Hirata, Shigeru Yamaguchi, Hiroyuki Kobayashi, Shunsuke Terasaka, Takuya Toyonaga, Sho Furuya, Keiichi Magota, Yuji Kuge, Kohsuke Kudo, Tohru Shiga, Nagara Tamaki
European journal of nuclear medicine and molecular imaging, 47, 8, 1833, 1842, 2020年07月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, PURPOSE: 18F-fluoromisonidazole (18F-FMISO) is the most widely used positron emission tomography (PET) tracer for imaging tumor hypoxia. Previous reports suggested that the time from injection to the scan may affect the assessment of 18F-FMISO uptake. Herein, we directly compared the images at 2 h and 4 h after a single injection of 18F-FMISO. METHODS: Twenty-three patients with or suspected of having a brain tumor were scanned twice at 2 and 4 h following an intravenous injection of 18F-FMISO. We estimated the mean standardized uptake value (SUV) of the gray matter and white matter and the gray-to-white matter ratio in the background brain tissue from the two scans. We also performed a semi-quantitative analysis using the SUVmax and maximum tumor-to-normal ratio (TNR) for the tumor. RESULTS: At 2 h, the SUVmean of gray matter was significantly higher than that of white matter (median 1.23, interquartile range (IQR) 1.10-1.32 vs. 1.04, IQR 0.95-1.16, p < 0.0001), whereas at 4 h, it significantly decreased to approach that of the white matter (1.10, IQR 1.00-1.23 vs. 1.02, IQR 0.93-1.13, p = NS). The gray-to-white matter ratio thus significantly declined from 1.17 (IQR 1.14-1.19) to 1.09 (IQR 1.07-1.10) (p < 0.0001). All 7 patients with glioblastoma showed significant increases in the SUVmax (2.20, IQR 1.67-3.32 at 2 h vs. 2.65, IQR 1.74-4.41 at 4 h, p = 0.016) and the TNR (1.75, IQR 1.40-2.38 at 2 h vs. 2.34, IQR 1.67-3.60 at 4 h, p = 0.016). CONCLUSION: In the assessment of hypoxic tumors, 18F-FMISO PET for hypoxia imaging should be obtained at 4 h rather than 2 h after the injection.

Association of Hydrophobic Carboxyl-Terminal Dendrimers with Lymph Node-Resident Lymphocytes.
Yutaka Nishimoto, Misaki Nishio, Shu Nagashima, Kohei Nakajima, Takayuki Ohira, Shinya Nakai, Ikuhiko Nakase, Kei Higashikawa, Yuji Kuge, Akikazu Matsumoto, Mikako Ogawa, Chie Kojima
Polymers, 12, 7, 2020年06月30日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Delivery systems to lymph node-resident T cells around tumor tissues are essential for cancer immunotherapy, in order to boost the immune responses. We previously reported that anionic dendrimers, such as carboxyl-, sulfonyl-, and phosphate-terminal dendrimers, were efficiently accumulated in lymph nodes via the intradermal injection. Depending on the terminal structure, their cell association properties were different, and the carboxyl-terminal dendrimers did not associate with any immune cells majorly. In this study, we investigated the delivery of carboxyl-terminal dendrimers with different hydrophobicity to lymph node-resident lymphocytes. Four types of carboxyl-terminal dendrimers-succinylated (C) and 2-carboxy-cyclohexanoylated (Chex) dendrimers with and without phenylalanine (Phe)-were synthesized and named C-den, C-Phe-den, Chex-den, and Chex-Phe-den, respectively. Chex-Phe-den was well associated with lymphocytes, but others were not. Chex-Phe-den, intradermally injected at the footpads of mice, was accumulated in the lymph node, and was highly associated with the lymphocytes, including T cells. Our results suggest that Chex-Phe-den has the potential for delivery to the lymph node-resident T cells, without any specific T cell-targeted ligands.

Biodistribution and internal radiation dosimetry of a novel probe for thymidine phosphorylase imaging, [123I]IIMU, in healthy volunteers.
Shiro Watanabe, Ken-Ichi Nishijima, Shozo Okamoto, Keiichi Magota, Kenji Hirata, Takuya Toyonaga, Tohru Shiga, Yuji Kuge, Nagara Tamaki
Annals of nuclear medicine, 34, 8, 595, 599, 2020年05月02日, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）, OBJECTIVE: We evaluated the radiation dosage, biodistribution, human safety, and tolerability of the injection of a single dose of [123I] 5-iodo-6-[ (2-iminoimidazolidinyl)methyl]uracil (IIMU), a new radiotracer targeting thymidine phosphorylase (TP), in healthy volunteers. METHODS: Potential participants were tested at our hospital to confirm their eligibility. Two healthy male adults passed the screening tests. They were injected with 56 and 111 MBq of [123I]IIMU, respectively. Safety assessments were performed before and at 1, 3, 6, 9, 24, 48 h, and 1-week post-injection. Whole-body emission scans were conducted at 1, 3, 6, 24, and 48 h post-injection. Regions of interest were manually drawn to enclose the entire body at each time point, identifying high-uptake organs to obtain the time-activity curves. Urine and blood samples were collected at 1, 2, 3, 4, 5, 6, 9, 24, and 48 h post-injection. The radiation dose for each organ and the effective doses were estimated using OLINDA/EXM 1.1 software. RESULTS: No adverse events were observed as of the follow-up visit > 1-week post-injection. In both subjects, the highest uptake of [123I]IIMU occurred in the liver, with peak injected activity (%IA) values of 17.7% and 15.1%, respectively. The second highest uptake was in the thyroid (0.35% and 0.66% IA). The %IA decreased gradually toward the end of the study (48 h) in all organs except the liver and thyroid. By the end of the study, 52.5% and 51.5% of the injected activity of [123I]IIMU had been excreted via the subjects' renal systems. The estimated mean effective doses of [123I]IIMU were 9.19 μSv/MBq and 10.1 μSv/MBq, respectively. CONCLUSION: In this preliminary study, [123I]IIMU was safely administered to healthy adults, and its potential clinical use in TP imaging was revealed.

Influence on [18F]FDG uptake by cancer cells after anti-PD-1 therapy in an enforced-immune activated mouse tumor.
Mayu Tomita, Motofumi Suzuki, Yusuke Kono, Kohei Nakajima, Takuma Matsuda, Yuji Kuge, Mikako Ogawa
EJNMMI research, 10, 1, 24, 24, 2020年03月19日, ［査読有り］, ［国際誌］
英語, BACKGROUND: Anti-programmed cell death 1 (PD-1) antibody is an immune checkpoint inhibitor, and anti-PD-1 therapy improves the anti-tumor functions of T cells and affects tumor microenvironment. We previously reported that anti-PD-1 treatment affected tumor glycolysis by using 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography (PET). That study showed that anti-PD-1 therapy in a mouse B16F10 melanoma model increased glucose metabolism in cancer cells at the point where anti-PD-1 therapy did not cause a significant inhibition of tumor growth. However, the B16F10 melanoma model is poorly immunogenic, so it is not clear how anti-PD-1 treatment affects glucose metabolism in highly immunogenic cancer models. In this study, we used a cyclic dinucleotide GMP-AMP (cGAMP)-injected B16F10 melanoma model to investigate the effect of anti-PD-1 therapy on [18F]FDG uptake in a highly immune activated tumor in mice. RESULTS: To compare the cGAMP-injected B16F10 model with the B16F10 model, experiments were performed as described in our previous manuscript. [18F]FDG-PET was measured before treatment and 7 days after the start of treatment. In this study, [18F]FDG uptake in tumors in the cGAMP/anti-PD-1 combination group was lower than that in the anti-PD-1 treatment group tumors on day 7, as shown by PET and ex vivo validation. Flow-cytometry was performed to assess immune cell populations and glucose metabolism. Anti-PD-1 and/or cGAMP treatment increased the infiltration level of immune cells into tumors. The cGAMP/anti-PD-1 combination group had significantly lower levels of GLUT1high cells/hexokinase IIhigh cells in CD45- cancer cells compared with tumors in the anti-PD-1 treated group. These results suggested that if immune responses in tumors are higher than a certain level, glucose uptake in cancer cells is reduced depending on that level. Such a change of glucose uptake might be caused by the difference in infiltration or activation level of immune cells between the anti-PD-1 treated group and the cGAMP/anti-PD-1 combination group. CONCLUSIONS: [18F]FDG uptake in cancer cells after anti-PD-1 treatment might be affected by the tumor immune microenvironment including immune cell infiltration, composition, and activation status.

FTY720 Protects Against Ischemia-Reperfusion Injury by Preventing the Redistribution of Tight Junction Proteins and Decreases Inflammation in the Subacute Phase in an Experimental Stroke Model.
Zifeng Wang, Kei Higashikawa, Hironobu Yasui, Yuji Kuge, Yusuke Ohno, Akio Kihara, Yenari A Midori, Kiyohiro Houkin, Masahito Kawabori
Translational stroke research, 11, 5, 1103, 1116, 2020年02月27日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Injury due to brain ischemia followed by reperfusion (I/R) may be an important therapeutic target in the era of thrombectomy. FTY720, a widely known sphingosine-1-phosphate receptor agonist, exerts various neuroprotective effects. The aim of this study was to examine the protective effect of FTY720 with respect to I/R injury, especially focusing on blood-brain barrier (BBB) protection and anti-inflammatory effects. Male rats were subjected to transient ischemia and administered vehicle or 0.5 or 1.5 mg/kg of FTY720 immediately before reperfusion. Positron emission tomography (PET) with [18F]DPA-714 was performed 2 and 9 days after the insult to serially monitor neuroinflammation. Bovine and rat brain microvascular endothelial cells (MVECs) were also subjected to oxygen-glucose deprivation (OGD) and reperfusion, and administered FTY720, phosphorylated-FTY720 (FTY720-P), or their inhibitor. FTY720 dose-dependently reduced cell death, the infarct size, cell death including apoptosis, and inflammation. It also ameliorated BBB disruption and neurological deficits compared to in the vehicle group. PET indicated that FTY720 significantly inhibited the worsening of inflammation in later stages. FTY720-P significantly prevented the intracellular redistribution of tight junction proteins but did not increase their mRNA expression. These results suggest that FTY720 can ameliorate I/R injury by protecting the BBB and regulating neuroinflammation.

Carboxyl-, sulfonyl-, and phosphate-terminal dendrimers as a nanoplatform with lymph node targeting　　　　　　　　　　　　　　　
Nishimoto Y, Nagashima S, Nakajima K, Ohira T, Sato T, Izawa T, Yamate J, Higashikawa K, Kuge Y, Ogawa M, Kojima C
Int J Pharm., 576, 119021, 2020年, ［査読有り］
英語

Preclinical investigation of potential use of thymidine phosphorylase-targeting tracer for diagnosis of nonalcoholic steatohepatitis.
Higashikawa K, Horiguchi S, Tarisawa M, Shibata Y, Ohkura K, Yasui H, Takeda H, Kuge Y
Nuclear medicine and biology, 82-83, 25, 32, 2019年12月16日, ［査読有り］, ［国際誌］
英語, INTRODUCTION: Although liver biopsy is the gold standard for the diagnosis of nonalcoholic steatohepatitis (NASH), it has several problems including high invasiveness and sampling errors. Therefore, the development of alternative methods to overcome these disadvantages is strongly required. In this study, we evaluated the potential use of our tracer targeting thymidine phosphorylase (TYMP), 5-[123I]iodo-6-[ (2-iminoimidazolidinyl)methyl]uracil ([123I]IIMU) for the diagnosis of NASH. METHODS: The mice used as the NASH model (hereafter, NASH mice) were prepared by feeding a methionine- and choline-deficient diet for 4 weeks. A control group was similarly given a control diet. The expression levels of the TYMP gene and protein in the liver were examined by real-time reverse-transcription polymerase chain reaction and western blot analyses. The localizations of [125I]IIMU and the TYMP protein in the liver were examined by autoradiography and immunohistochemical staining, respectively. Finally, the mice were injected with [123I]IIMU and single-photon emission tomography (SPECT) imaging was conducted. RESULTS: The hepatic expression levels of TYMP were significantly lower in the NASH mice than in the control mice at both mRNA and protein levels, suggesting that a decrease in TYMP level could be an indicator of NASH. [125I]IIMU was uniformly distributed in the liver of the control mice, whereas it showed a patchy distribution in that of the NASH mice. The localization of [125I]IIMU was visually consistent with that of the TYMP protein in the liver of the control and NASH mice. SPECT analysis indicated that the hepatic accumulation of [123I]IIMU in the NASH mice was significantly lower than that in the control mice [SUV (g/ml): 4.14 ± 0.87 (Control) vs 2.31 ± 0.29 (NASH)]. CONCLUSIONS: [123I]IIMU may provide a noninvasive means for imaging TYMP expression in the liver and may be applicable to the diagnosis of NASH.

18F-FMISO PET/CT detects hypoxic lesions of cardiac and extra-cardiac involvement in patients with sarcoidosis.
Sho Furuya, Masanao Naya, Osamu Manabe, Kenji Hirata, Hiroshi Ohira, Tadao Aikawa, Kazuhiro Koyanagawa, Keiichi Magota, Ichizo Tsujino, Toshihisa Anzai, Yuji Kuge, Noriko Oyama-Manabe, Kohsuke Kudo, Tohru Shiga, Nagara Tamaki
Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology, 2019年12月09日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: 18F-fluoromisonidazole (FMISO) is a hypoxia positron emission tomography (PET) tracer. Here, we evaluated cardiac and extra-cardiac sarcoidosis using both FMISO and 18F-fluorodeoxyglucose (FDG) PET/CT in a prospective cohort of patients with sarcoidosis. METHODS: Ten consecutive sarcoidosis patients with suspected cardiac involvement were prospectively enrolled. Each patient fasted overnight (for ≥ 18 hours) preceded by a low-carbohydrate diet before FDG PET/CT but not given special dietary instructions before the FMISO PET/CT scan. We visually and semiquantitatively assessed the uptakes of FMISO and FDG using the maximal standardized uptake value (SUVmax). The metabolic volume (MV) of FDG was calculated as the volume within the boundary determined by the threshold (mean SUV of blood pool × 1.5). RESULTS: Nine patients showed focal FDG uptake in the myocardium and were diagnosed with cardiac sarcoidosis. Among the patients with extra-cardiac lesions, FDG uptake was seen in 8 lymph nodes and 3 lung lesions. FMISO uptake was seen in the 7 cardiac (77.8%) and 6 extra-cardiac (54.5%) lesions. None of the patients showed physiological FMISO uptake in the myocardium. The SUVmax values of the lesions with FMISO uptake were higher than those of the lesions without FMISO uptake in both the cardiac (SUVmax: 9.9, IQR: 8.4-10.0 vs 7.3, IQR: 6.3-8.2) and non-cardiac lesions (SUVmax: 17.6, IQR: 14.5-19.3 vs 6.1, IQR: 5.9-6.2; P = 0.006). The MV values of the lesions with FMISO uptake were significantly higher than those of the lesions without FMISO uptake (111.3, IQR: 78.3-135.7 vs 6.4, IQR: 1.9-23.3; P = 0.0009). CONCLUSIONS: FMISO showed no physiological myocardial uptake and did not require special preparation. FMISO PET has the potential to detect hypoxic lesions in patients with sarcoidosis.

Combination of FDG-PET and FMISO-PET as a treatment strategy for patients undergoing early-stage NSCLC stereotactic radiotherapy.
Shiro Watanabe, Tetsuya Inoue, Shozo Okamoto, Keiichi Magota, Ayumi Takayanagi, Jun Sakakibara-Konishi, Norio Katoh, Kenji Hirata, Osamu Manabe, Takuya Toyonaga, Yuji Kuge, Hiroki Shirato, Nagara Tamaki, Tohru Shiga
EJNMMI research, 9, 1, 104, 2019年12月04日, ［査読有り］, ［国際誌］
英語, BACKGROUND: We investigated the prognostic predictive value of the combination of fluorodeoxyglucose (FDG)- and fluoromisonidazole (FMISO)-PET in patients with non-small cell lung carcinoma (NSCLC) treated with stereotactic body radiation therapy (SBRT). PATIENTS AND METHODS: We prospectively examined patients with pathologically proven NSCLC; all underwent FDG and FMISO PET/CT scans before SBRT. PET images were acquired using a whole-body time-of-flight PET-CT scanner with respiratory gating. We classified them into recurrent and non-recurrent groups based on their clinical follow-ups and compared the groups' tumor diameters and PET parameters (i.e., maximum of the standardized uptake value (SUVmax), metabolic tumor volume, tumor-to-muscle ratio, and tumor-to-blood ratio). We performed univariate analysis to evaluate the impact of the PET variables on the patients' progression-free survival (PFS). We divided the patients by thresholds of FDG SUVmax and FMISO SUVmax obtained from receiver operating characteristic analysis for assessment of recurrence rate and PFS. RESULTS: Thirty-two NSCLC patients (19 male and 13 females; median age, 83 years) were enrolled. All received SBRT. At the study endpoint, 23 patients (71.9%) were non-recurrent and nine patients (28.1%) had recurrent disease. Significant between-group differences were observed in tumor diameter and all the PET parameters, demonstrating that those were significant predictors of the recurrence in all patients. In the 22 patients with tumors > 2 cm, tumor diameter and FDG SUVmax were not significant predictors. Thirty-two patients were divided into three patterns from the thresholds of FDG SUVmax (6.81) and FMISO SUVmax (1.89); A, low FDG and low FMISO (n = 14); B, high FDG and low FMISO (n = 8); C, high FDG and high FMISO (n = 10). No pattern A patient experienced tumor recurrence, whereas two pattern B patients (25%) and seven pattern C patients (70%) exhibited recurrence. A Kaplan-Meier analysis of all patients revealed a significant difference in PFS between patterns A and B (p = 0.013) and between patterns A and C (p < 0.001). In the tumors > 2 cm patients, significant differences in PFS were demonstrated between pattern A and C patients (p = 0.002). CONCLUSION: The combination of FDG- and FMISO-PET can identify patients with a baseline risk of recurrence and indicate whether additional therapy might be performed to improve survival.

Biodistribution and radiation dosimetry of the novel hypoxia PET probe [18F]DiFA and comparison with [18F]FMISO.
Shiro Watanabe, Tohru Shiga, Kenji Hirata, Keiichi Magota, Shozo Okamoto, Takuya Toyonaga, Kei Higashikawa, Hironobu Yasui, Jun Kobayashi, Ken-Ichi Nishijima, Ken Iseki, Hiroki Matsumoto, Yuji Kuge, Nagara Tamaki
EJNMMI research, 9, 1, 60, 60, 2019年07月05日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: To facilitate hypoxia imaging in a clinical setting, we developed 1-(2,2-dihydroxymethyl-3-[18F]-fluoropropyl)-2-nitroimidazole ([18F]DiFA) as a new tracer that targets tumor hypoxia with its lower lipophilicity and efficient radiosynthesis. Here, we evaluated the radiation dosage, biodistribution, human safety, tolerability, and early elimination after the injection of [18F]DiFA in healthy subjects, and we performed a preliminary clinical study of patients with malignant tumors in a comparison with [18F]fluoromisonidazole ([18F]FMISO). RESULTS: The single administration of [18F]DiFA in 8 healthy male adults caused neither adverse events nor abnormal clinical findings. Dynamic and sequential whole-body scans showed that [18F]DiFA was rapidly cleared from all of the organs via the hepatobiliary and urinary systems. The whole-body mean effective dose of [18F]DiFA estimated by using the medical internal radiation dose (MIRD) schema with organ level internal dose assessment/exponential modeling (OLINDA/EXM) computer software 1.1 was 14.4 ± 0.7 μSv/MBq. Among the organs, the urinary bladder received the largest absorbed dose (94.7 ± 13.6 μSv/MBq). The mean absorbed doses of the other organs were equal to or less than those from other hypoxia tracers. The excretion of radioactivity via the urinary system was very rapid, reaching 86.4 ± 7.1% of the administered dose. For the preliminary clinical study, seven patients were subjected to [18F]FMISO and [18F]DiFA positron emission tomography (PET) at 48-h intervals to compare the two tracers' diagnostic ability for tumor hypoxia. The results of the tumor hypoxia evaluation by [18F]DiFA PET at 1 h and 2 h were not significantly different from those obtained with [18F]FMISO PET at 4 h ([18F]DiFA at 1 h, p = 0.32; [18F]DiFA at 2 h, p = 0.08). Moreover, [18F]DiFA PET at both 1 h (k = 0.68) and 2 h (k = 1.00) showed better inter-observer reproducibility than [18F]FMISO PET at 4 h (k = 0.59). CONCLUSION: [18F]DiFA is well tolerated, and its radiation dose is comparable to those of other hypoxia tracers. [18F]DiFA is very rapidly cleared via the urinary system. [18F]DiFA PET generated comparable images to [18F]FMISO PET in hypoxia imaging with shorter waiting time, demonstrating the promising potential of [18F]DiFA PET for hypoxia imaging and for a multicenter trial.

Elimination of tumor hypoxia by eribulin demonstrated by 18F-FMISO hypoxia imaging in human tumor xenograft models.
Songji Zhao, Wenwen Yu, Naoyuki Ukon, Chengbo Tan, Ken-Ichi Nishijima, Yoichi Shimizu, Kei Higashikawa, Tohru Shiga, Hiroko Yamashita, Nagara Tamaki, Yuji Kuge
EJNMMI research, 9, 1, 51, 51, 2019年06月03日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Eribulin, an inhibitor of microtubule dynamics, shows antitumor potency against a variety of solid cancers through its antivascular activity and remodeling of tumor vasculature. 18F-Fluoromisonidazole (18F-FMISO) is the most widely used PET probe for imaging tumor hypoxia. In this study, we utilized 18F-FMISO to clarify the effects of eribulin on the tumor hypoxic condition in comparison with histological findings. MATERIAL AND METHODS: Mice bearing a human cancer cell xenograft were intraperitoneally administered a single dose of eribulin (0.3 or 1.0 mg/kg) or saline. Three days after the treatment, mice were injected with 18F-FMISO and pimonidazole (hypoxia marker for immunohistochemistry), and intertumoral 18F-FMISO accumulation levels and histological characteristics were determined. PET/CT was performed pre- and post-treatment with eribulin (0.3 mg/kg, i.p.). RESULTS: The 18F-FMISO accumulation levels and percent pimonidazole-positive hypoxic area were significantly lower, whereas the number of microvessels was higher in the tumors treated with eribulin. The PET/CT confirmed that 18F-FMISO distribution in the tumor was decreased after the eribulin treatment. CONCLUSIONS: Using 18F-FMISO, we demonstrated the elimination of the tumor hypoxic condition by eribulin treatment, concomitantly with the increase in microvessel density. These findings indicate that PET imaging using 18F-FMISO may provide the possibility to detect the early treatment response in clinical patients undergoing eribulin treatment.

Comparative evaluation of [18F]DiFA and its analogs as novel hypoxia positron emission tomography and [18F]FMISO as the standard.
Norihito Nakata, Masato Kiriu, Yuki Okumura, Songji Zhao, Ken-Ichi Nishijima, Tohru Shiga, Nagara Tamaki, Yuji Kuge, Hiroki Matsumoto
Nuclear medicine and biology, 70, 39, 45, 2019年03月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, INTRODUCTION: Hypoxia, a common feature of most solid tumors, is an important predictor of tumor progression and resistance to radiotherapy. We developed a novel hypoxia imaging probe with optimal biological characteristics for use in clinical settings. METHODS: We designed and synthesized several new hypoxia probes with additional hydrophilic characteristics compared to [18F]fluoromisonidazole ([18F]FMISO). These were 1-(2,2-Dihydroxy-methyl-3-[18F]-Fluoropropyl) azomycin ([18F]DiFA, formerly [18F]HIC101) and its analogs ([18F]F1 and [18F]F2). Biodistribution studies with EMT6 mammary carcinoma cell-bearing mice were performed 1 and 2 h after injection of each probe. Small-animal positron emission tomography (PET) imaging studies were conducted using [18F]DiFA and [18F]FMISO in the same mice. Tumoral hypoxia was confirmed via pimonidazole staining. Ex vivo digital autoradiographs were obtained for confirming the co-localization of [18F]DiFA and pimonidazole in the tumor tissues. RESULTS: The EMT6 tumors used had pimonidazole-positive regions. In biodistribution studies, the tumor-to-blood ratio and tumor-to-muscle ratio of [18F]DiFA was significantly higher than the respective [18F]FMISO ratios 1 h after injection. Hence, we selected [18F]DiFA as the best hypoxia probe among those tested. Small-animal PET imaging studies showed time-dependent increases in the tumor-to-normal tissue ratio of [18F]DiFA uptake. Rapid clearance from the rest of the body was observed primarily via the renal system. Ex vivo autoradiography showed a positive correlation between [18F]DiFA uptake and the regions of pimonidazole distribution, indicating that [18F]DiFA selectively accumulated in the tumor tissue's hypoxic region. CONCLUSIONS: A better contrast image and a shorter waiting time may be obtained with [18F]DiFA than with [18F]FMISO. ADVANCES IN KNOWLEDGE: By optimizing LogP based on the [18F]FMISO structure, we demonstrated that [18F]DiFA could detect tumor hypoxia regions at an early time point. IMPLICATIONS FOR PATIENT CARE: [18F]DiFA imaging facilitates the evaluation of various cancer hypoxic states due to the lower uptake of normal tissues and could contribute to novel treatment development.

A novel PET probe “[18F]DiFA” accumulates in hypoxic region via glutathione conjugation following reductive metabolism.
Shimizu Y, Zhao S, Yasui H, Nishijima K, Matsumoto H, Shiga T, Tamaki N, Ogawa M, Kuge Y
Mol Imaging Biol, 21, 1, 122, 129, 2019年02月, ［査読有り］, ［国際誌］
英語, PURPOSE: Hypoxia in tumor has close relationship with angiogenesis and tumor progression. Previously, we developed 2,2-dihydroxymethyl-3-[18F]fluoropropyl-2-nitroimidazole ([18F]DiFA) as a novel positron emission tomography (PET) probe for diagnosis of hypoxia. In this study, we elucidated whether the accumulation of [18F]DiFA in cells is dependent on the hypoxic state and revealed how [18F]DiFA accumulates in hypoxic cells in combination with imaging mass spectrometry (IMS). PROCEDURES: FaDu human head and neck cancer cells were treated with [18F]DiFA and then incubated under normoxia (21% O2) or hypoxia (1% O2) for 2 h. The cells were extracted using methanol, and the radioactivities of the precipitates (macromolecule fraction) and supernatants (low-molecular-weight fraction) were measured. FaDu-bearing mice were injected intravenously with [18F]DiFA and with pimonidazole 1 h later. The tumors were excised 2 h after the injection of [18F]DiFA. Autoradiography, IMS, and immunohistochemical (IHC) staining for pimonidazole were performed with serial tumor sections. RESULTS: In the in vitro study, the radioactivity of FaDu cells was significantly higher under hypoxia than that under normoxia (0.53 ± 0.02 vs. 0.27 ± 0.02 %dose/mg protein, p < 0.05). The radioactivity of the low-molecular-weight fraction was 66.3 ± 0.6% in the hypoxic cell. In the in vivo study, [18F]DiFA accumulated in the tumor tissues existed mainly as low-molecular-weight compounds (90.4 ± 0.9%). In addition, the glutathione conjugate of reductive DiFA metabolite (amino-DiFA-GS) existed in tumor tissues revealed by the IMS study, and the distribution pattern of amino-DiFA-GS was very similar to that of the radioactivity and the positive staining area of pimonidazole. CONCLUSIONS: Our results suggest that [18F]DiFA undergoes the glutathione conjugation reaction following reductive metabolism in hypoxic cells, which leads hypoxia-specific PET imaging with [18F]DiFA.

Erastin, a ferroptosis-inducing agent, sensitized cancer cells to X-ray irradiation via glutathione starvation in vitro and in vivo.
Shibata Y, Yasui H, Higashikawa K, Miyamoto N, Kuge Y
PloS one, 14, 12, e0225931, 2019年, ［査読有り］

Glutathione and cysteines suppress cytotoxicity of gas phase of cigarette smoke by direct reacting with unsaturated carbonyl compounds in the gas phase.
Higashi T, Elmeligy E, Mai Y, Noya Y, Terada K, Mazaki Y, Kuge Y, Miwa S
Biochem Biophys Res Commun., 509, 4, 988, 993, 2019年, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Unsaturated carbonyl compounds, such as acrolein (ACR) and methyl vinyl ketone (MVK), are environmental pollutants, and are contained in smoke, automobile exhaust, and heated oil. We have previously reported that major cytotoxic factors in the gas phase of cigarette smoke are ACR and MVK. ACR and MVK induce cell damage by reactive oxygen species generation via protein kinase C and NADPH oxidases, and antioxidants, such as glutathione (GSH) and N-acetylcysteine (NAC), can effectively suppress their cytotoxic activities. In this study, we attempted to elucidate the molecular mechanism(s) for suppression of ACR- and MVK-induced cytotoxic activities by these antioxidants. GSH, NAC, L- and D-cysteines completely suppressed cell damage induced by gas phase extract of cigarette smoke. The results of HPLC and mass spectrometry showed that GSH and NAC directly reacted with ACR and MVK. Cysteines and cysteine derivatives suppressed ACR-induced GAPDH carbonylation, a representative protein for carbonylation. The current results suggest that GSH, NAC, and cysteines directly reacted with ACR and MVK, and suppressed these unsaturated carbonyl compounds-induced cell damage by inhibition of protein carbonylation.

Voxel based comparison and texture analysis of 18F-FDG and 18F-FMISO PET of patients with head-and-neck cancer.
Kroenke M, Hirata K, Gafita A, Watanabe S, Okamoto S, Magota K, Shiga T, Kuge Y, Tamaki N
PLoS One, 14, 2, e0213111, 2019年, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Hypoxia can induce radiation resistance and is an independent prognostic marker for outcome in head and neck cancer. As 18F-FMISO (FMISO), a hypoxia tracer for PET, is far less common than 18F-FDG (FDG) and two separate PET scans result in doubled cost and radiation exposure to the patient, we aimed to predict hypoxia from FDG PET with new techniques of voxel based analysis and texture analysis. METHODS: Thirty-eight patients with head-and-neck cancer underwent consecutive FDG and FMISO PET scans before any treatment. ROIs enclosing the primary cancer were compared in a voxel-by-voxel manner between FDG and FMISO PET. Tumour hypoxia was defined as the volume with a tumour-to-muscle ratio (TMR) > 1.25 in the FMISO PET and hypermetabolic volume was defined as >50% SUVmax in the FDG PET. The concordance rate was defined as percentage of voxels within the tumour which were both hypermetabolic and hypoxic. 38 different texture analysis (TA) parameters were computed based on the ROIs and correlated with presence of hypoxia. RESULTS: Within the hypoxic tumour regions, the FDG uptake was twice as high as in the non-hypoxic tumour regions (SUVmean 10.9 vs. 5.4; p<0.001). A moderate correlation between FDG and FMISO uptake was found by a voxel-by-voxel comparison (r = 0.664 p<0.001). The average concordance rate was 25% (± 22%). Entropy was the TA parameter showing the highest correlation with hypoxia (r = 0.524 p<0.001). CONCLUSION: FDG uptake was higher in hypoxic tumour regions than in non-hypoxic regions as expected by tumour biology. A moderate correlation between FDG and FMISO PET was found by voxel-based analysis. TA yielded similar results in FDG and FMISO PET. However, it may not be possible to predict tumour hypoxia even with the help of texture analysis.

Accumulation of hypoxia imaging probe "18F-FMISO" in macrophages depends on macrophage polarization in addition to hypoxic state.
Shimizu Y, Motomura A, Takakura H, Tamaki N, Kuge Y, Ogawa M
Ann Nucl Med., 33, 5, 362, 367, 2019年, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）, OBJECTIVE: Macrophages play an essential role in immune response, and are closely related to the progression of diseases such as cancer and atherosclerosis. Macrophages polarize to M1 or M2 type, which is related to the environmental hypoxic state. Previously, we found that 18F-FMISO uptake varied according to expression levels of biomolecules such as glutathione S-transferase P1 (GST-P1), which catalyzes the conjugation of glutathione to 18F-FMISO metabolites, and multidrug resistance-associated protein 1 (MRP1), which exports glutathione-18F-FMISO metabolite conjugates out of cells. However, the relationship between macrophage polarization and 18F-FMISO accumulation remains unclear. METHODS: Mouse peritoneal macrophages were polarized to either the M1 or M2 type, and were treated with 18F-FMISO. Then, their radioactivity after a 4 h incubation period under normoxic (21% O2) or hypoxic (1% O2) condition was measured. GST-P1 and MRP1 expression levels were measured by qRT-PCR. RESULTS: M2 macrophages exhibited a significantly higher uptake of 18F-FMISO than non-polarized (M0) macrophages, whereas M1 macrophages had a significantly lower uptake than M0 macrophages (M0: 1.05 ± 0.22, M1: 0.34 ± 0.02, M2: 4.17 ± 0.36 %dose/mg protein). The GST-P1 expression level in M1 macrophages was higher than that in M2 and M0 macrophages [GST-P1/β-actin normalized by M0: 9.0 ± 3.7 (M1), 1.2 ± 0.2 (M2)]. The MRP1 expression level in M1 macrophages was significantly higher than that in M2 and M0 macrophages [MRP1/β-actin normalized by M0 macrophages: 5.1 ± 2.1 (M1), 2.8 ± 1.0 (M2)]. CONCLUSIONS: 18F-FMISO accumulation in macrophages may depend on the polarization state in addition to hypoxic condition.

[18F]DPA-714 PET imaging shows immunomodulatory effect of intravenous administration of bone marrow stromal cells after transient focal ischemia.
Chengbo Tan, Songji Zhao, Kei Higashikawa, Zifeng Wang, Masahito Kawabori, Takeo Abumiya, Naoki Nakayama, Ken Kazumata, Naoyuki Ukon, Hironobu Yasui, Nagara Tamaki, Yuji Kuge, Hideo Shichinohe, Kiyohiro Houkin
EJNMMI research, 8, 1, 35, 35, 2018年05月02日, ［査読有り］, ［国際誌］
英語, BACKGROUND: The potential application of bone marrow stromal cell (BMSC) therapy in stroke has been anticipated due to its immunomodulatory effects. Recently, positron emission tomography (PET) with [18F]DPA-714, a translocator protein (TSPO) ligand, has become available for use as a neural inflammatory indicator. We aimed to evaluate the effects of BMSC administration after transient middle cerebral artery occlusion (MCAO) using [18F]DPA-714 PET. The BMSCs or vehicle were administered intravenously to rat MCAO models at 3 h after the insult. Neurological deficits, body weight, infarct volume, and histology were analyzed. [18F]DPA-714 PET was performed 3 and 10 days after MCAO. RESULTS: Rats had severe neurological deficits and body weight loss after MCAO. Cell administration ameliorated these effects as well as the infarct volume. Although weight loss occurred in the spleen and thymus, cell administration suppressed it. In both vehicle and BMSC groups, [18F]DPA-714 PET showed a high standardized uptake value (SUV) around the ischemic area 3 days after MCAO. Although SUV was increased further 10 days after MCAO in both groups, the increase was inhibited in the BMSC group, significantly. Histological analysis showed that an inflammatory reaction occurred in the lymphoid organs and brain after MCAO, which was suppressed in the BMSC group. CONCLUSIONS: The present results suggest that BMSC therapy could be effective in ischemic stroke due to modulation of systemic inflammatory responses. The [18F]DPA-714 PET/CT system can accurately demonstrate brain inflammation and evaluate the BMSC therapeutic effect in an imaging context. It has great potential for clinical application.

In vitro uptake and metabolism of [14C]acetate in rabbit atherosclerotic arteries: biological basis for atherosclerosis imaging with [11C]acetate
Kazuaki Yamasaki, Atsushi Yamashita, Yan Zhao, Yoichi Shimizu, Ryuichi Nishii, Keiichi Kawai, Nagara Tamaki, Songji Zhao, Yujiro Asada, Yuji Kuge
Nuclear Medicine and Biology, 56, 21, 25, Elsevier Inc., 2018年01月01日, ［査読有り］
英語, 研究論文（学術雑誌）

Measurement of Iodine-Derived Contamination in L-[¹¹C]Methionine Injection
Komatsu Yukiko, Tamaki Nagara, Kuge Yuji, Nishijima Ken-ichi, Oomagari Shigeo, Kanai Yasukazu, Naka Sadahiro, Higashikawa Kei, Ebita Yoko, Shiga Tohru, Hatazawa Jun
RADIOISOTOPES, 67, 3, 75, 83, 公益社団法人 日本アイソトープ協会, 2018年, ［査読有り］
英語,

L-［¹¹C］メチオニン注射液に混入する恐れのあるヨウ素由来不純物の測定法について検討した。試料には、L-［¹¹C］メチオニン注射液、及び気化したI₂を直接あるいはアスカライトカラムに通じた後にメチオニン合成を模した経路に導入・回収した試料を用いた。ICP-MS法、HPLC法、ジエチルパラフェニレンジアミン法により、全ヨウ素、ヨウ化物イオン、I₂を各々測定した。導入したI₂は、アスカライトカラムによりほとんどが捕集された。L-［¹¹C］メチオニン注射液中のヨウ素由来不純物は、主にヨウ化物イオンとして存在し、HPLC法により検出できた。HPLC法により、簡便かつ迅速にL-［¹¹C］メチオニン製剤中のヨウ素由来不純物を評価でき、製造工程管理に役立つと考えられた。

Anti PD-1 treatment increases [18F]FDG uptake by cancer cells in a mouse B16F10 melanoma model.
Tomita M, Yasui H, Higashikawa K, Nakajima K, Takakura H, Shiga T, Kuge Y, Ogawa M
EJNMMI Res, 8, 1, 82, Springer Science and Business Media LLC, 2018年, ［査読有り］
研究論文（学術雑誌）

Relationship between intelligence quotient (IQ) and cerebral metabolic rate of oxygen in patients with neurobehavioural disability after traumatic brain injury.　　　　　　　　　　　　　　　
Abiko K, Shiga T, Katoh C, Hirata K, Kuge Y, Kobayashi K, Ikeda S, Ikoma K
Brain Inj, 32, 11, 1367, 1372, 2018年, ［査読有り］

ホットセルに格納可能な小型RIガス貯留装置の開発
阿保 憲史, 野矢 洋一, 東川 桂, 安井 博宣, 久下 裕司
日本放射線安全管理学会誌, 16, 2, 85, 90, (一社)日本放射線安全管理学会, 2017年11月, ［査読有り］
日本語

In-111-DTPA-D-Phe(-1)-Asp(0)-D-Phe(1)-octreotide exhibits higher tumor accumulation and lower renal radioactivity than In-111-DTPA-D-Phe(1)-octreotide
Nobuhiro Oshima, Hiromichi Akizawa, Hirotake Kitaura, Hidekazu Kawashima, Songji Zhao, Yan Zhao, Ken-ichi Nishijima, Yoji Kitamura, Yasushi Arano, Yuji Kuge, Kazue Ohkura
NUCLEAR MEDICINE AND BIOLOGY, 54, 18, 26, 2017年11月, ［査読有り］
英語, 研究論文（学術雑誌）

FMISO accumulation in tumor is dependent on glutathione conjugation capacity in addition to hypoxic state
Yukiko Masaki, Yoichi Shimizu, Takeshi Yoshioka, Ken-ichi Nishijima, Songji Zhao, Kenichi Higashino, Yoshito Numata, Nagara Tamaki, Yuji Kuge
ANNALS OF NUCLEAR MEDICINE, 31, 8, 596, 604, 2017年10月, ［査読有り］
英語, 研究論文（学術雑誌）

F-18-Fluoromisonidazole positron emission tomography (FMISO-PET) may reflect hypoxia and cell proliferation activity in oral squamous cell carcinoma
Jun Sato, Yoshimasa Kitagawa, Shiro Watanabe, Takuya Asaka, Noritaka Ohga, Kenji Hirata, Shozo Okamoto, Tohru Shiga, Masanobu Shindoh, Yuji Kuge, Nagara Tamaki
ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY, 124, 3, 261, 270, 2017年09月, ［査読有り］
英語, 研究論文（学術雑誌）

Local relapse of nasopharyngeal cancer and Voxel-based analysis of FMISO uptake using PET with semiconductor detectors
Yukiko Nishikawa, Koichi Yasuda, Shozo Okamoto, Yoichi M. Ito, Rikiya Onimaru, Tohru Shiga, Kazuhiko Tsuchiya, Shiro Watanabe, Wataru Takeuchi, Yuji Kuge, Hao Peng, Nagara Tamaki, Hiroki Shirato
RADIATION ONCOLOGY, 12, 148, 2017年09月, ［査読有り］
英語, 研究論文（学術雑誌）

Changes in tumor oxygen state after sorafenib therapy evaluated by F-18-fluoromisonidazole hypoxia imaging of renal cell carcinoma xenografts
Wenwen Yu, Songji Zhao, Yan Zhao, Chowdhury Nusrat Fatema, Masahiro Murakami, Ken-Ichi Nishijima, Yoshimasa Kitagawa, Nagara Tamaki, Yuji Kuge
ONCOLOGY LETTERS, 14, 2, 2341, 2346, 2017年08月, ［査読有り］
英語, 研究論文（学術雑誌）

Immunoglobulin G (IgG)-Based Imaging Probe Accumulates in M1 Macrophage-Infiltrated Atherosclerotic Plaques Independent of IgG Target Molecule Expression
Yoichi Shimizu, Hiroko Hanzawa, Yan Zhao, Sagiri Fukura, Ken-ichi Nishijima, Takeshi Sakamoto, Songji Zhao, Nagara Tamaki, Mikako Ogawa, Yuji Kuge
MOLECULAR IMAGING AND BIOLOGY, 19, 4, 531, 539, 2017年08月, ［査読有り］
英語, 研究論文（学術雑誌）

Redesign of negatively charged In-111-DTPA-octreotide derivative to reduce renal radioactivity
Nobuhiro Oshima, Hiromichi Akizawa, Hidekazu Kawashima, Songji Zhao, Yan Zhao, Ken-ichi Nishijima, Yoji Kitamura, Yasushi Arano, Yuji Kuge, Kazue Ohkura
NUCLEAR MEDICINE AND BIOLOGY, 48, 16, 25, 2017年05月, ［査読有り］
英語, 研究論文（学術雑誌）

Hypoxic glucose metabolism in glioblastoma as a potential prognostic factor.
Takuya Toyonaga, Shigeru Yamaguchi, Kenji Hirata, Kentaro Kobayashi, Osamu Manabe, Shiro Watanabe, Shunsuke Terasaka, Hiroyuki Kobayashi, Naoya Hattori, Tohru Shiga, Yuji Kuge, Shinya Tanaka, Yoichi M Ito, Nagara Tamaki
European journal of nuclear medicine and molecular imaging, 44, 4, 611, 619, 2017年04月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, PURPOSE: Metabolic activity and hypoxia are both important factors characterizing tumor aggressiveness. Here, we used F-18 fluoromisonidazole (FMISO) and F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) to define metabolically active hypoxic volume, and investigate its clinical significance in relation to progression free survival (PFS) and overall survival (OS) in glioblastoma patients. EXPERIMENTAL DESIGN: Glioblastoma patients (n = 32) underwent FMISO PET, FDG PET, and magnetic resonance imaging (MRI) before surgical intervention. FDG and FMISO PET images were coregistered with gadolinium-enhanced T1-weighted MR images. Volume of interest (VOI) of gross tumor volume (GTV) was manually created to enclose the entire gadolinium-positive areas. The FMISO tumor-to-normal region ratio (TNR) and FDG TNR were calculated in a voxel-by-voxel manner. For calculating TNR, standardized uptake value (SUV) was divided by averaged SUV of normal references. Contralateral frontal and parietal cortices were used as the reference region for FDG, whereas the cerebellar cortex was used as the reference region for FMISO. FDG-positive was defined as the FDG TNR ≥1.0, and FMISO-positive was defined as FMISO TNR ≥1.3. Hypoxia volume (HV) was defined as the volume of FMISO-positive and metabolic tumor volume in hypoxia (hMTV) was the volume of FMISO/FDG double-positive. The total lesion glycolysis in hypoxia (hTLG) was hMTV × FDG SUVmean. The extent of resection (EOR) involving cytoreduction surgery was volumetric change based on planimetry methods using MRI. These factors were tested for correlation with patient prognosis. RESULTS: All tumor lesions were FMISO-positive and FDG-positive. Univariate analysis indicated that hMTV, hTLG, and EOR were significantly correlated with PFS (p = 0.007, p = 0.04, and p = 0.01, respectively) and that hMTV, hTLG, and EOR were also significantly correlated with OS (p = 0.0028, p = 0.037, and p = 0.014, respectively). In contrast, none of FDG TNR, FMISO TNR, GTV, HV, patients' age, or Karnofsky performance scale (KPS) was significantly correlated with PSF or OS. The hMTV and hTLG were found to be independent factors affecting PFS and OS on multivariate analysis. CONCLUSIONS: We introduced hMTV and hTLG using FDG and FMISO PET to define metabolically active hypoxic volume. Univariate and multivariate analyses demonstrated that both hMTV and hTLG are significant predictors for PFS and OS in glioblastoma patients.

Altered glucose metabolism and hypoxic response in alloxan-induced diabetic atherosclerosis in rabbits
Yunosuke Matsuura, Atsushi Yamashita, Yan Zhao, Takashi Iwakiri, Kazuaki Yamasaki, Chihiro Sugita, Chihiro Koshimoto, Kazuo Kitamura, Keiichi Kawai, Nagara Tamaki, Songji Zhao, Yuji Kuge, Yujiro Asada
PLOS ONE, 12, 4, e0175976, 2017年04月, ［査読有り］
英語, 研究論文（学術雑誌）

I-123 iomazenil single photon emission computed tomography for detecting loss of neuronal integrity in patients with traumatic brain injury
Kagari Abiko, Katsunori Ikoma, Tohru Shiga, Chietsugu Katoh, Kenji Hirata, Yuji Kuge, Kentaro Kobayashi, Nagara Tamaki
EJNMMI RESEARCH, 7, 1, 28, 2017年03月, ［査読有り］
英語, 研究論文（学術雑誌）

Dynamic PET evaluation of elevated FLT level after sorafenib treatment in mice bearing human renal cell carcinoma xenograft
Naoyuki Ukon, Songji Zhao, Wenwen Yu, Yoichi Shimizu, Ken-ichi Nishijima, Naoki Kubo, Yoshimasa Kitagawa, Nagara Tamaki, Kei Higashikawa, Hironobu Yasui, Yuji Kuge
EJNMMI RESEARCH, 6, 1, 90, 2016年12月, ［査読有り］
英語, 研究論文（学術雑誌）

The reoxygenation of hypoxia and the reduction of glucose metabolism in head and neck cancer by fractionated radiotherapy with intensity-modulated radiation therapy
Shozo Okamoto, Tohru Shiga, Koichi Yasuda, Shiro Watanabe, Kenji Hirata, Ken-ichi Nishijima, Keiichi Magota, Katsuhiko Kasai, Rikiya Onimaru, Kazuhiko Tuchiya, Yuji Kuge, Hiroki Shirato, Nagara Tamaki
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, 43, 12, 2147, 2154, 2016年11月, ［査読有り］
英語, 研究論文（学術雑誌）

Imaging Mass Spectrometry Revealed the Accumulation Characteristics of the 2-Nitroimidazole-Based Agent "Pimonidazole" in Hypoxia
Yukiko Masaki, Yoichi Shimizu, Takeshi Yoshioka, Fei Feng, Songji Zhao, Kenichi Higashino, Yoshito Numata, Yuji Kuge
PLOS ONE, 11, 8, e0161639, 2016年08月, ［査読有り］
英語, 研究論文（学術雑誌）

The Thymidine Phosphorylase Imaging Agent I-123-IIMU Predicts the Efficacy of Capecitabine
Nobuya Kobashi, Hiroki Matsumoto, Songji Zhao, Shunsuke Meike, Yuki Okumura, Tsutomu Abe, Hiromichi Akizawa, Kazue Ohkura, Ken-ichi Nishijima, Nagara Tamaki, Yuji Kuge
JOURNAL OF NUCLEAR MEDICINE, 57, 8, 1276, 1281, 2016年08月, ［査読有り］
英語, 研究論文（学術雑誌）

Characterization of the role of sphingomyelin synthase 2 in glucose metabolism in whole-body and peripheral tissues in mice
Masayuki Sugimoto, Yoichi Shimizu, Songji Zhao, Naoyuki Ukon, Ken-ichi Nishijima, Masato Wakabayashi, Takeshi Yoshioka, Kenichi Higashino, Yoshito Numata, Tomohiko Okuda, Nagara Tamaki, Hisatoshi Hanamatsu, Yasuyuki Igarashi, Yuji Kuge
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS, 1861, 8, 688, 702, 2016年08月, ［査読有り］
英語, 研究論文（学術雑誌）

Continuous-Flow Synthesis of N-Succinimidyl 4-[F-18]fluorobenzoate Using a Single Microfluidic Chip
Hiroyuki Kimura, Kenji Tomatsu, Hidekazu Saiki, Kenji Arimitsu, Masahiro Ono, Hidekazu Kawashima, Ren Iwata, Hiroaki Nakanishi, Eiichi Ozeki, Yuji Kuge, Hideo Saji
PLOS ONE, 11, 7, e0159303, 2016年07月, ［査読有り］
英語, 研究論文（学術雑誌）

(18)F-fluoromisonidazole positron emission tomography can predict pathological necrosis of brain tumors.
Takuya Toyonaga, Kenji Hirata, Shigeru Yamaguchi, Kanako C Hatanaka, Sayaka Yuzawa, Osamu Manabe, Kentaro Kobayashi, Shiro Watanabe, Tohru Shiga, Shunsuke Terasaka, Hiroyuki Kobayashi, Yuji Kuge, Nagara Tamaki
European journal of nuclear medicine and molecular imaging, 43, 8, 1469, 76, 2016年07月, ［査読有り］, ［国際誌］
英語, PURPOSE: Tumor necrosis is one of the indicators of tumor aggressiveness. (18)F-fluoromisonidazole (FMISO) is the most widely used positron emission tomography (PET) tracer to evaluate severe hypoxia in vivo. Because severe hypoxia causes necrosis, we hypothesized that intratumoral necrosis can be detected by FMISO PET in brain tumors regardless of their histopathology. We applied FMISO PET to various types of brain tumors before tumor resection and evaluated the correlation between histopathological necrosis and FMISO uptake. METHODS: This study included 59 brain tumor patients who underwent FMISO PET/computed tomography before any treatments. According to the pathological diagnosis, the brain tumors were divided into three groups: astrocytomas (group 1), neuroepithelial tumors except for astrocytomas (group 2), and others (group 3). Two experienced neuropathologists evaluated the presence of necrosis in consensus. FMISO uptake in the tumor was evaluated visually and semi-quantitatively using the tumor-to-normal cerebellum ratio (TNR). RESULTS: In visual analyses, 26/27 cases in the FMISO-positive group presented with necrosis, whereas 28/32 cases in the FMISO-negative group did not show necrosis. Mean TNRs with and without necrosis were 3.49 ± 0.97 and 1.43 ± 0.42 (p < 0.00001) in group 1, 2.91 ± 0.83 and 1.44 ± 0.20 (p < 0.005) in group 2, and 2.63 ± 1.16 and 1.35 ± 0.23 (p < 0.05) in group 3, respectively. Using a cut-off value of TNR = 1.67, which was calculated by normal reference regions of interest, we could predict necrosis with sensitivity, specificity, and accuracy of 96.7, 93.1, and 94.9 %, respectively. CONCLUSIONS: FMISO uptake within the lesion indicated the presence of histological micro-necrosis. When we used a TNR of 1.67 as the cut-off value, intratumoral micro-necrosis was sufficiently predictable. Because the presence of necrosis implies a poor prognosis, our results suggest that FMISO PET could provide important information for treatment decisions or surgical strategies of any type of brain tumor.

Imaging Mass Spectrometry Reveals Acyl-Chain- and Region-Specific Sphingolipid Metabolism in the Kidneys of Sphingomyelin Synthase 2-Deficient Mice
Masayuki Sugimoto, Masato Wakabayashi, Yoichi Shimizu, Takeshi Yoshioka, Kenichi Higashino, Yoshito Numata, Tomohiko Okuda, Songji Zhao, Shota Sakai, Yasuyuki Igarashi, Yuji Kuge
PLOS ONE, 11, 3, e0152191, 2016年03月, ［査読有り］
英語, 研究論文（学術雑誌）

Optimization of helical acquisition parameters to preserve uniformity of mouse whole body using multipinhole collimator in single-photon emission computed tomography
Naoyuki Ukon, Naoki Kubo, Masayori Ishikawa, Songji Zhao, Nagara Tamaki, Yuji Kuge
Results in Physics, 6, 659, 663, 2016年, ［査読有り］
英語, 研究論文（学術雑誌）

Histological analyses by matrix-assisted laser desorption/ionization-imaging mass spectrometry reveal differential localization of sphingomyelin molecular species regulated by particular ceramide synthase in mouse brains.
Masayuki Sugimoto, Yoichi Shimizu, Takeshi Yoshioka, Masato Wakabayashi, Yukari Tanaka, Kenichi Higashino, Yoshito Numata, Shota Sakai, Akio Kihara, Yasuyuki Igarashi, Yuji Kuge
Biochimica et biophysica acta, 1851, 12, 1554, 65, 2015年12月, ［査読有り］, ［国際誌］
英語, Sphingomyelin (SM) is synthesized by SM synthase (SMS) from ceramide (Cer). SM regulates signaling pathways and maintains organ structure. SM comprises a sphingoid base and differing lengths of acyl-chains, but the importance of its various forms and regulatory synthases is not known. It has been reported that Cer synthase (CerS) has restricted substrate specificity, whereas SMS has no specificity for different lengths of acyl-chains. We hypothesized that the distribution of each SM molecular species was regulated by expression of the CerS family. Thus, we compared the distribution of SM species and CerS mRNA expression using molecular imaging. Spatial distribution of each SM molecular species was investigated using ultra-high-resolution imaging mass spectrometry (IMS). IMS revealed that distribution of SM molecular species varied according to the lengths of acyl-chains found in each brain section. Furthermore, a combination study using in situ hybridization and IMS revealed the spatial expression of CerS1 to be associated with the localization of SM (d18:1/18:0) in cell body-rich gray matter, and CerS2 to be associated with SM (d18:1/24:1) in myelin-rich white matter. Our study is the first comparison of spatial distribution between SM molecular species and CerS isoforms, and revealed their distinct association in the brain. These observations were demonstrated by suppression of CerS2 using siRNA in HepG2 cells; that is, siRNA for CerS2 specifically decreased C22 very long-chain fatty acid (VLCFA)- and C24 VLCFA-containing SMs. Thus, histological analyses of SM species by IMS could be a useful approach to consider their molecular function and regulative mechanism.

The accumulation mechanism of the hypoxia imaging probe "FMISO" by imaging mass spectrometry: possible involvement of low-molecular metabolites
Yukiko Masaki, Yoichi Shimizu, Takeshi Yoshioka, Yukari Tanaka, Ken-ichi Nishijima, Songji Zhao, Kenichi Higashino, Shingo Sakamoto, Yoshito Numata, Yoshitaka Yamaguchi, Nagara Tamaki, Yuji Kuge
SCIENTIFIC REPORTS, 5, 16802, 2015年11月, ［査読有り］
英語, 研究論文（学術雑誌）

Combined Plasma and Tissue Proteomic Study of Atherogenic Model Mouse: Approach To Elucidate Molecular Determinants in Atherosclerosis Development
Hiroko Hanzawa, Takeshi Sakamoto, Akihito Kaneko, Naomi Manri, Yan Zhao, Songji Zhao, Nagara Tamaki, Yuji Kuge
JOURNAL OF PROTEOME RESEARCH, 14, 10, 4257, 4269, 2015年10月, ［査読有り］
英語, 研究論文（学術雑誌）

Application of Microreactor to the Preparation of C-11-Labeled Compounds via O-[C-11]Methylation with [C-11]CH3I: Rapid Synthesis of [C-11]Raclopride
Hidekazu Kawashima, Hiroyuki Kimura, Yuta Nakaya, Kenji Tomatsu, Kenji Arimitsu, Hiroaki Nakanishi, Eiichi Ozeki, Yuji Kuge, Hideo Saji
CHEMICAL & PHARMACEUTICAL BULLETIN, 63, 9, 737, 740, 2015年09月, ［査読有り］
英語, 研究論文（学術雑誌）

Relationship between biodistribution of a novel thymidine phosphorylase (TP) imaging probe and TP expression levels in normal mice
Songji Zhao, Hua Li, Ken-ichi Nishijima, Yan Zhao, Hiromichi Akizawa, Yoichi Shimizu, Kazue Ohkura, Nagara Tamaki, Yuji Kuge
ANNALS OF NUCLEAR MEDICINE, 29, 7, 582, 587, 2015年08月, ［査読有り］
英語, 研究論文（学術雑誌）

Prognostic value of volume-based measurements on (11)C-methionine PET in glioma patients.
Kentaro Kobayashi, Kenji Hirata, Shigeru Yamaguchi, Osamu Manabe, Shunsuke Terasaka, Hiroyuki Kobayashi, Tohru Shiga, Naoya Hattori, Shinya Tanaka, Yuji Kuge, Nagara Tamaki
European journal of nuclear medicine and molecular imaging, 42, 7, 1071, 80, 2015年06月, ［査読有り］, ［国際誌］
英語, PURPOSE: (11)C-methionine (MET) PET is an established diagnostic tool for glioma. Studies have suggested that MET uptake intensity in the tumor is a useful index for predicting patient outcome. Because MET uptake is known to reflect tumor expansion more accurately than MRI, we aimed to elucidate the association between volume-based tumor measurements and patient prognosis. METHODS: The study population comprised 52 patients with newly diagnosed glioma who underwent PET scanning 20 min after injection of 370 MBq MET. The tumor was contoured using a threshold of 1.3 times the activity of the contralateral normal cortex. Metabolic tumor volume (MTV) was defined as the total volume within the boundary. Total lesion methionine uptake (TLMU) was defined as MTV times the mean standardized uptake value (SUVmean) within the boundary. The tumor-to-normal ratio (TNR), calculated as the maximum standardized uptake value (SUVmax) divided by the contralateral reference value, was also recorded. All patients underwent surgery (biopsy or tumor resection) targeting the tissue with high MET uptake. The Kaplan-Meier method was used to estimate the predictive value of each measurement. RESULTS: Grade II tumor was diagnosed in 12 patients (3 diffuse astrocytoma, 2 oligodendroglioma, and 7 oligoastrocytoma), grade III in 18 patients (8 anaplastic astrocytoma, 6 anaplastic oligodendroglioma, and 4 anaplastic oligoastrocytoma), and grade IV in 22 patients (all glioblastoma). TNR, MTV and TLMU were 3.1 ± 1.2, 51.6 ± 49.9 ml and 147.7 ± 153.3 ml, respectively. None of the three measurements was able to categorize the glioma patients in terms of survival when all patients were analyzed. However, when only patients with astrocytic tumor (N = 33) were analyzed (i.e., when those with oligodendroglial components were excluded), MTV and TLMU successfully predicted patient outcome with higher values associated with a poorer prognosis (P < 0.05 and P < 0.01, respectively), while the predictive ability of TNR did not reach statistical significance (P = NS). CONCLUSION: MTV and TLMU may be useful for predicting outcome in patients with astrocytic tumor.

Oligodendroglial component complicates the prediction of tumour grading with metabolic imaging.
Osamu Manabe, Naoya Hattori, Shigeru Yamaguchi, Kenji Hirata, Kentaro Kobayashi, Shunsuke Terasaka, Hiroyuki Kobayashi, Hiroaki Motegi, Tohru Shiga, Keiichi Magota, Noriko Oyama-Manabe, Ken-ichi Nishijima, Yuji Kuge, Nagara Tamaki
European journal of nuclear medicine and molecular imaging, 42, 6, 896, 904, 2015年05月, ［査読有り］, ［国際誌］
英語, PURPOSE: Previous radiological investigations have generally shown the superiority of metabolic imaging in distinguishing high-grade from low-grade glioma, but the presence of an oligodendroglial component may affect the diagnostic accuracy. We investigated the diagnostic accuracy of PET imaging using (11)C-methionine (MET) and (18)F-fluorodeoxyglucose (FDG) in distinguishing high-grade from low-grade glioma, in correlation with the oligodendroglial component. METHODS: The study population comprised adult patients who underwent preoperative PET imaging using both MET and FDG within 1 week and successful excision of the tumour tissue, which confirmed WHO grade II-IV glioma. We examined the tumour metabolic activity in terms of lesion-to-normal uptake ratios (L/N ratio) in both MET PET and FDG PET images. We assessed the correlation between the imaging results and the histological findings to determine the diagnostic accuracy of receiver operating characteristics (ROC) analysis in detecting high-grade tumours. RESULTS: We studied 46 patients with glioma (13 low-grade and 33 high-grade), including 26 with an oligodendroglial components. The L/N ratios of the PET images showed significantly higher metabolic activities in high-grade gliomas than in low-grade gliomas for both MET (4.29 ± 1.22 and 2.36 ± 0.72, respectively; p < 0.0001) and FDG (1.72 ± 0.91 and 0.77 ± 0.26, respectively; p = 0.0007) images, although significant overlaps in L/N ratio were observed between high-grade and low-grade gliomas. Excluding the 26 patents with an oligodendroglial component improved the separation for both MET (4.62 ± 1.14 vs. 2.16 ± 0.63; p < 0.001) and FDG (1.76 ± 0.87 vs. 0.71 ± 0.14; p < 0.05) images. The ROC analyses demonstrated the clinical utility of the metabolic radiotracers in distinguishing high-grade from low-grade gliomas, showing similar AUC values for MET (0.91) and FDG (0.92). Excluding the 26 patents with an oligodendroglial component also further improved the diagnostic accuracy for both MET (AUC 0.98), and FDG (AUC 1.00) images. The metabolic radiotracers were significantly correlated with the MIB-1 labelling index (R = 0.52, p < 0.05 for MET; R = 0.52, p < 0.05, for FDG) only in gliomas without an oligodendroglial component. CONCLUSION: For better characterization of gliomas and for risk assessment, the results of metabolic PET imaging should be revised after obtaining the pathological report, because oligodendroglial differentiation may positively influence the substrate metabolism and thus complicated the preoperative evaluation.

Differentiation of malignant tumours from granulomas by using dynamic [18F]-fluoro-L-α-methyltyrosine positron emission tomography
Yamaguchi A, Hanaoka H, Fujisawa Y, Zhao S, Suzue K, Morita A, Tominaga H, Higuchi T, Hisaeda H, Tsushima Y, Kuge Y, Iida Y
EJNMMI Res, 5, 29, 2015年04月, ［査読有り］
英語, 研究論文（学術雑誌）

Radiolabeled BMIPP for Imaging Hepatic Fatty Acid Metabolism: Evaluation of Hepatic Distribution and Metabolism in Mice at Various Metabolic Statuses Induced by Fasting in Comparison with Palmitic Acid
Kazuaki Yamasaki, Songji Zhao, Mie Nishimura, Yan Zhao, Wenwen Yu, Yoichi Shimizu, Ken-ichi Nishijima, Nagara Tamaki, Hiroshi Takeda, Yuji Kuge
MOLECULAR IMAGING, 14, 0, 1, 11, 2015年04月, ［査読有り］
英語, 研究論文（学術雑誌）

Regulatory Effect of Interleukin-4 in the Innate Inflammatory Response to Rhodococcus aurantiacus Infection in Mice
Yimin, Masashi Kohanawa, Songji Zhao, Minqi Li, Yuji Kuge, Nagara Tamaki, Masahiko Watanabe
JOURNAL OF INTERFERON AND CYTOKINE RESEARCH, 35, 3, 222, 231, 2015年03月, ［査読有り］
英語, 研究論文（学術雑誌）

Irbesartan attenuates atherosclerosis in Watanabe Heritable Hyperlipidemic rabbits: Noninvasive imaging of inflammation by 18F-FDG PET
Zhao Y, Fukao K, Zhao S, Watanabe A, Hamada T, Yamasaki K, Shimizu Y, Kubo N, Ukon N, Nakano T, Tamaki N, Kuge Y
Mol Imaging, 14, 0, 1, 8, 2015年, ［査読有り］

Prone-position acquisition of myocardial (123)I-metaiodobenzylguanidine (MIBG) SPECT reveals regional uptake similar to that found using (11)C-hydroxyephedrine PET/CT.
Keiichiro Yoshinaga, Yuuki Tomiyama, Osamu Manabe, Katsuhiko Kasai, Chietsugu Katoh, Kenichi Magota, Eriko Suzuki, Ken-Ichi Nishijima, Yuji Kuge, Yoichi M Ito, Nagara Tamaki
Annals of nuclear medicine, 28, 8, 761, 9, 2014年10月, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）, OBJECTIVES: (123)I-metaiodobenzylguanidine (MIBG) has been used to estimate cardiac sympathetic nervous innervation. Heterogeneous MIBG distribution is mainly associated with high physiological MIBG uptakes in the liver. We postulate that prone position acquisition might be especially effective for MIBG, providing for separation from high liver uptake similar to that provided by perfusion single-photon emission computed tomography (SPECT). We investigated whether prone-position acquisition improved MIBG image quality by comparing our results to those acquired using supine MIBG and high-quality (11)C-hydroxyephedrine (HED) positron emission tomography/computed tomography PET/CT. METHODS: Ten male volunteers (body mass index (BMI) 22.7 ± 3.4) underwent prone and supine MIBG and HED PET. Relative regional tracer uptake was estimated in early MIBG and HED. Acquired images were divided into 17 segments and were grouped into 4 regions: anterior, inferior, septum, and lateral. For each patient, the inferior/anterior ratio was calculated. RESULTS: The quality of images acquired using prone MIBG was better than that using supine MIBG (p < 0.05). Inferior and septum relative MIBG uptake was reduced in comparison with anterior or lateral MIBG uptake in the supine position (inferior vs. anterior: 69.0 ± 5.6 vs. 82.3 ± 4.6 %, p < 0.01; septum vs. lateral: 66.2 ± 5.1 vs. 81.9 ± 5.4 %, p < 0.01). Prone MIBG showed a significantly higher inferior/anterior uptake ratio in comparison with supine MIBG (n = 24, seg: 92.2 ± 7.2 vs. 83.6 ± 5.7 %, p < 0.05). However, intergroup differences in uptake ratio were demonstrated among prone and supine MIBG and HED. HED PET/CT still showed a higher uptake ratio in comparison with prone MIBG SPECT (103.9 ± 8.0 vs. 92.2 ± 7.2 %, p < 0.05). CONCLUSION: Even in normal male subjects, standard supine MIBG imaging showed reduced inferior and septum uptake. Uptake with prone MIBG imaging showed a significant improvement over that with supine imaging and was closer to uptake for HED PET/CT. This improvement may be the result of preventing intense uptake by the liver. Prone data acquisition may be a viable alternative in evaluating regional abnormalities using MIBG SPECT in men.

A Simple and Rapid Method for Standard Preparation of Gas Phase Extract of Cigarette Smoke
Tsunehito Higashi, Yosuke Mai, Yoichi Noya, Takahiro Horinouchi, Koji Terada, Akimasa Hoshi, Prabha Nepal, Takuya Harada, Mika Horiguchi, Chizuru Hatate, Yuji Kuge, Soichi Miwa
PLOS ONE, 9, 9, e107856, 2014年09月, ［査読有り］
英語, 研究論文（学術雑誌）

Dual tracer evaluation of dynamic changes in intratumoral hypoxic and proliferative states after radiotherapy of human head and neck cancer xenografts using radiolabeled FMISO and FLT
Chowdhury Nusrat Fatema, Songji Zhao, Yan Zhao, Wenwen Yu, Ken-ichi Nishijima, Koichi Yasuda, Yoshimasa Kitagawa, Nagara Tamaki, Yuji Kuge
BMC CANCER, 14, 1, 692, 2014年09月, ［査読有り］
英語, 研究論文（学術雑誌）

Evaluation of delineation of image details in semiconductor PET utilizing the normalized mutual information technique
Naoki Kubo, Kenji Hirata, Kazuki Matsuzaki, Yuichi Morimoto, Wataru Takeuchi, Naoya Hattori, Tohru Shiga, Yuji Kuge, Nagara Tamaki
NUCLEAR MEDICINE COMMUNICATIONS, 35, 6, 677, 682, 2014年06月, ［査読有り］
英語, 研究論文（学術雑誌）

Electrocardiographically gated ¹¹C-hydroxyephedrine PET for the simultaneous assessment of cardiac sympathetic and contractile functions.
Keiichi Magota, Naoya Hattori, Osamu Manabe, Masanao Naya, Noriko Oyama-Manabe, Tohru Shiga, Yuji Kuge, Shiro Yamada, Mamoru Sakakibara, Keiichiro Yoshinaga, Nagara Tamaki
Annals of nuclear medicine, 28, 3, 187, 95, 2014年04月, ［査読有り］, ［国内誌］
英語, OBJECTIVE: Application of the electrocardiographically (ECG) gated positron emission tomography (PET) technique with (11)C-hydroxyephedrine (HED) would allow the simultaneous assessment of cardiac sympathetic and contractile functions. However, there are uncertainties regarding the diagnostic accuracy of left ventricular (LV) volume measurements using ECG-gated HED-PET. The purpose of this study was to clarify the minimal requirement of count statistics to measure LV volumes with ECG-gated HED-PET and to investigate the reliability of the measurements. METHODS: Five healthy volunteers and 11 patients with heart failure underwent a 40-min list-mode PET scan after an injection of HED (197 ± 35 MBq). The list-mode data were histogrammed into multiple sets of acquisition periods at 0.5, 1.0, 2.0, 4.0, 6.0, 8.0, 12.0 Mcount/bin and reconstructed into corresponding gated images using an iterative algorithm. The LV end-diastolic volume (LVEDV), the LV end-systolic volume (LVESV), and the LV ejection fraction (LVEF) were calculated in each acquisition period. These values were compared with those obtained by cardiac magnetic resonance imaging (MRI). Possible effects of HED retention on the accuracy of the volume measurements were investigated. RESULTS: Collecting less than 4.0 Mcount/bin resulted in noisy cardiac images. The lower counts resulted in underestimation in the volume measurements. Reasonably accurate volume measurements required equal to or greater than 6.0 Mcount/bin. This corresponded to 7.0 ± 1.9 min (range, 4.0-10.3 min) for the acquisition period. Volumetric results using the 6.0 Mcount/bin data highly correlated with cardiac MRI (LVEDV: r = 0.85, p < 0.0001; LVESV: r = 0.89, p < 0.0001; LVEF: r = 0.77, p < 0.01). The HED retention did not affect the volumetric results compared to the MRI volumetry. CONCLUSIONS: The volumetric accuracy with ECG-gated HED-PET was affected by the count statistics rather than the HED retention. LV volume measurements were feasible with 10-min acquisition period for most of the patients. This technique allows the simultaneous assessment of cardiac sympathetic and contractile functions without the need for an additional injection or scanning time, thus reducing overall costs for diagnostic imaging.

Suppressive Effects of Irbesartan on Inflammation and Apoptosis in Atherosclerotic Plaques of apoE(-/-) Mice: Molecular Imaging with C-14-FDG and Tc-99m-Annexin A5
Yan Zhao, Ayahisa Watanabe, Songji Zhao, Tatsuo Kobayashi, Keita Fukao, Yoshikazu Tanaka, Toru Nakano, Tetsuya Yoshida, Hiroshi Takemoto, Nagara Tamaki, Yuji Kuge
PLOS ONE, 9, 2, e89338, 2014年02月, ［査読有り］
英語, 研究論文（学術雑誌）

Design, synthesis and biological evaluation of negatively charged In-111-DTPA-octreotide derivatives
Nobuhiro Oshima, Hiromichi Akizawa, Songji Zhao, Yan Zhao, Ken-ichi Nishijima, Yoji Kitamura, Yasushi Arano, Yuji Kuge, Kazue Ohkura
BIOORGANIC & MEDICINAL CHEMISTRY, 22, 4, 1377, 1382, 2014年02月, ［査読有り］
英語, 研究論文（学術雑誌）

Advantage of FMISO-PET over FDG-PET for predicting histological response to preoperative chemotherapy in patients with oral squamous cell carcinoma
Jun Sato, Yoshimasa Kitagawa, Yutaka Yamazaki, Hironobu Hata, Takuya Asaka, Masaaki Miyakoshi, Shozo Okamoto, Tohru Shiga, Masanobu Shindoh, Yuji Kuge, Nagara Tamaki
European Journal of Nuclear Medicine and Molecular Imaging, 41, 11, 2031, 2041, springer berlin, 2014年, ［査読有り］
英語, 研究論文（学術雑誌）

Increased Metabolite Levels of Glycolysis and Pentose Phosphate Pathway in Rabbit Atherosclerotic Arteries and Hypoxic Macrophage
Atsushi Yamashita, Yan Zhao, Yunosuke Matsuura, Kazuaki Yamasaki, Sayaka Moriguchi-Goto, Chihiro Sugita, Takashi Iwakiri, Nozomi Okuyama, Chihiro Koshimoto, Keiichi Kawai, Nagara Tamaki, Songji Zhao, Yuji Kuge, Yujiro Asada
PLOS ONE, 9, 1, e86426, 2014年01月, ［査読有り］
英語, 研究論文（学術雑誌）

Identification of stable cytotoxic factors in the gas phase extract of cigarette smoke and pharmacological characterization of their cytotoxicity
Yoichi Noya, Koh-ichi Seki, Hiroshi Asano, Yosuke Mai, Takahiro Horinouchi, Tsunehito Higashi, Koji Terada, Chizuru Hatate, Akimasa Hoshi, Prabha Nepal, Mika Horiguchi, Yuji Kuge, Soichi Miwa
Toxicology, 314, 1, 1, 10, Elsevier Ireland Ltd, 2013年12月06日, ［査読有り］
英語, 研究論文（学術雑誌）

Assessment of early changes in H-3-fluorothymidine uptake after treatment with gefitinib in human tumor xenograft in comparison with Ki-67 and phospho-EGFR expression
Songji Zhao, Yuji Kuge, Yan Zhao, Satoshi Takeuchi, Kenji Hirata, Toshiki Takei, Tohru Shiga, Hirotoshi Dosaka-Akita, Nagara Tamaki
BMC CANCER, 13, 1, 525, 2013年11月, ［査読有り］
英語, 研究論文（学術雑誌）

I-123-Iomazenil Single Photon Emission Computed Tomography Visualizes Recovery of Neuronal Integrity by Bone Marrow Stromal Cell Therapy in Rat Infarct Brain
Hisayasu Saito, Keiichi Magota, Songji Zhao, Naoki Kubo, Yuji Kuge, Hideo Shichinohe, Kiyohiro Houkin, Nagara Tamaki, Satoshi Kuroda
STROKE, 44, 10, 2869, 2874, 2013年10月, ［査読有り］
英語, 研究論文（学術雑誌）

Contribution of Toll-Like Receptor 2 to the Innate Response against Staphylococcus aureus Infection in Mice
Yimin, Masashi Kohanawa, Songji Zhao, Michitaka Ozaki, Sanae Haga, Guangxian Nan, Yuji Kuge, Nagara Tamaki
PLoS ONE, 8, 9, e74287, 2013年09月13日, ［査読有り］
英語, 研究論文（学術雑誌）

Increased intratumoral fluorothymidine uptake levels following multikinase inhibitor sorafenib treatment in a human renal cell carcinoma xenograft model
Masahiro Murakami, Songji Zhao, Yan Zhao, Wenwen Yu, Chowdhury Nusrat Fatema, Ken-Ichi Nishijima, Masahiro Yamasaki, Mitsuyoshi Takiguchi, Nagara Tamaki, Yuji Kuge
Oncology Letters, 6, 3, 667, 672, 2013年09月, ［査読有り］
英語, 研究論文（学術雑誌）

Elevated F-18-FDG Levels in Blood and Organs After Angiotensin II Receptor Blocker Administration: Experiment in Mice Administered Telmisartan
Yan Zhao, Songji Zhao, Yuji Kuge, Nagara Tamaki
JOURNAL OF NUCLEAR MEDICINE, 54, 8, 1384, 1388, 2013年08月, ［査読有り］
英語, 研究論文（学術雑誌）

Radiation-induced nitric oxide mitigates tumor hypoxia and radioresistance in a murine SCCVII tumor model
Masaki Nagane, Hironobu Yasui, Tohru Yamamori, Songji Zhao, Yuji Kuge, Nagara Tamaki, Hiromi Kameya, Hideo Nakamura, Hirotada Fujii, Osamu Inanami
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 437, 3, 420, 425, 2013年08月, ［査読有り］
英語, 研究論文（学術雑誌）

18F-Fluoromisonidazole PET Uptake Is Correlated with Hypoxia-Inducible Factor-1α Expression in Oral Squamous Cell Carcinoma.
Sato J, Kitagawa Y, Yamazaki Y, Hata H, Okamoto S, Shiga T, Shindoh M, Kuge Y, Tamaki N
J Nucl Med., 54, 7, 1060, 1065, 2013年07月, ［査読有り］
英語, 研究論文（学術雑誌）

Attenuation of Apoptosis by Telmisartan in Atherosclerotic Plaques of Apolipoprotein E-/- Mice: Evaluation Using Technetium 99m-Annexin A5
Yan Zhao, Songji Zhao, Yuji Kuge, H. William Strauss, Francis G. Blankenberg, Nagara Tamaki
MOLECULAR IMAGING, 12, 5, 300, 309, 2013年07月, ［査読有り］
英語, 研究論文（学術雑誌）

Synthesis and evaluation of 11C-labeled naphthalene derivative as a novel non-peptidergic probe for the β-secretase (BACE1) imaging in Alzheimer's disease brain.
Kawai T, Kawashima H, Kuge Y, Saji H
Nucl Med Biol., 40, 5, 705, 709, 2013年07月, ［査読有り］
英語, 研究論文（学術雑誌）

Monitoring tumor proliferative response to radiotherapy using F-18-fluorothymidine in human head and neck cancer xenograft in comparison with Ki-67
Chowdhury Nusrat Fatema, Songji Zhao, Yan Zhao, Masahiro Murakami, Wenwen Yu, Ken-ichi Nishijima, Nagara Tamaki, Yoshimasa Kitagawa, Yuji Kuge
ANNALS OF NUCLEAR MEDICINE, 27, 4, 355, 362, 2013年05月, ［査読有り］
英語, 研究論文（学術雑誌）

Timing and cell dose determine therapeutic effects of bone marrow stromal cell transplantation in rat model of cerebral infarct
Masahito Kawabori, Satoshi Kuroda, Masaki Ito, Hideo Shichinohe, Kiyohiro Houkin, Yuji Kuge, Nagara Tamaki
NEUROPATHOLOGY, 33, 2, 140, 148, 2013年04月, ［査読有り］
英語, 研究論文（学術雑誌）

Biological characteristics of intratumoral [F-18]-fluoromisonidazole distributionin a rodent model of glioma
Toshiyuki Hatano, Songji Zhao, Yan Zhao, Ken-Ichi Nishijima, Norihito Kuno, Hiroko Hanzawa, Takeshi Sakamoto, Nagara Tamaki, Yuji Kuge
International Journal of Oncology, 42, 3, 823, 830, 2013年03月, ［査読有り］
英語, 研究論文（学術雑誌）

High Reproducibility of Tumor Hypoxia Evaluated by F-18-Fluoromisonidazole PET for Head and Neck Cancer
Shozo Okamoto, Tohru Shiga, Koichi Yasuda, Yoichi M. Ito, Keiichi Magota, Katsuhiko Kasai, Yuji Kuge, Hiroki Shirato, Nagara Tamaki
JOURNAL OF NUCLEAR MEDICINE, 54, 2, 201, 207, 2013年02月, ［査読有り］
英語, 研究論文（学術雑誌）

Arterial (18)F-fluorodeoxyglucose uptake reflects balloon catheter-induced thrombus formation and tissue factor expression via nuclear factor-κB in rabbit atherosclerotic lesions.
Yamashita A, Zhao Y, Zhao S, Matsuura Y, Sugita C, Iwakiri T, Okuyama N, Ohe K, Koshimoto C, Kawai K, Tamaki N, Kuge Y, Asada Y
Circulation Journal, 77, 10, 2626, 2635, 2013年, ［査読有り］
英語, 研究論文（学術雑誌）

Bone marrow stromal cell transplantation enhances recovery of local glucose metabolism after cerebral infarction in rats: A serial 18F-FDG PET study
Michiyuki Miyamoto, Satoshi Kuroda, Songji Zhao, Keiichi Magota, Hideo Shichinohe, Kiyohiro Houkin, Yuji Kuge, Nagara Tamaki
Journal of Nuclear Medicine, 54, 1, 145, 150, 2013年01月, ［査読有り］
英語, 研究論文（学術雑誌）

Pathophysiological characteristics of melanoma in-transit metastasis in a lymphedema mouse model
Kohei Oashi, Hiroshi Furukawa, Hiroshi Nishihara, Michitaka Ozaki, Akihiko Oyama, Emi Funayama, Toshihiko Hayashi, Yuji Kuge, Yuhei Yamamoto
Journal of Investigative Dermatology, 133, 2, 537, 544, Nature Publishing Group, 2013年, ［査読有り］
英語, 研究論文（学術雑誌）

[ (18)F]fluoromisonidazole and a New PET System With Semiconductor Detectors and a Depth of Interaction System for Intensity Modulated Radiation Therapy for Nasopharyngeal Cancer.
Yasuda K, Onimaru R, Okamoto S, Shiga T, Katoh N, Tsuchiya K, Suzuki R, Takeuchi W, Kuge Y, Tamaki N, Shirato H
Int J Radiat Oncol Biol Phys., 85, 1, 142, 7, 2013年, ［査読有り］

Ferrous Ferric Chloride Downregulates the Inflammatory Response to Rhodococcus aurantiacus Infection in Mice
Yimin, Huirong Tao, Masashi Kohanawa, Songji Zhao, Yuji Kuge, Nagara Tamaki
BIOLOGICAL & PHARMACEUTICAL BULLETIN, 35, 12, 2214, 2223, 2012年12月, ［査読有り］
英語, 研究論文（学術雑誌）

(11)C-Methionine positron emission tomography may monitor the activity of encephalitis.
Kenji Hirata, Tohru Shiga, Noriyuki Fujima, Osamu Manabe, Reiko Usui, Yuji Kuge, Nagara Tamaki
Acta radiologica (Stockholm, Sweden : 1987), 53, 10, 1155, 7, 2012年12月01日, ［査読有り］, ［国際誌］
英語, Encephalitis is generally diagnosed by clinical symptoms, cerebrospinal fluid examination, and imaging studies including CT, magnetic resonance imaging (MRI), and perfusion single photon emission tomography (SPECT). However, the role of positron emission tomography (PET) in diagnosis of encephalitis remains unclear. A 49-year-old woman presenting with coma and elevated inflammatory reaction was diagnosed as having encephalitis according to slow activity on electroencephalogram, broad cortical lesion in MR fluid attenuated inversion recovery image, and increased blood flow demonstrated by SPECT. PET revealed increased accumulation of (11)C-methionine (MET) in the affected brain tissues. After the symptom had improved 2 months later, the accumulation of MET as well as the abnormal findings of MR imaging and SPECT was normalized. This case indicated that MET PET may monitor the activity of encephalitis.

Evaluation of changes in the tumor microenvironment after sorafenib therapy by sequential histology and F-18-fluoromisonidazole hypoxia imaging in renal cell carcinoma
Masahiro Murakami, Songji Zhao, Yan Zhao, Nusrat Fatema Chowdhury, Wenwen Yu, Ken-Ichi Nishijima, Mitsuyoshi Takiguchi, Nagara Tamaki, Yuji Kuge
INTERNATIONAL JOURNAL OF ONCOLOGY, 41, 5, 1593, 1600, 2012年11月, ［査読有り］
英語, 研究論文（学術雑誌）

Quantitative Determination of Apoptosis of Pancreatic β-Cells in a Murine Model of Type 1 Diabetes Mellitus.
Watanabe A, Nishijima KI, Zhao S, Zhao Y, Tanaka Y, Takemoto H, Strauss HW, Blankenberg FG, Tamaki N, Kuge Y
J Nucl Med., 53, 10, 1585, 1591, 2012年10月, ［査読有り］
英語, 研究論文（学術雑誌）

Cardiac β-adrenergic receptor density and myocardial systolic function in the remote noninfarcted region after prior myocardial infarction with left ventricular remodelling.
Ohte N, Narita H, Iida A, Fukuta H, Iizuka N, Hayano J, Kuge Y, Tamaki N, Kimura G
Eur J Nucl Med Mol Imaging., 39, 8, 1246, 1253, 2012年08月, ［査読有り］
英語, 研究論文（学術雑誌）

Norepinephrine Transporter Imaging in the Brain of a Rat Model of Depression Using Radioiodinated (2S, αS)-2-(α-(2-iodophenoxy)benzyl)morpholine.
Kanegawa N, Kiyono Y, Sugitaa T, Kuge Y, Fujibayasi Y, Saji H
Mol Imaging., 11, 4, 280, 285, 2012年07月, ［査読有り］
英語, 研究論文（学術雑誌）

Intracerebral, but not intravenous, transplantation of bone marrow stromal cells enhances functional recovery in rat cerebral infarct: An optical imaging study
Masahito Kawabori, Satoshi Kuroda, Taku Sugiyama, Masaki Ito, Hideo Shichinohe, Kiyohiro Houkin, Yuji Kuge, Nagara Tamaki
NEUROPATHOLOGY, 32, 3, 217, 226, 2012年06月, ［査読有り］
英語, 研究論文（学術雑誌）

F-18-Fluoromisonidazole positron emission tomography may differentiate glioblastoma multiforme from less malignant gliomas
Kenji Hirata, Shunsuke Terasaka, Tohru Shiga, Naoya Hattori, Keiichi Magota, Hiroyuki Kobayashi, Shigeru Yamaguchi, Kiyohiro Houkin, Shinya Tanaka, Yuji Kuge, Nagara Tamaki
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, 39, 5, 760, 770, 2012年05月, ［査読有り］
英語, 研究論文（学術雑誌）

Writing errors in ALS related to loss of neuronal integrity in the anterior cingulate gyrus
Ichiro Yabe, Sachiko Tsuji-Akimoto, Tohru Shiga, Shinsuke Hamada, Kenji Hirata, Mika Otsuki, Yuji Kuge, Nagara Tamaki, Hidenao Sasaki
JOURNAL OF THE NEUROLOGICAL SCIENCES, 315, 1-2, 55, 59, 2012年04月, ［査読有り］
英語, 研究論文（学術雑誌）

Therapeutic effects of intra-arterial delivery of bone marrow stromal cells in traumatic brain injury of rats--in vivo cell tracking study by near-infrared fluorescence imaging.
Toshiya Osanai, Satoshi Kuroda, Taku Sugiyama, Masahito Kawabori, Masaki Ito, Hideo Shichinohe, Yuji Kuge, Kiyohiro Houkin, Nagara Tamaki, Yoshinobu Iwasaki
Neurosurgery, 70, 2, 435, 44, 2012年02月, ［査読有り］, ［国際誌］
英語, BACKGROUND: A noninvasive and effective route of cell delivery should be established to yield maximal therapeutic effects for central nervous system (CNS) disorders. OBJECTIVE: To elucidate whether intra-arterial delivery of bone marrow stromal cells (BMSCs) significantly promotes functional recovery in traumatic brain injury (TBI) in rats. METHODS: Rat BMSCs were transplanted through the ipsilateral internal carotid artery 7 days after the onset of cortical freezing injury. The BMSCs were labeled with fluorescent dye, and in vivo optical imaging was employed to monitor the behaviors of cells for 4 weeks after transplantation. Motor function was assessed for 4 weeks, and the transplanted BMSCs were examined using immunohistochemistry. RESULTS: In vivo optical imaging and histologic analysis clearly demonstrated that the intra-arterially injected BMSCs were engrafted during the first pass without systemic circulation, and the transplanted BMSCs started to migrate from the cerebral capillary bed to the injured CNS tissue within 3 hours. Intra-arterial BMSC transplantation significantly promoted functional recovery after cortical freezing injury. A subgroup of BMSCs expressed the phenotypes of neurons, astrocytes, and endothelial cells around the injured neocortex 4 weeks after transplantation. CONCLUSION: Intra-arterial transplantation may be a valuable option for prompt, noninvasive delivery of BMSCs to the injured CNS tissue, enhancing functional recovery after TBI. In vivo optical imaging may provide important information on the intracerebral behaviors of donor cells by noninvasive, serial visualization.

A novel murine model for non-alcoholic steatohepatitis developed by combination of a high-fat diet and oxidized low-density lipoprotein
Yin Lin, Hiroaki Furumaki, Shiho Matsuoka, Toshihiro Sakurai, Masashi Kohanawa, Songji Zhao, Yuji Kuge, Nagara Tamaki, Hitoshi Chiba
LABORATORY INVESTIGATION, 92, 2, 265, 281, 2012年02月, ［査読有り］
英語, 研究論文（学術雑誌）

Effect of glycosylation on biodistribution of radiolabeled glucagon-like peptide 1
Ayahisa Watanabe, Ken-ichi Nishijima, Songji Zhao, Yoshikazu Tanaka, Takeshi Itoh, Hiroshi Takemoto, Nagara Tamaki, Yuji Kuge
ANNALS OF NUCLEAR MEDICINE, 26, 2, 184, 191, 2012年02月, ［査読有り］
英語, 研究論文（学術雑誌）

A Pre-targeting Strategy for MR Imaging of Functional Molecules Using Dendritic Gd-Based Contrast Agents
Kohei Sano, Takashi Temma, Takashi Azuma, Ryusuke Nakai, Michiko Narazaki, Yuji Kuge, Hideo Saji
MOLECULAR IMAGING AND BIOLOGY, 13, 6, 1196, 1203, 2011年12月, ［査読有り］
英語, 研究論文（学術雑誌）

Radiolabeled uracil derivative as a novel SPECT probe for thymidine phosphorylase: suppressed accumulation into tumor cells by target gene knockdown
Hua Li, Songji Zhao, Yongnan Jin, Ken-ichi Nishijima, Hiromichi Akizawa, Kazue Ohkura, Nagara Tamaki, Yuji Kuge
NUCLEAR MEDICINE COMMUNICATIONS, 32, 12, 1211, 1215, 2011年12月, ［査読有り］
英語, 研究論文（学術雑誌）

Dynamic C-11-methionine PET analysis has an additional value for differentiating malignant tumors from granulomas: an experimental study using small animal PET
Songji Zhao, Yuji Kuge, Min Yi, Yan Zhao, Toshiyuki Hatano, Keiichi Magota, Ken-ichi Nishijima, Masashi Kohanawa, Nagara Tamaki
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, 38, 10, 1876, 1886, 2011年10月, ［査読有り］
英語, 研究論文（学術雑誌）

PET Imaging of Hypoxia-Inducible Factor-1-Active Tumor Cells with Pretargeted Oxygen-Dependent Degradable Streptavidin and a Novel F-18-Labeled Biotin Derivative
Takashi Kudo, Masashi Ueda, Hiroaki Konishi, Hidekazu Kawashima, Yuji Kuge, Takahiro Mukai, Azusa Miyano, Shotaro Tanaka, Shinae Kizaka-Kondoh, Masahiro Hiraoka, Hideo Saji
MOLECULAR IMAGING AND BIOLOGY, 13, 5, 1003, 1010, 2011年10月, ［査読有り］
英語, 研究論文（学術雑誌）

F-18-Fluorothymidine PET/CT as an early predictor of tumor response to treatment with cetuximab in human lung cancer xenografts
Satoshi Takeuchi, Songji Zhao, Yuji Kuge, Yan Zhao, Ken-Ichi Nishijima, Toshiyuki Hatano, Yasushi Shimizu, Ichiro Kinoshita, Nagara Tamaki, Hirotoshi Dosaka-Akita
ONCOLOGY REPORTS, 26, 3, 725, 730, 2011年09月, ［査読有り］
英語, 研究論文（学術雑誌）

Localization of Deoxyglucose and Annexin A5 in Experimental Atheroma Correlates with Macrophage Infiltration but not Lipid Deposition in the Lesion
Yan Zhao, Songji Zhao, Yuji Kuge, William H. Strauss, Francis G. Blankenberg, Nagara Tamaki
MOLECULAR IMAGING AND BIOLOGY, 13, 4, 712, 720, 2011年08月, ［査読有り］
英語, 研究論文（学術雑誌）

Gene and protein analysis of brain derived neurotrophic factor expression in relation to neurological recovery induced by an enriched environment in a rat stroke model
Kenji Hirata, Yuji Kuge, Chiaki Yokota, Akina Harada, Koichi Kokame, Hiroyasu Inoue, Hidekazu Kawashima, Hiroko Hanzawa, Yuji Shono, Hideo Saji, Kazuo Minematsu, Nagara Tamaki
NEUROSCIENCE LETTERS, 495, 3, 210, 215, 2011年05月, ［査読有り］
英語, 研究論文（学術雑誌）

Performance characterization of the Inveon preclinical small-animal PET/SPECT/CT system for multimodality imaging
Keiichi Magota, Naoki Kubo, Yuji Kuge, Ken-ichi Nishijima, Songji Zhao, Nagara Tamaki
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, 38, 4, 742, 752, 2011年04月, ［査読有り］
英語, 研究論文（学術雑誌）

Semiquantitative analysis of C-11 methionine PET may distinguish brain tumor recurrence from radiation necrosis even in small lesions
Shozo Okamoto, Tohru Shiga, Naoya Hattori, Naoki Kubo, Toshiki Takei, Norio Katoh, Yutaka Sawamura, Kenichi Nishijima, Yuji Kuge, Nagara Tamaki
ANNALS OF NUCLEAR MEDICINE, 25, 3, 213, 220, 2011年04月, ［査読有り］
英語, 研究論文（学術雑誌）

Near-Infrared Fluorescence Labeling Allows Noninvasive Tracking of Bone Marrow Stromal Cells Transplanted Into Rat Infarct Brain
Taku Sugiyama, Satoshi Kuroda, Toshiya Osanai, Hideo Shichinohe, Yuji Kuge, Masaki Ito, Masahito Kawabori, Yoshinobu Iwasaki
NEUROSURGERY, 68, 4, 1036, 1047, 2011年04月, ［査読有り］
英語, 研究論文（学術雑誌）

Gene expression associated with an enriched environment after transient focal ischemia
Yuji Shono, Chiaki Yokota, Yuji Kuge, Shinsuke Kido, Akina Harada, Koichi Kokame, Hiroyasu Inoue, Mariko Hotta, Kenji Hirata, Hideo Saji, Nagara Tamaki, Kazuo Minematsu
BRAIN RESEARCH, 1376, 60, 65, 2011年02月, ［査読有り］
英語, 研究論文（学術雑誌）

Regional partition coefficient of water in patients with cerebrovascular disease and its effect on rCBF assessment
Kenji Hirata, Naoya Hattori, Chietsugu Katoh, Tohru Shiga, Satoshi Kuroda, Naoki Kubo, Reiko Usui, Yuji Kuge, Nagara Tamaki
NUCLEAR MEDICINE COMMUNICATIONS, 32, 1, 63, 70, 2011年01月, ［査読有り］
英語, 研究論文（学術雑誌）

Tissue Factor Detection for Selectively Discriminating Unstable Plaques in an Atherosclerotic Rabbit Model
Takashi Temma, Yuki Ogawa, Yuji Kuge, Seigo Ishino, Nozomi Takai, Kantaro Nishigori, Masashi Shiomi, Masahiro Ono, Hideo Saji
JOURNAL OF NUCLEAR MEDICINE, 51, 12, 1979, 1986, 2010年12月, ［査読有り］
英語, 研究論文（学術雑誌）

Imaging with radiolabelled anti-membrane type 1 matrix metalloproteinase (MT1-MMP) antibody: potentials for characterizing atherosclerotic plaques
Yuji Kuge, Nozomi Takai, Yuki Ogawa, Takashi Temma, Yan Zhao, Kantaro Nishigori, Seigo Ishino, Junko Kamihashi, Yasushi Kiyono, Masashi Shiomi, Hideo Saji
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, 37, 11, 2093, 2104, 2010年11月, ［査読有り］
英語, 研究論文（学術雑誌）

Radioimmunodetection of Membrane Type-1 Matrix Metalloproteinase Relevant to Tumor Malignancy with a Pre-targeting Method
Kohei Sano, Takashi Temma, Yuji Kuge, Takashi Kudo, Junko Kamihashi, Songji Zhao, Hideo Saji
BIOLOGICAL & PHARMACEUTICAL BULLETIN, 33, 9, 1589, 1595, 2010年09月, ［査読有り］
英語, 研究論文（学術雑誌）

Rapid detection of hypoxia-inducible factor-1-active tumours: pretargeted imaging with a protein degrading in a mechanism similar to hypoxia-inducible factor-1 alpha
Masashi Ueda, Takashi Kudo, Yuji Kuge, Takahiro Mukai, Shotaro Tanaka, Hiroaki Konishi, Azusa Miyano, Masahiro Ono, Shinae Kizaka-Kondoh, Masahiro Hiraoka, Hideo Saji
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, 37, 8, 1566, 1574, 2010年08月, ［査読有り］
英語, 研究論文（学術雑誌）

In vitro and in vivo evaluations of a radioiodinated thymidine phosphorylase inhibitor as a tumor diagnostic agent for angiogenic enzyme imaging
Hiromichi Akizawa, Songji Zhao, Masayuki Takahashi, Ken-ichi Nishijima, Yuji Kuge, Nagara Tamaki, Koh-ichi Seki, Kazue Ohkura
NUCLEAR MEDICINE AND BIOLOGY, 37, 4, 427, 432, 2010年05月, ［査読有り］
英語, 研究論文（学術雑誌）

Isolation and identification of new vasodilative substances in diesel exhaust particles
Koh-ichi Seki, Yoichi Noya, Yusuke Mikami, Shinji Taneda, Akira K. Suzuki, Yuji Kuge, Kazue Ohkura
ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH, 17, 3, 717, 723, 2010年03月, ［査読有り］
英語, 研究論文（学術雑誌）

Nicotinic acetylcholine receptors expressed in the ventralposterolateral thalamic nucleus play an important role in anti-allodynic effects
M. Ueda, Y. Iida, A. Tominaga, T. Yoneyama, M. Ogawa, Y. Magata, H. Nishimura, Y. Kuge, H. Saji
BRITISH JOURNAL OF PHARMACOLOGY, 159, 6, 1201, 1210, 2010年03月, ［査読有り］
英語, 研究論文（学術雑誌）

Synthesis of a New NIR Fluorescent Nd Complex Labeling Agent
Kazuki Aita, Takashi Temma, Yoichi Shimizu, Yuji Kuge, Koh-ichi Seki, Hideo Saji
JOURNAL OF FLUORESCENCE, 20, 1, 225, 234, 2010年01月, ［査読有り］
英語, 研究論文（学術雑誌）

NIR fluorescent ytterbium compound for in vivo fluorescence molecular imaging
Kazuki Aita, Takashi Temma, Yuji Kuge, Koh-ichi Seki, Hideo Saji
LUMINESCENCE, 25, 1, 19, 24, 2010年01月, ［査読有り］
英語, 研究論文（学術雑誌）

Synthesis and evaluation of a radioiodinated lumiracoxib derivative for the imaging of cyclooxygenase-2 expression
Yuji Kuge, Naoyuki Obokata, Hiroyuki Kimura, Yumiko Katada, Takashi Temma, Yukihiko Sugimoto, Kazuki Aita, Koh-ichi Seki, Nagara Tamaki, Hideo Saji
NUCLEAR MEDICINE AND BIOLOGY, 36, 8, 869, 876, 2009年11月, ［査読有り］
英語, 研究論文（学術雑誌）

Clinical Value and Limitations of [C-11]-Methionine PET for Detection and Localization of Suspected Parathyroid Adenomas
Ken Herrmann, Toshiki Takei, Kakuko Kanegae, Tohru Shiga, Andreas K. Buck, Jennifer Altomonte, Markus Schwaiger, Tibor Schuster, Kenichi Nishijima, Yuji Kuge, Nagara Tamaki
MOLECULAR IMAGING AND BIOLOGY, 11, 5, 356, 363, 2009年09月, ［査読有り］
英語, 研究論文（学術雑誌）

Development of a Radiolabeled Probe for Detecting Membrane Type-1 Matrix Metalloproteinase on Malignant Tumors
Takashi Temma, Kohei Sano, Yuji Kuge, Junko Kamihashi, Nozomi Takai, Yuki Ogawa, Hideo Saji
BIOLOGICAL & PHARMACEUTICAL BULLETIN, 32, 7, 1272, 1277, 2009年07月, ［査読有り］
英語, 研究論文（学術雑誌）

Imaging of HIF-1-Active Tumor Hypoxia Using a Protein Effectively Delivered to and Specifically Stabilized in HIF-1-Active Tumor Cells
Takashi Kudo, Masashi Ueda, Yuji Kuge, Takahiro Mukai, Shotaro Tanaka, Maki Masutani, Yasushi Kiyono, Shinae Kizaka-Kondoh, Masahiro Hiraoka, Hideo Saji
JOURNAL OF NUCLEAR MEDICINE, 50, 6, 942, 949, 2009年06月, ［査読有り］
英語, 研究論文（学術雑誌）

New [¹¹C]phosgene based synthesis of [¹¹C]pyrimidines for positron emission tomography
Koh Ichi Seki, Ken Ichi Nishijima, Kimihito Sanoki, Yuji Kuge, Masayuki Takahashi, Hiromichi Akizawa, Nagara Tamaki, Leonard I. Wiebe, Kazue Ohkura
Heterocycles, 77, 2, 1307, 1321, 2009年02月01日, ［査読有り］
研究論文（学術雑誌）

Myocardial beta-Adrenergic Receptor Density Assessed by (11)C-CGP12177 PET Predicts Improvement of Cardiac Function After Carvedilol Treatment in Patients with Idiopathic Dilated Cardiomyopathy
Masanao Naya, Takahiro Tsukamoto, Koichi Morita, Chietsugu Katoh, Kenichi Nishijima, Hiroshi Komatsu, Satoshi Yamada, Yuji Kuge, Nagara Tamaki, Hiroyuki Tsutsui
JOURNAL OF NUCLEAR MEDICINE, 50, 2, 220, 225, 2009年02月, ［査読有り］
英語, 研究論文（学術雑誌）

Mutual modulation between interleukin-10 and interleukin-6 induced by Rhodococcus aurantiacus infection in mice
Yimin, Masashi Kohanawa, Michitaka Ozaki, Sanae Haga, Keiko Fujikawa, Songji Zhao, Yuji Kuge, Nagara Tamaki
MICROBES AND INFECTION, 10, 14-15, 1450, 1458, 2008年11月, ［査読有り］
英語, 研究論文（学術雑誌）

Synthesis of a radioiodinated thymidine phosphorylase inhibitor and its preliminary evaluation as a potential SPECT tracer for angiogenic enzyme expression
Masayuki Takahashi, Koh-ichi Seki, Ken-ichi Nishijima, Songji Zhao, Yuji Kuge, Nagara Tamaki, Kazue Ohkura
JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS, 51, 11-12, 384, 387, 2008年10月, ［査読有り］
英語, 研究論文（学術雑誌）

Prolonged High-Fat Feeding Enhances Aortic F-18-FDG and Tc-99m-Annexin A5 Uptake in Apolipoprotein E-Deficient and Wild-Type C57BL/6J Mice
Yan Zhao, Yuji Kuge, Songji Zhao, H. William Strauss, Francis G. Blankenberg, Nagara Tamaki
JOURNAL OF NUCLEAR MEDICINE, 49, 10, 1707, 1714, 2008年10月, ［査読有り］
英語, 研究論文（学術雑誌）

Targeting of Lectinlike Oxidized Low-Density Lipoprotein Receptor 1 (LOX-1) with (99m)TCLabeled Anti-LOX-1 Antibody: Potential Agent for Imaging of Vulnerable Plaque
Seigo Ishino, Takahiro Mukai, Yuji Kuge, Noriaki Kume, Mikako Ogawa, Nozomi Takai, Junko Kamihashi, Masashi Shiomi, Manabu Minami, Toru Kita, Hideo Saji
JOURNAL OF NUCLEAR MEDICINE, 49, 10, 1677, 1685, 2008年10月, ［査読有り］
英語, 研究論文（学術雑誌）

SYNTHESIS OF C-11-LABELED URACIL DERIVATIVE FOR A PET TRACER TARGETING THYMIDINE PHOSPHORYLASE
Masayuki Takahashi, Koh-ichi Seki, Ken-ichi Nishijima, Yuji Kuge, Nagara Tamaki, Kazue Ohkura
HETEROCYCLES, 76, 1, 237, 241, 2008年09月, ［査読有り］
英語, 研究論文（学術雑誌）

Prominent lectin-like oxidized low density lipoprotein (LDL) receptor-1 (LOX-1) expression in atherosclerotic lesions is associated with tissue factor expression and apoptosis in hypercholesterolemic rabbits
Yuji Kuge, Noriaki Kume, Scigo Ishino, Nozomi Takai, Yuki Ogawa, Takahiro Mukai, Manabu Minami, Masashi Shiomi, Hideo Saji
BIOLOGICAL & PHARMACEUTICAL BULLETIN, 31, 8, 1475, 1482, 2008年08月, ［査読有り］
英語, 研究論文（学術雑誌）

PET 0-15 cerebral blood flow and metabolism after acute stroke in spontaneously hypertensive rats
Takashi Temma, Yuji Kuge, Kohei Sano, Junko Kamihashi, Naoyuki Obokata, Hidekazu Kawashima, Yasuhiro Magata, Hideo Saji
BRAIN RESEARCH, 1212, 18, 24, 2008年05月, ［査読有り］
英語, 研究論文（学術雑誌）

Heterogeneous reduction of myocardial oxidative metabolism in patients with ischemic and dilated cardiomyopathy using C-11 acetate PET
Yen-Wen Wu, Masanao Naya, Takahiro Tsukamoto, Hiroshi Komatsu, Koichi Morita, Keiichiro Yoshinaga, Yuji Kuge, Hiroyuki Tsutsui, Nagara Tamaki
CIRCULATION JOURNAL, 72, 5, 786, 792, 2008年05月, ［査読有り］
英語, 研究論文（学術雑誌）

Evaluation of radioiodinated (2S,alpha S)-2-(alpha-(2-iodophenoxy)benzyl) morpholine as a radioligand for imaging of norepinephrine transporter in the heart
Yasushi Kiyono, Taku Sugita, Masashi Ueda, Hidekazu Kawashima, Naoki Kanegawa, Yuji Kuge, Yasuhisa Fujibayashi, Hideo Saji
NUCLEAR MEDICINE AND BIOLOGY, 35, 2, 213, 218, 2008年02月, ［査読有り］
英語, 研究論文（学術雑誌）

Usefulness of C-11-methionine for differentiating tumors from granulomas in experimental rat models: A comparison with F-18-FDG and F-18-FLT
Songji Zhao, Yuji Kuge, Masashi Kohanawa, Toshiyuki Takahashi, Yan Zhao, Min Yi, Kakuko Kanegae, Koh-ichi Seki, Nagara Tamaki
JOURNAL OF NUCLEAR MEDICINE, 49, 1, 135, 141, 2008年01月, ［査読有り］
英語, 研究論文（学術雑誌）

Extensive FDG uptake and its modification with corticosteroid in a granuloma rat model: an experimental study for differentiating granuloma from tumors
Songji Zhao, Yuji Kuge, Masashi Kohanawa, Toshiyuki Takahashi, Hidekazu Kawashima, Takashi Temma, Toshiki Takei, Yan Zhao, Koh-ichi Seki, Nagara Tamaki
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, 34, 12, 2096, 2105, 2007年12月, ［査読有り］
英語, 研究論文（学術雑誌）

Decreased myocardial beta-adrenergic receptor density in relation to increased sympathetic tone in patients with nonischemic cardiomyopathy
Takahiro Tsukamoto, Koichi Morita, Masanao Naya, Masayuki Inubushi, Chietsugu Katoh, Kenichi Nishijima, Yuji Kuge, Hiroshi Okamoto, Hiroyuki Tsutsui, Nagara Tamaki
JOURNAL OF NUCLEAR MEDICINE, 48, 11, 1777, 1782, 2007年11月, ［査読有り］
英語, 研究論文（学術雑誌）

Comparison of Tc-99m-annexin A5 with F-18-FDG for the detection of atherosclerosis in ApoE-/- mice
Yan Zhao, Yuji Kuge, Songji Zhao, Koichi Morita, Masayuki Inubushi, H. William Strauss, Francis G. Blankenberg, Nagara Tamaki
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, 34, 11, 1747, 1755, 2007年11月, ［査読有り］
英語, 研究論文（学術雑誌）

Lectin-like oxidized LDL receptor-1 (LOX-1) expression is associated with atherosclerotic plaque instability-analysis in hypercholesterolemic rabbits
Seigo Ishino, Takahiro Mukai, Noriaki Kume, Daigo Asano, Mikako Ogawa, Yuji Kuge, Manabu Minami, Toru Kita, Masashi Shiomi, Hideo Saji
ATHEROSCLEROSIS, 195, 1, 48, 56, 2007年11月, ［査読有り］
英語, 研究論文（学術雑誌）

All-trans retinoic acid enhances murine dendritic cell migration to draining lymph nodes via the balance of matrix metalloproteinases and their inhibitors
Stephanie Darmanin, Jian Chen, Songji Zhao, Hongyan Cui, Reza Shirkoohi, Naoki Kubo, Yuji Kuge, Nagara Tamaki, Koji Nakagawa, Jun-Ichi Hamada, Tetsuya Moriuchi, Masanobu Kobayashi
JOURNAL OF IMMUNOLOGY, 179, 7, 4616, 4625, 2007年10月, ［査読有り］
英語, 研究論文（学術雑誌）

Distribution profiles of membrane type-1 matrix metalloproteinase (MT1-MMP), matrix metalloproteinase-2 (MMP-2) and cyclooxygenase-2 (COX-2) in rabbit atherosclerosis: Comparison with plaque instability analysis
Yuji Kuge, Nozomi Takai, Seigo Ishino, Takashi Temma, Masashi Shiomi, Hideo Saji
Biological and Pharmaceutical Bulletin, 30, 9, 1634, 1640, 2007年09月, ［査読有り］
英語, 研究論文（学術雑誌）

Applicability of a high-resolution small semiconductor gamma camera to small animal imaging
Yasushi Kiyono, Yuji Kuge, Yumiko Katada, Hidekazu Kawashima, Yasuhiro Magata, Hideo Saji
NUCLEAR MEDICINE COMMUNICATIONS, 28, 9, 736, 741, 2007年09月, ［査読有り］
英語, 研究論文（学術雑誌）

Development of a novel neodymium compound for in vivo fluorescence imaging
Kazuki Aita, Takashi Temma, Yuji Kuge, Hideo Saji
LUMINESCENCE, 22, 5, 455, 461, 2007年09月, ［査読有り］
英語, 研究論文（学術雑誌）

Comparison of MET-PET and FDG-PET for differentiation between benign lesions and lung cancer in pneumoconiosis
Kakuko Kanegae, Ikuo Nakano, Kiyonobu Kimura, Hiroshi Kaji, Yuji Kuge, Tohru Shiga, Songji Zhao, Shouzo Okamoto, Nagara Tamaki
ANNALS OF NUCLEAR MEDICINE, 21, 6, 331, 337, 2007年08月, ［査読有り］
英語, 研究論文（学術雑誌）

Tc-99m-Annexin A5 for noninvasive characterization of atherosclerotic lesions: imaging and histological studies in myocardial infarction-prone Watanabe heritable hyperlipidemic rabbits
Seigo Ishino, Yuji Kuge, Nozomi Takai, Nagara Tamaki, H. William Strauss, Francis G. Blankenberg, Masashi Shiomi, Hideo Saji
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, 34, 6, 889, 899, 2007年06月, ［査読有り］
英語, 研究論文（学術雑誌）

A novel and efficient synthesis of [2-C-11]5-fluorouracil for prognosis of cancer chemotherapy
Koh-ichi Seki, Ken-ichi Nishijima, Yuji Kuge, Nagara Tamaki, Leonard I. Wiebe, Kazue Ohkura
JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES, 10, 2, 212, 216, 2007年06月, ［査読有り］
英語, 研究論文（学術雑誌）

Is MIBG a substrate of P-glycoprotein?
Yasushi Kiyono, Tomoko Yamashita, Hisako Doi, Yuji Kuge, Toshiya Katsura, Ken-Ichi Inui, Hideo Saji
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, 34, 4, 448, 452, 2007年04月, ［査読有り］
英語, 研究論文（学術雑誌）

Smoking cessation normalizes coronary endothelial vasomotor response assessed with O-15-water and PET in healthy young smokers
Koichi Morita, Takahiro Tsukamoto, Masanao Naya, Kazuyuki Noriyasu, Masayuki Inubushi, Tohru Shiga, Chietsugu Katoh, Yuji Kuge, Hiroyuki Tsutsui, Nagara Tamaki
JOURNAL OF NUCLEAR MEDICINE, 47, 12, 1914, 1920, 2006年12月, ［査読有り］
英語, 研究論文（学術雑誌）

Photochemical synthesis of polycyclic pyrimidines through the acid catalyzed cycloaddition of 6-chloro-1-methyluracil to methyl substituted benzenes
Kazue Ohkura, Takeshi Yamaguchi, Ken-ichi Nishijima, Yuji Kuge, Koh-ichi Seki
HETEROCYCLES, 70, 501, +, 2006年12月, ［査読有り］
英語, 研究論文（学術雑誌）

Estimation of oxygen metabolism in a rat model of permanent ischemia using positron emission tomography with injectable O-15-O-2
Takashi Temma, Yasuhiro Magata, Yuji Kuge, Sayaka Shimonaka, Kohei Sano, Yumiko Katada, Hidekazu Kawashima, Takahiro Mukai, Hiroshi Watabe, Hidehiro Iida, Hideo Saji
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 26, 12, 1577, 1583, 2006年12月, ［査読有り］
英語, 研究論文（学術雑誌）

Myocardial flow reserve is influenced by both coronary artery stenosis severity and coronary risk factors in patients with suspected coronary artery disease
Takahiro Tsukamoto, Koichi Morita, Masanao Naya, Chietsugu Katoh, Masayuki Inubushi, Yuji Kuge, Hiroyuki Tsutsui, Nagara Tamaki
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, 33, 10, 1150, 1156, 2006年10月, ［査読有り］
英語, 研究論文（学術雑誌）

A new convenient method for the synthesis of [2-C-11]thymine utilizing [C-11]phosgene
Kazue Ohkura, Ken-ichi Nishijima, Kimihito Sanoki, Yuji Kuge, Nagara Tamaki, Koh-ichi Seki
TETRAHEDRON LETTERS, 47, 30, 5321, 5323, 2006年07月, ［査読有り］
英語, 研究論文（学術雑誌）

Loss of neuronal integrity: a cause of hypometabolism in patients with traumatic brain injury without MRI abnormality in the chronic stage
T Shiga, K Ikoma, C Katoh, H Isoyama, T Matsuyama, Y Kuge, H Kageyama, T Kohno, S Terae, N Tamaki
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, 33, 7, 817, 822, 2006年07月, ［査読有り］
英語, 研究論文（学術雑誌）

Synthesis and evaluation of radioiodinated (S,S)-2-(alpha-(2-iodophenoxy)benzyl)morpholine for imaging brain norepinephrine transporter
Naoki Kanegawa, Yasushi Kiyono, Hiroyuki Kimura, Taku Sugita, Satomi Kajiyama, Hidekazu Kawashima, Masashi Ueda, Yuji Kuge, Hideo Saji
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, 33, 6, 639, 647, 2006年06月, ［査読有り］
英語, 研究論文（学術雑誌）

Change of central cholinergic receptors following lesions of nucleus basalis magnocellularis in rats: search for an imaging index suitable for the early detection of Alzheimer's disease
M Ogawa, Y Iida, M Nakagawa, Y Kuge, H Kawashima, A Tominaga, M Ueda, Y Magata, H Saji
NUCLEAR MEDICINE AND BIOLOGY, 33, 2, 249, 254, 2006年02月, ［査読有り］
英語, 研究論文（学術雑誌）

Synthesis and evaluation of radioiodinated cyclooxygenase-2 inhibitors as potential SPECT tracers for cyclooxygenase-2 expression
Y Kuge, Y Katada, S Shimonaka, T Temma, H Kimura, Y Kiyono, C Yokota, K Minematsu, K Seki, N Tamaki, K Ohkura, H Saji
NUCLEAR MEDICINE AND BIOLOGY, 33, 1, 21, 27, 2006年01月, ［査読有り］
英語, 研究論文（学術雑誌）

Evaluating performance of a pixel array semiconductor SPECT system for small animal imaging
N Kubo, S Zhao, Y Fujiki, A Kinda, N Motomura, C Katoh, T Shiga, H Kawashima, Y Kuge, N Tamaki
ANNALS OF NUCLEAR MEDICINE, 19, 7, 633, 639, 2005年10月, ［査読有り］
英語, 研究論文（学術雑誌）

Quantitative analysis of myocardial glucose utilization in patients with left ventricular dysfunction by means of F-18-FDG dynamic positron tomography and three-compartment analysis
K Morita, C Katoh, K Yoshinaga, K Noriyasu, M Mabuchi, T Tsukamoto, H Kageyama, T Shiga, Y Kuge, N Tamaki
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, 32, 7, 806, 812, 2005年07月, ［査読有り］
英語, 研究論文（学術雑誌）

Bilateral induction of the S-100A9 gene in response to spreading depression is modulated by the cyclooxygenase-2 activity
C Yokota, Y Kuge, H Inoue, N Tamaki, K Minematsu
JOURNAL OF THE NEUROLOGICAL SCIENCES, 234, 1-2, 11, 16, 2005年07月, ［査読有り］
英語, 研究論文（学術雑誌）

Aggravation of hemorrhagic transformation by early intraarterial infusion of low-dose vascular endothelial growth factor after transient focal cerebral ischemia in rats
T Abumiya, C Yokota, Y Kuge, K Minematsu
BRAIN RESEARCH, 1049, 1, 95, 103, 2005年07月, ［査読有り］
英語, 研究論文（学術雑誌）

Enhanced apoptotic reaction correlates with suppressed tumor glucose utilization after cytotoxic chemotherapy: Use of Tc-99m-annexin V, F-18-FDG, and histologic evaluation
T Takei, Y Kuge, S Zhao, M Sato, HW Strauss, FG Blankenberg, JF Tait, N Tamaki
JOURNAL OF NUCLEAR MEDICINE, 46, 5, 794, 799, 2005年05月, ［査読有り］
英語, 研究論文（学術雑誌）

Biologic correlates of intratumoral heterogeneity in F-18-FDG distribution with regional expression of glucose transporters and hexokinase-II in experimental tumor
SJ Zhao, Y Kuge, T Mochizuki, T Takahashi, K Nakada, M Sato, T Takei, N Tamaki
JOURNAL OF NUCLEAR MEDICINE, 46, 4, 675, 682, 2005年04月, ［査読有り］
英語, 研究論文（学術雑誌）

Time course of apoptotic tumor response after a single dose of chemotherapy: Comparison with 99mTc-annexin V uptake and histologic findings in an experimental model
Toshiki Takei, Yuji Kuge, Songji Zhao, Masayuki Sato, H. William Strauss, Francis G. Blankenberg, Jonathan F. Tait, Nagara Tamaki
Journal of Nuclear Medicine, 45, 12, 2083, 2087, 2004年12月01日, ［査読有り］
英語, 研究論文（学術雑誌）

Reduced oxidative metabolic response in dysfunctional myocardium with preserved glucose metabolism but with impaired contractile reserve
K Yoshinaga, C Katoh, RSB Beanlands, K Noriyasu, K Komuro, S Yamada, Y Kuge, K Morita, A Kitabatake, N Tamaki
JOURNAL OF NUCLEAR MEDICINE, 45, 11, 1885, 1891, 2004年11月, ［査読有り］
英語, 研究論文（学術雑誌）

Preparation and pharmaceutical evaluation for clinical application of high specific activity S-(-)[C-11]CGP-12177, a radioligand for beta-adrenoreceptors
K Nishijima, Y Kuge, K Seki, K Ohkura, K Morita, K Nakada, N Tamaki
NUCLEAR MEDICINE COMMUNICATIONS, 25, 8, 845, 849, 2004年08月, ［査読有り］
英語, 研究論文（学術雑誌）

Effect of steroids on [F-18]fluorodeoxyglucose uptake in an experimental tumour model
S Zhao, Y Kuge, K Nakada, T Mochizuki, T Takei, F Okada, N Tamaki
NUCLEAR MEDICINE COMMUNICATIONS, 25, 7, 727, 730, 2004年07月, ［査読有り］
英語, 研究論文（学術雑誌）

Use of a standardized uptake value for parametric in vivo imaging of benzodiazepine receptor distribution on [C-11]flumazenil brain PET
M Tsukamoto, C Katoh, T Shiga, T Kaji, Y Kuge, K Nakada, N Tamaki
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, 31, 6, 846, 851, 2004年06月, ［査読有り］
英語, 研究論文（学術雑誌）

Temporal and topographic profiles of cyclooxygenase-2 expression during 24 h of focal brain ischemia in rats
C Yokota, T Kaji, Y Kuge, H Inoue, N Tamaki, K Minematsu
NEUROSCIENCE LETTERS, 357, 3, 219, 222, 2004年03月, ［査読有り］
英語, 研究論文（学術雑誌）

Feasibility of Tc-99m-annexin V for repetitive detection of apoptotic tumor response to chemotherapy: An experimental study using a rat tumor model
Y Kuge, M Sato, SJ Zhao, T Takei, K Nakada, K Seki, HW Strauss, FG Blankenberg, JF Tait, N Tamaki
JOURNAL OF NUCLEAR MEDICINE, 45, 2, 309, 312, 2004年02月, ［査読有り］
英語, 研究論文（学術雑誌）

Characterisation of [123I]iomazenil distribution in a rat model of focal cerebral ischaemia in relation to histopathological findings
Tomohito Kaji, Yuji Kuge, Chiaki Yokota, Masafumi Tagaya, Hiroyasu Inoue, Tohru Shiga, Kazuo Minematsu, Nagara Tamaki
European Journal of Nuclear Medicine and Molecular Imaging, 31, 1, 64, 70, 1, 2004年01月, ［査読有り］
英語, 研究論文（学術雑誌）

Facile synthesis of 4a-fluoro-5,10-ethenobenzo[f]quinazolines through 1,4-photocycloaddition of 5-fluoro-1,3-dimethyluracil with substituted naphthalenes
K Ohkura, T Sugaoi, T Ishihara, K Aizawa, K Nishijima, Y Kuge, K Seki
HETEROCYCLES, 61, 377, +, 2003年12月, ［査読有り］
英語, 研究論文（学術雑誌）

Serial changes in BMIPP uptake in relation to thallium uptake in the rat myocardium after ischaemia
K Noriyasu, M Mabuchi, Y Kuge, K Morita, T Tsukamoto, T Kohya, A Kitabatake, N Tamaki
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, 30, 12, 1644, 1650, 2003年12月, ［査読有り］
英語, 研究論文（学術雑誌）

Characteristic brain distribution of 1-C-14-octanoate in a rat model of focal cerebral ischemia in comparison with those of I-123-IMP and I-123-iomazenil
Y Kuge, K Hikosaka, K Seki, K Ohkura, K Nishijima, T Kaji, S Ueno, E Tsukamoto, N Tamaki
JOURNAL OF NUCLEAR MEDICINE, 44, 7, 1168, 1175, 2003年07月, ［査読有り］
英語, 研究論文（学術雑誌）

Reduction of coronary flow reserve in areas with and without ischemia on stress perfusion imaging in patients with coronary artery disease: A study using oxygen 15-labeled water PET
K Yoshinaga, C Katoh, K Noriyasu, Y Iwado, H Furuyama, Y Ito, Y Kuge, T Kohya, A Kitabatake, N Tamaki
JOURNAL OF NUCLEAR CARDIOLOGY, 10, 3, 275, 283, 2003年05月, ［査読有り］
英語, 研究論文（学術雑誌）

Cyclooxygenase-2 expression associated with spreading depression in a primate model
C Yokota, H Inoue, Y Kuge, T Abumiya, M Tagaya, Y Hasegawa, N Ejima, N Tamaki, K Minematsu
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 23, 4, 395, 398, 2003年04月, ［査読有り］
英語, 研究論文（学術雑誌）

Dominant-negative hypoxia-inducible factor-1 alpha reduces tumorigenicity of pancreatic cancer cells through the suppression of glucose metabolism
J Chen, SJ Zhao, K Nakada, Y Kuge, N Tamaki, F Okada, JX Wang, M Shindo, F Higashino, K Takeda, M Asaka, H Katoh, T Sugiyama, M Hosokawa, M Kobayashi
AMERICAN JOURNAL OF PATHOLOGY, 162, 4, 1283, 1291, 2003年04月, ［査読有り］
英語, 研究論文（学術雑誌）

Post-ischemic cyclooxygenase-2 expression is regulated by the extent of cerebral blood flow reduction in non-human primates
C Yokota, Y Kuge, H Inoue, M Tagaya, G Kito, T Susumu, N Tamaki, K Minematsu
NEUROSCIENCE LETTERS, 341, 1, 37, 40, 2003年04月, ［査読有り］
英語, 研究論文（学術雑誌）

Estimation of myocardial blood flow and myocardial flow reserve by Tc-99m-sestamibi imaging: comparison with the results of [O-15]H2O PET
Y Ito, C Katoh, K Noriyasu, Y Kuge, H Furuyama, K Morita, T Kohya, A Kitabatake, N Tamaki
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, 30, 2, 281, 287, 2003年02月, ［査読有り］
英語, 研究論文（学術雑誌）

Altered myocardial flow reserve and endothelial function late after Kawasaki disease
H Furuyama, Y Odagawa, C Katoh, Y Iwado, Y Ito, K Noriyasu, M Mabuchi, K Yoshinaga, Y Kuge, K Kobayashi, N Tamaki
JOURNAL OF PEDIATRICS, 142, 2, 149, 154, 2003年02月, ［査読有り］
英語, 研究論文（学術雑誌）

Detection of apoptotic tumor response in vivo after a single dose of chemotherapy with Tc-99m-annexin V
T Mochizuki, Y Kuge, SJ Zhao, E Tsukamoto, M Hosokawa, HW Strauss, FG Blankenberg, JF Tait, N Tamaki
JOURNAL OF NUCLEAR MEDICINE, 44, 1, 92, 97, 2003年01月, ［査読有り］
英語, 研究論文（学術雑誌）

Accumulation of [C-11]acetate in normal prostate and benign prostatic hyperplasia: comparison with prostate cancer
T Kato, E Tsukamoto, Y Kuge, T Takei, T Shiga, N Shinohara, C Katoh, K Nakada, N Tamaki
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, 29, 11, 1492, 1495, 2002年11月, ［査読有り］
英語, 研究論文（学術雑誌）

Thermodynamically controlled photocycloaddition of 5-fluoro-1,3-dimethyluracil to naphthalenes
K Ohkura, T Sugaol, A Sakushima, K Nishijima, Y Kuge, K Seki
HETEROCYCLES, 58, 595, 600, 2002年11月, ［査読有り］
英語, 研究論文（学術雑誌）

Value and limitation of myocardial fluorodeoxyglucose single photon emission computed tomography using ultra-high energy collimators for assessing myocardial viability
M Mabuchi, N Kubo, K Morita, K Noriyasu, Y Itoh, C Katoh, Y Kuge, N Tamaki
NUCLEAR MEDICINE COMMUNICATIONS, 23, 9, 879, 885, 2002年09月, ［査読有り］
英語, 研究論文（学術雑誌）

Decreased endothelium-dependent coronary vasomotion in healthy young smokers
Y Iwado, K Yoshinaga, H Furuyama, Y Ito, K Noriyasu, C Katoh, Y Kuge, E Tsukamoto, N Tamaki
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, 29, 8, 984, 990, 2002年08月, ［査読有り］
英語, 研究論文（学術雑誌）

Clinical role of F-18-FDG PET for initial staging of patients with extrahepatic bile duct cancer
T Kato, E Tsukamoto, Y Kuge, C Katoh, T Nambu, A Nobuta, S Kondo, M Asaka, N Tamaki
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, 29, 8, 1047, 1054, 2002年08月, ［査読有り］
英語, 研究論文（学術雑誌）

Increased [F-18]2-fluoro-2-deoxy-D-glucose ([F-18]FDG) yield with recycled target [O-18]water: factors affecting the [F-18]FDG yield
K Nishijima, Y Kuge, E Tsukamoto, K Seki, K Ohkura, Y Magata, A Tanaka, K Nagatsu, N Tamaki
APPLIED RADIATION AND ISOTOPES, 57, 1, 43, 49, 2002年07月, ［査読有り］
英語, 研究論文（学術雑誌）

Low-dose dobutamine stress gated SPET for identification of viable myocardium: comparison with stress-rest perfusion SPET and PET
K Yoshinaga, C Katoh, K Noriyasu, S Yamada, Y Ito, Y Kuge, Y Kawai, T Kohya, A Kitabatake, N Tamaki
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, 29, 7, 882, 890, 2002年07月, ［査読有り］
英語, 研究論文（学術雑誌）

Unique profile of spreading depression in a primate model
C Yokota, Y Kuge, Y Hasegawa, M Tagaya, T Abumiya, N Ejima, N Tamaki, T Yamaguchi, K Minematsu
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 22, 7, 835, 842, 2002年07月, ［査読有り］
英語, 研究論文（学術雑誌）

Fluorodeoxyglucose uptake and glucose transporter expression in experimental inflammatory lesions and malignant tumours: effects of insulin and glucose loading
S Zhao, Y Kuge, E Tsukamoto, T Mochizuki, T Kato, K Hikosaka, K Nakada, M Hosokawa, M Kohanawa, N Tamaki
NUCLEAR MEDICINE COMMUNICATIONS, 23, 6, 545, 550, 2002年06月, ［査読有り］
英語, 研究論文（学術雑誌）

Assessment of coronary function in children with a history of Kawasaki disease using O-15-water positron emission tomography
H Furuyama, Y Odagawa, C Katoh, Y Iwado, K Yoshinaga, Y Ito, K Noriyasu, M Mabuchi, Y Kuge, K Kobayashi, N Tamaki
CIRCULATION, 105, 24, 2878, 2884, 2002年06月, ［査読有り］
英語, 研究論文（学術雑誌）

Intense F-18FDG accumulation in the stomach in a patient with Menetrier's disease
T Kato, Y Komatsu, E Tsukamoto, M Takei, T Takei, F Yamamoto, Y Kuge, M Asaka, N Tamaki
CLINICAL NUCLEAR MEDICINE, 27, 5, 376, 377, 2002年05月, ［査読有り］
英語

Quantitative evaluation of the relative contribution ratio of cerebral tissue to near-infrared signals in the adult human head: a preliminary study
S Kohri, Y Hoshi, M Tamura, C Kato, Y Kuge, N Tamaki
PHYSIOLOGICAL MEASUREMENT, 23, 2, 301, 312, 2002年05月, ［査読有り］
英語, 研究論文（学術雑誌）

Stereoselective synthesis of 4a-fluoro-5,10-ethenobenzo[f]quinazolines via photo-Diels-Alder reaction of 5-fluoro-1,3-dimethyluracil with naphthalenes
K Ohkura, T Sugaoi, K Nishijima, Y Kuge, K Seki
TETRAHEDRON LETTERS, 43, 17, 3113, 3115, 2002年04月, ［査読有り］
英語, 研究論文（学術雑誌）

A simplified and improved synthesis of [C-11]phosgene with iron and iron (III) oxide
KI Nishijima, Y Kuge, K Seki, K Ohkura, N Motoki, K Nagatsu, A Tanaka, E Tsukamoto, N Tamaki
NUCLEAR MEDICINE AND BIOLOGY, 29, 3, 345, 350, 2002年04月, ［査読有り］
英語, 研究論文（学術雑誌）

In vitro uptake of [1-C-14]Octanoate in brain slices of rats: basic studies for assessing [1-(11C)]Octanoate as a PET tracer of glial functions
Y Kuge, K Hikosaka, K Seki, K Ohkura, K Nishijima, E Tsukamoto, N Tamaki
NUCLEAR MEDICINE AND BIOLOGY, 29, 3, 303, 306, 2002年04月, ［査読有り］
英語, 研究論文（学術雑誌）

Chemical impurities in [F-18]FDG preparations produced by solid-phase F-18-fluorination
Y Kuge, K Nishijima, K Nagatsu, K Seki, K Ohkura, A Tanaka, M Sasaki, E Tsukamoto, N Tamaki
NUCLEAR MEDICINE AND BIOLOGY, 29, 2, 275, 279, 2002年02月, ［査読有り］
英語, 研究論文（学術雑誌）

Low-dose dobutamine stress gated SPET for identification of viable myocardium: Comparison with stress-rest perfusion SPET and PET
Keiichiro Yoshinaga, Chietsugu Katoh, Kazuyuki Noriyasu, Satoshi Yamada, Yoshinori Ito, Yuji Kuge, Yuko Kawai, Tetsuro Kohya, Akira Kitabatake, Nagara Tamaki
European Journal of Nuclear Medicine, 29, 7, 882, 890, 2002年, ［査読有り］
英語, 研究論文（学術雑誌）

Clinical role of 18F-FDG PET for initial staging of patients with extrahepatic bile duct cancer
Takashi Kato, Eriko Tsukamoto, Yuji Kuge, Chietsugu Katoh, Toshikazu Nambu, Aichiro Nobuta, Satoshi Kondo, Masahiro Asaka, Nagara Tamaki
European Journal of Nuclear Medicine, 29, 8, 1047, 1054, 2002年, ［査読有り］
英語, 研究論文（学術雑誌）

Decreased endothelium-dependent coronary vasomotion in healthy young smokers
Yasuyoshi Iwado, Keiichiro Yoshinaga, Hideto Furuyama, Yoshinori Ito, Kazuyuki Noriyasu, Chietsugu Katoh, Yuji Kuge, Eriko Tsukamoto, Nagara Tamaki
European Journal of Nuclear Medicine, 29, 8, 984, 990, 2002年, ［査読有り］
英語, 研究論文（学術雑誌）

Accumulation of [11C]acetate in normal prostate and benign prostatic hyperplasia: Comparison with prostate cancer
Takashi Kato, Eriko Tsukamoto, Yuji Kuge, Toshiki Takei, Tohru Shiga, Nobuo Shinohara, Chietsugu Katoh, Kunihiro Nakada, Nagara Tamaki
European Journal of Nuclear Medicine, 29, 11, 1492, 1495, 2002年, ［査読有り］
英語, 研究論文（学術雑誌）

Synthesis of 9,11-diazapentacyclo[6.4.0.0(1,3).0(2,5).0(4,8)]dodecane-2,4-diones
K Ohkura, K Nishijima, Y Kuge, K Seki
HETEROCYCLES, 56, 1-2, 235, 244, 2002年01月, ［査読有り］
英語, 研究論文（学術雑誌）

FDG uptake and glucose transporter subtype expressions in experimental tumor and inflammation models
TA Mochizuki, E Tsukamoto, Y Kuge, K Kanegae, SJ Zhao, K Hikosaka, M Hosokawa, M Kohanawa, N Tamaki
JOURNAL OF NUCLEAR MEDICINE, 42, 10, 1551, 1555, 2001年10月, ［査読有り］
英語, 研究論文（学術雑誌）

Low-dose dobutamine electrocardiograph-gated myocardial SPECT for identifying viable myocardium: Comparison with dobutamine stress echocardiography and PET
K Yoshinaga, K Morita, S Yamada, K Komuro, C Katoh, Y Ito, Y Kuge, T Kohya, A Kitabatake, N Tamaki
JOURNAL OF NUCLEAR MEDICINE, 42, 6, 838, 844, 2001年06月, ［査読有り］
英語, 研究論文（学術雑誌）

Effects of insulin and glucose loading on FDG uptake in experimental malignant tumours and inflammatory lesions
S Zhao, Y Kuge, E Tsukamoto, T Mochizuki, T Kato, K Hikosaka, M Hosokawa, M Kohanawa, N Tamaki
EUROPEAN JOURNAL OF NUCLEAR MEDICINE, 28, 6, 730, 735, 2001年06月, ［査読有り］
英語, 研究論文（学術雑誌）

オンカラム法(FDG MicroLabTM)を用いる18F-FDGの合成 エンドトキシン試験及び無菌試験に関する検討
久下 裕司, 西嶋 剣一, 永津 弘太郎, 田中 明, 塚本 江利子, 玉木 長良
核医学, 38, 2, 125, 130, (一社)日本核医学会, 2001年03月, ［査読有り］
日本語

Comparison of F-18-FDG, I-131-Na, and Tl-201 in diagnosis of recurrent or metastatic thyroid carcinoma
T Shiga, E Tsukamoto, K Nakada, K Morita, T Kato, M Mabuchi, K Yoshinaga, C Katoh, Y Kuge, N Tamaki
JOURNAL OF NUCLEAR MEDICINE, 42, 3, 414, 419, 2001年03月, ［査読有り］
英語, 研究論文（学術雑誌）

Serial changes in cerebral blood flow and flow-metabolism uncoupling in primates with acute thromboembolic stroke
Y Kuge, C Yokota, M Tagaya, Y Hasegawa, A Nishimura, G Kito, N Tamaki, N Hashimoto, T Yamaguchi, K Minematsu
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 21, 3, 202, 210, 2001年03月, ［査読有り］
英語, 研究論文（学術雑誌）

Performance assessment of O-18 water purifier
H Kitano, Y Magata, A Tanaka, T Mukai, Y Kuge, K Nagatsu, J Konishi, H Saji
ANNALS OF NUCLEAR MEDICINE, 15, 1, 75, 78, 2001年02月, ［査読有り］
英語, 研究論文（学術雑誌）

Experimental thromboembolic stroke in cynomolgus monkey
G Kito, A Nishimura, T Susumu, R Nagata, Y Kuge, C Yokota, K Minematsu
JOURNAL OF NEUROSCIENCE METHODS, 105, 1, 45, 53, 2001年01月, ［査読有り］
英語, 研究論文（学術雑誌）

Biodistribution of 3,4-dihydro-5-[C-11]methoxy-1(2H)-isoquinolinone, a potential PET tracer for poly(ADP-ribose) synthetase
Y Miyake, Y Kuge, H Shimadzu, N Hashimoto, Y Ishida, M Shibakawa, T Nishimura
NUCLEAR MEDICINE AND BIOLOGY, 27, 8, 701, 705, 2000年11月, ［査読有り］
英語, 研究論文（学術雑誌）

[1-C-11]Octanoate as a PET tracer for studying ischemic stroke: Evaluation in a canine model of thromboembolic stroke with positron emission tomography
Y Kuge, H Kawashima, K Minematsu, Y Hasegawa, T Yamaguchi, Y Miyake, T Hashimoto, M Imanishi, M Shiomi, N Tamaki, N Hashimoto
BIOLOGICAL & PHARMACEUTICAL BULLETIN, 23, 8, 984, 988, 2000年08月, ［査読有り］
英語, 研究論文（学術雑誌）

Effects of single and repetitive spreading depression on cerebral blood flow and glucose metabolism in cats: a PET study
Y Kuge, Y Hasegawa, C Yokota, K Minematsu, N Hashimoto, Y Miyake, T Yamaguchi
JOURNAL OF THE NEUROLOGICAL SCIENCES, 176, 2, 114, 123, 2000年06月, ［査読有り］
英語, 研究論文（学術雑誌）

Preliminary evaluation of [1-C-11]octanoate as a PET tracer for studying cerebral ischemia: A PET study in rat and canine models of focal cerebral ischemia
Y Kuge, H Kawashima, T Hashimoto, M Imanishi, M Shiomi, K Minematsu, Y Hasegawa, T Yamaguchi, Y Miyake, N Hashimoto
ANNALS OF NUCLEAR MEDICINE, 14, 1, 69, 74, 2000年02月, ［査読有り］
英語, 研究論文（学術雑誌）

FDG MicroLabTMシステムを用いる18F-FDGの合成：臨床応用のための基礎的検討　　　　　　　　　　　　　　　
久下裕司, 塚本江利子, 加藤千恵次, 関興一, 大倉一枝, 大宮康明, 西嶋剣一, 田中明, 佐々木基仁, 玉木長良
核医学, 36, 873, 878, 1999年, ［査読有り］

全身FDG 検査における正常分布の検討　　　　　　　　　　　　　　　
加藤貴司, 塚本江利子, 杉並裕子, 高野晶寛, 馬淵恵, 吉永恵一郎, 志賀哲, 森田浩一, 加藤千恵次, 足立至, 久下裕司, 玉木長良
核医学, 36, 971, 977, 1999年, ［査読有り］

Development of step-specific PET tracers for studying fatty acid beta-oxidation: Biodistribution of [1-C-11] octanoate analogs in rats and a cat
H Kawashima, Y Kuge, K Yajima, Y Miyake, N Hashimoto
NUCLEAR MEDICINE AND BIOLOGY, 25, 6, 543, 548, 1998年08月, ［査読有り］
英語, 研究論文（学術雑誌）

脳核医学診断用自動ROI設定システムの動物PET実験への応用　　　　　　　　　　　　　　　
久下裕司, 赤井信夫, 田村浩司, 山田学, 谷崎直昭, 橋本忠俊, 今西三明, 塩見美江, 石田良雄, 橋本直人
核医学, 35, 733, 740, 1998年, ［査読有り］

Synthesis of [1-C-11]-2-octynoic acid, [1-C-11]-2-decynoic acid and [1-C-11]-3-(R,S)-methylocatanoic acid as potential markers for PET studies of fatty acid metabolism
H Kawashima, K Yajima, Y Kuge, N Hashimoto, Y Miyake
JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS, 39, 3, 181, 193, 1997年03月, ［査読有り］
英語, 研究論文（学術雑誌）

Positron emission tomography for quantitative determination of glucose metabolism in normal and ischemic brains in rats: An insoluble problem by the Harderian glands
Y Kuge, K Minematsu, Y Hasegawa, T Yamaguchi, H Mori, H Matsuura, N Hashimoto, Y Miyake
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 17, 1, 116, 120, 1997年01月, ［査読有り］
英語, 研究論文（学術雑誌）

[1-11C]octanoate as a potential PET tracer for studying glial functions: PET evaluation in rats and cats
Yuji Kuge, Hidefumi Kawashima, Shunji Yamazaki, Naoto Hashimoto, Yoshihiro Miyake
Nuclear Medicine and Biology, 23, 8, 1009, 1012, 1996年11月, ［査読有り］
英語, 研究論文（学術雑誌）

[1-C-11]octanoate as a potential PET tracer for studying glial functions: PET evaluation in rats and cats
Y Kuge, H Kawashima, S Yamazaki, N Hashimoto, Y Miyake
NUCLEAR MEDICINE AND BIOLOGY, 23, 8, 1009, 1012, 1996年11月, ［査読有り］
英語, 研究論文（学術雑誌）

Uptake of radioactive octanoate in astrocytoma cells: Basic studies for application of [11C]octanoate as a PET tracer
Shunji Yamazaki, Kiyoshi Fukui, Hidefumi Kawashima, Yuji Kuge, Yoshihiro Miyake, Kenji Kangawa
Annals of Nuclear Medicine, 10, 4, 395, 399, Springer Tokyo, 1996年, ［査読有り］
英語, 研究論文（学術雑誌）

NYLON MONOFILAMENT FOR INTRALUMINAL MIDDLE CEREBRAL-ARTERY OCCLUSION IN RATS
Y KUGE, K MINEMATSU, T YAMAGUCHI, Y MIYAKE
STROKE, 26, 9, 1655, 1657, 1995年09月, ［査読有り］
英語, 研究論文（学術雑誌）

Brain uptake and metabolism of [1-11C]octanoate in rats: Pharmacokinetic basis for its application as a radiopharmaceutical for studying brain fatty acid metabolism
Yuji Kuge, Kazuyoshi Yajima, Hidefumi Kawashima, Hiroyoshi Yamazaki, Naoto Hashimoto, Yoshihiro Miyake
Annals of Nuclear Medicine, 9, 3, 137, 142, 1995年09月, ［査読有り］
英語, 研究論文（学術雑誌）

OPTIMAL FORMULATION OF AN ANGIOGENESIS INHIBITOR, TNP-470, FOR ARTERIAL INJECTION DETERMINED BY IN-VITRO DRUG-RELEASE AND STABILITY, AND IN-VIVO ANTITUMOR-ACTIVITY
S YANAI, H OKADA, K SAITO, Y KUGE, Y OGAWA, H TOGUCHI
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 123, 2, 237, 245, 1995年09月, ［査読有り］
英語, 研究論文（学術雑誌）

ANTITUMOR EFFECT OF ARTERIAL ADMINISTRATION OF A MEDIUM-CHAIN TRIGLYCERIDE SOLUTION OF AN ANGIOGENESIS INHIBITOR, TNP-470, IN RABBITS BEARING VX-2 CARCINOMA
S YANAI, H OKADA, K SAITO, Y KUGE, M MISAKI, Y OGAWA, H TOGUCHI
PHARMACEUTICAL RESEARCH, 12, 5, 653, 657, 1995年05月, ［査読有り］
英語, 研究論文（学術雑誌）

ANTITUMOR-ACTIVITY OF A MEDIUM-CHAIN TRIGLYCERIDE SOLUTION OF THE ANGIOGENESIS INHIBITOR TNP-470 (AGM-1470) WHEN ADMINISTERED VIA THE HEPATIC-ARTERY TO RATS BEARING WALKER-256 CARCINOSARCOMA IN THE LIVER
S YANAI, H OKADA, M MISAKI, K SAITO, Y KUGE, Y OGAWA, H TOGUCHI
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 271, 3, 1267, 1273, 1994年12月, ［査読有り］
英語, 研究論文（学術雑誌）

ACCUMULATION OF RADIOACTIVITY IN THE PANCREAS AFTER INTRAVENOUS ADMINISTRATION OF [N-13] AMMONIA
H SAJI, Y KUGE, K YAMAMOTO, Y MAGATA, Y YONEKURA, J KONISHI, A YOKOYAMA
NUCLEAR MEDICINE AND BIOLOGY, 19, 5, 531, &, 1992年07月, ［査読有り］
英語, 研究論文（学術雑誌）

INVESTIGATION OF RADIOPHARMACEUTICALS FOR PANCREATIC IMAGING - ACCUMULATION OF AMINES IN THE PANCREAS
H SAJI, Y KUGE, Y MAGATA, Y FUJIBAYASHI, A YOKOYAMA
CHEMICAL & PHARMACEUTICAL BULLETIN, 40, 1, 161, 164, 1992年01月, ［査読有り］
英語, 研究論文（学術雑誌）

Accumulation and metabolism of [125I] HIPDM in the rat pancreas
Hideo Saji, Yuji Kuge, Daisuke Tsutsumi, Kazutaka Yamamoto, Junji Konishi, Akira Yokoyama
Annals of Nuclear Medicine, 5, 4, 157, 161, 1991年12月, ［査読有り］
英語, 研究論文（学術雑誌）

新規カルシウム拮抗薬 Manidipine Hydrochloride [CV-4093(2HCl)]のラット、イヌにおける代謝　　　　　　　　　　　　　　　
吉田清志, 三谷政義, 塚本剛司, 久下裕司, 小林卓郎, 棚山薫晴
薬理と治療, 17, 2119, 2135, 1989年

遺伝子組換え型ヒトインターロイキン-2 (TGP-3) のラット、マウス、ウサギ、イヌ、サルにおける薬物動態　　　　　　　　　　　　　　　
小林卓郎, 久下裕司, 朴木英明, 飯沢祐史, 山本仁, 石古博昭, 棚山薫晴
基礎と臨床, 23, 4309, 4325, 1989年

INVIVO EVALUATION OF RADIOIODINATED SPIROPERIDOL DERIVATIVES AS RADIOPHARMACEUTICAL FOR DOPAMINE RECEPTOR STUDY
H SAJI, T TOKUI, A SAIGA, Y KUGE, NAKATSUKA, I, M OKUNO, A YOSHITAKE, K TORIZUKA, A YOKOYAMA
JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS, 23, 10-12, 1323, 1324, 1986年10月, ［査読有り］
英語

PSMA-PET ～PETによる最新の前立腺癌診断法～　　　　　　　　　　　　　　　
久下裕司, 志賀 哲, 水野雄貴, 平田健司, Isotope News, 774, 18, 21, 2021年04月
記事・総説・解説・論説等（学術雑誌）

Clinical practice guidelines for high-resolution breast PET, 2019 edition
Yoko Satoh, Masami Kawamoto, Kazunori Kubota, Koji Murakami, Makoto Hosono, Michio Senda, Masayuki Sasaki, Toshimitsu Momose, Kengo Ito, Terue Okamura, Keiichi Oda, Yuji Kuge, Minoru Sakurai, Ukihide Tateishi, Yasuhisa Fujibayashi, Yasuhiro Magata, Takeshi Yoshida, Atsuo Waki, Katsuhiko Kato, Teisuke Hashimoto, Mayuki Uchiyama, Seigo Kinuya, Tatsuya Higashi, Yasuhiro Magata, Akihiro Machitori, Hirotaka Maruno, Ryogo Minamimoto, Keiichiro Yoshinaga, Annals of Nuclear Medicine, 35, 3, 406, 414, 2021年03月, ［査読有り］, ［招待有り］, ［国内誌］
Breast positron emission tomography (PET) has had insurance coverage when performed with conventional whole-body PET in Japan since 2013. Together with whole-body PET, accurate examination of breast cancer and diagnosis of metastatic disease are possible, and are expected to contribute significantly to its treatment planning. To facilitate a safer, smoother, and more appropriate examination, the Japanese Society of Nuclear Medicine published the first edition of practice guidelines for high-resolution breast PET in 2013. Subsequently, new types of breast PET have been developed and their clinical usefulness clarified. Therefore, the guidelines for breast PET were revised in 2019. This article updates readers as to what is new in the second edition. This edition supports two different types of breast PET depending on the placement of the detector: the opposite-type (positron emission mammography; PEM) and the ring-shaped type (dedicated breast PET; dbPET), providing an overview of these scanners and appropriate imaging methods, their clinical applications, and future prospects. The name “dedicated breast PET” from the first edition is widely used to refer to ring-shaped type breast PET. In this edition, “breast PET” has been defined as a term that refers to both opposite- and ring-shaped devices. Up-to-date breast PET practice guidelines would help provide useful information for evidence-based breast imaging., Springer Science and Business Media LLC, 英語

光免疫療法による腫瘍環境の変化に関する［18F］FDG と［18F］FMISO を用いた検討　　　　　　　　　　　　　　　
中島孝平, 杉川晃代, 安井 博宣, 東川桂, 高倉栄男, 志賀哲, 久下裕司, 小川美香子, 日本分子イメージング学会誌 JSMI Report, 13, 1, 17, 22, 2020年01月, ［査読有り］, ［招待有り］
日本語, 記事・総説・解説・論説等（国際会議プロシーディングズ）

The Roles of Hypoxia Imaging Using 18F-Fluoromisonidazole Positron Emission Tomography in Glioma Treatment.
Kenji Hirata, Shigeru Yamaguchi, Tohru Shiga, Yuji Kuge, Nagara Tamaki, Journal of clinical medicine, 8, 8, E1088, 2019年07月24日, ［査読有り］, ［招待有り］, ［国際誌］
Glioma is the most common malignant brain tumor. Hypoxia is closely related to the malignancy of gliomas, and positron emission tomography (PET) can noninvasively visualize the degree and the expansion of hypoxia. Currently, 18F-fluoromisonidazole (FMISO) is the most common radiotracer for hypoxia imaging. The clinical usefulness of FMISO PET has been established; it can distinguish glioblastomas from lower-grade gliomas and can predict the microenvironment of a tumor, including necrosis, vascularization, and permeability. FMISO PET provides prognostic information, including survival and treatment response information. Because hypoxia decreases a tumor's sensitivity to radiation therapy, dose escalation to an FMISO-positive volume is an attractive strategy. Although this idea is not new, an insufficient amount of evidence has been obtained regarding this concept. New tracers for hypoxia imaging such as 18F-DiFA are being tested. In the future, hypoxia imaging will play an important role in glioma management., 英語

放射性医薬品の取扱に関するアンケート調査報告。　　　　　　　　　　　　　　　
日本核医学会, 核医学領域における薬剤師の在り方検討委員会, 久下裕司, 桒原健, 小泉潔, 鈴木貴明, 藤塚一行, 間賀田泰寛, 八島秀明, 放射性医薬品取り扱いガイドライン講習会ワーキンググループ委員, 荒野泰, 岡沢秀彦, 小川清, 小野欽也, 片渕哲朗, 川井恵一, 倉橋達人, 小池克美, 小泉潔, 中川貴之, 藤塚一行, 間賀田泰寛, 核医学, 56, 25, 31, 2019年

Imaging modalities for drug-related osteonecrosis of the jaw (3), Positron emission tomography imaging for the diagnosis of medication-related osteonecrosis of the jaw.
Kitagawa Y, Ohga N, Asaka T, Sato J, Hata H, Helman J, Tsuboi K, Amizuka N, Kuge Y, Shiga T, Jpn Dent Sci Rev., 55, 1, 65, 67, 2019年, ［招待有り］, ［国際誌］
Medication-related osteonecrosis of jaws (MRONJ) is one of the most complicated inflammatory conditions in oral and maxillofacial region. It is very difficult to correctly evaluate the degree and extent of necrosis and infection. This refractory osteonecrosis often needs extended surgery, leading to impaired quality-of-life. We have performed hyperbaric oxygen therapy (HBO) combined with conservative surgery for advanced cases. We have appraised the value of FDG-PET and 3-phase bone scintigraphy in the diagnosis and management of this condition. MRONJ showed significantly higher SUVmax on FDG-PET than the others. Although the 3 phase pool bone images did not change significantly, perfusion and static bone image as well as PET showed remarkable response to HBO for MRONJ. SUVmax after HBO was significantly lower than those of before HBO. These preliminary results indicate that FDG-PET is useful for monitoring the effect of HBO for MRONJ., 英語

FDG PET、PET/CT診療ガイドライン2018
細野 眞, 千田 道雄, 佐々木 雅之, 百瀬 敏光, 伊藤 健吾, 岡村 光英, 織田 圭一, 川本 雅美, 久下 裕司, 櫻井 実, 立石 宇貴秀, 藤林 康久, 間賀田 泰寛, 村上 康二, 吉田 毅, 脇 厚生, 加藤 克彦, 橋本 禎介, 内山 眞幸, 絹谷 清剛, 東 達也, 待鳥 詔洋, 丸野 廣大, 南本 亮吾, 吉永 恵一郎, 日本核医学会, PET核医学委員会, 健保委員会, 核医学, 55, 1, 1, 22, 2018年12月
(一社)日本核医学会, 日本語

Nuclear Medicine Today 2018 最新トピックスから探る核医学の現在と未来 ?Theranosticsに向けた研究開発の最新トピックス 5．68Ge/68Gaジェネレータを用いるPET薬剤の研究開発と将来展望。　　　　　　　　　　　　　　　
久下裕司, 東川 桂, 岡本祥三, 志賀 哲, INNERVISION, 33, 11, 58, 61, 2018年, ［招待有り］
日本語

Nuclear Medicine Today 2018 最新トピックスから探る核医学の現在と未来 ?Theranosticsに向けた研究開発の最新トピックス 4．前立腺がんに対するPSMA-PETとPSMAによるアイソトープ治療の最新動向。　　　　　　　　　　　　　　　
岡本祥三, 志賀 哲, 久下裕司, INNERVISION, 33, 11, 55, 57, 2018年, ［招待有り］
日本語

口腔癌における低酸素分子イメージング　　　　　　　　　　　　　　　
北川善政, 佐藤 淳, 大賀則孝, 浅香卓哉, 竹内康人, 犬伏正幸, 久下裕司, 志賀 哲, お茶の水醫學雑誌, 66, 2, 193, 211, 2018年, ［招待有り］
お茶の水医学会, 日本語

特集 薬剤関連顎骨壊死の画像診断up to date。 薬剤関連顎骨壊死のPET検査。　　　　　　　　　　　　　　　
北川 善政, 浅香 卓哉, 佐藤 淳, 秦 浩信, 坪井 香奈子, 網塚 憲生, 久下 裕司, 志賀 哲, 臨床放射線, 63, 10, 1071, 1081, 2018年, ［招待有り］
日本語

Recent Advances in the Development of PET/SPECT Probes for Atherosclerosis Imaging
Yoichi Shimizu, Yuji Kuge, Nuclear Medicine and Molecular Imaging, 50, 4, 284, 291, 2016年12月01日, ［査読有り］, ［招待有り］
Springer Verlag, 英語, 書評論文,書評,文献紹介等

イメージングによる“がん”の治療効果予測−新規核医学診断薬（[123I]IIMU）の臨床研究への歩み−　　　　　　　　　　　　　　　
久下裕司, 西嶋剣一, 大倉一枝, 志賀 哲, 玉木長良, ISOTOPE NEWS, 729, 16, 20, 2015年, ［招待有り］
日本語

新しいがんの放射線生物学を拓くイメージング技術
安井 博宣, 戒田 篤志, 兵藤 文紀, 三浦 大典, 久下 裕司, 松本 孔貴, 放射線生物研究, 49, 3, 263, 283, 2014年09月, ［招待有り］
放射線生物研究会, 日本語

放射線施設の建替えに関する構想について
野矢 洋一, 阿保 憲史, 志水 陽一, 久保 直樹, 久下 裕司, 日本放射線安全管理学会誌, 13, 1, 51, 54, 2014年, ［招待有り］
In this report, we introduced our project of the extension and the rebuilding of the building of Central Institute of Isotope Science (CIS), Hokkaido University, which has been planned in terms of the present state and the future outlook for the management of CIS. We first fixed a layout of that building and the dose of radioisotope (RI) in the renewed CIS building in consideration of the present usage states, and then carried out a sort of designing of building such as calculation of the wall thickness corresponded to the RI usage dose, arrangement of exhaust and drainage equipments, and so on. Furthermore, we attempted to design the building with an appropriate function for education and safety control of radiation and RI as well as flexibility in response to user's demands on performing a various kind of researches., Japanese Society of Radiation Safety Management, 日本語

イメージング質量分析を用いたスフィンゴミエリンの組織内分布と制御機構の解明　　　　　　　　　　　　　　　
杉本正志, 志水陽一, 五十嵐靖之, 久下裕司, JSMI Report, 9, 1, 43, 45, 2014年, ［招待有り］
日本語

核医学による代謝の空間的，定量的評価
久下裕司, 血栓止血誌, 25, 3, 363, 370, 2014年, ［招待有り］
日本語

Molecular Imaging 2014 分子イメージングはどこまで進んだか ?分子イメージングの最新動向 １．核医学における分子イメージングの最新動向 5)製造標準化の現状と展望　　　　　　　　　　　　　　　
脇厚生, 久下裕司, 西嶋剣一, 藤林靖久, INNERVISION, 29, 7, 23, 26, 2014年, ［招待有り］
日本語

核医学診断の新しい展開 : がん治療戦略への応用
久下 裕司, 趙 松吉, 志賀 哲, 放射線生物研究, 48, 4, 353, 363, 2013年12月
放射線生物研究会, 日本語

特集 心臓病における核医学検査の進歩 循環器領域の放射性薬剤の進歩
久下裕司, 呼吸と循環, 61, 11, 1001, 1007, 2013年, ［招待有り］
日本語

特集 心血管イメージング最前線−エコー, CTからcoronary imagingまで−５．核医学検査 f. 分子イメージングの方向性　　　　　　　　　　　　　　　
久下裕司, 玉木長良, Heart View, 17, 12(増刊号), 320, 325, 2013年, ［招待有り］
日本語

特集 「百聞は一見にしかず 生体イメージングがもたらす診断と治療の戦略」セミナー 循環器領域の分子イメージング　　　　　　　　　　　　　　　
久下裕司, 玉木長良, ファルマシア, 49, 7, 682, 687, 2013年, ［招待有り］
日本語

特集 不安定プラークの病態と診断 10.不安定プラークと分子イメージング　　　　　　　　　　　　　　　
久下裕司, 玉木長良, 月刊循環器, 3, 1, 69, 77, 2013年, ［招待有り］
日本語

Molecular imaging in heart failure patients　　　　　　　　　　　　　　　
Tamaki N, Kuge Y, Yoshinaga K, Clin Transl Imaging, 1, 5, 341, 354, 2013年, ［招待有り］
英語

骨髄間質細胞移植は脳梗塞後の局所糖代謝を改善する : 小動物用PET/CTによる検討
宮本 倫行, 黒田 敏, 趙 松吉, 孫田 恵一, 伊東 雅基, 川堀 真人, 七戸 秀夫, 宝金 清博, 久下 裕司, 玉木 長良, 北海道醫學雜誌 = Acta medica Hokkaidonensia, 87, 6, 269, 269, 2012年11月01日
日本語

特集１ 心臓核医学の最先端 1．動脈硬化イメージング−実験的検討　　　　　　　　　　　　　　　
久下裕司, 趙 芫, 趙 松吉, 玉木長良, ＰＥＴジャーナル, 18, 14, 16, 2012年, ［招待有り］
日本語

医薬品開発（又は創薬・育薬）における分子イメージング技術の現状と進歩　　　　　　　　　　　　　　　
久下裕司, 西嶋剣一, 孫田恵一, 趙 松吉, 玉木長良, 医薬品医療機器レギュラトリーサイエンス, 43, 4, 308, 313, 2012年, ［招待有り］
日本語

交感神経と循環器疾患 交感神経イメージング　　　　　　　　　　　　　　　
玉木長良, 吉永恵一郎, 久下裕司, Cardiac Practice, 23, 2, 143, 147, 2012年, ［招待有り］
日本語

特集 冠動脈疾患の診断・治療における画像診断の進歩 分子イメージングによる冠動脈病変評価　　　　　　　　　　　　　　　
玉木長良, 吉永恵一郎, 久下裕司, Cardiac Practice, 23, 1, 23, 27, 2012年, ［招待有り］
日本語

動脈硬化プラーク評価における分子イメージングの有用性と展望 (特集 MDCT・MRI・SPECT・PETをいかに使い分けるか) -- (CTによる冠動脈狭窄評価能--最新のエビデンスと臨床適応)
玉木 長良, 久下 裕司, 心CT, 35, 40, 2011年03月
文光堂, 日本語

特集１ 次世代腫瘍分子イメージング ４．アポトーシスイメージングプローブ　　　　　　　　　　　　　　　
久下裕司, 竹井俊樹, 趙 松吉, ＰＥＴジャーナル, 13, 23, 25, 2011年, ［招待有り］
日本語

特集１ 核医学検査の新しい展開〜治療戦略への応用 治療戦略に役立つ放射性薬剤の開発　　　　　　　　　　　　　　　
久下裕司, 西嶋剣一, 趙 松吉, 映像情報メディカル, 43, 11, 842, 849, 2011年, ［招待有り］
日本語

心不全の分子イメージング　　　　　　　　　　　　　　　
玉木長良, 吉永恵一郎, 久下裕司, 日本心不全学会 News Letter, 15, 2, 8, 9, 2011年, ［招待有り］
日本語

SPECT、PETによるプラークイメージング　　　　　　　　　　　　　　　
玉木長良, 趙 芫, 久下裕司, 動脈硬化予防, 9, 2, 53, 57, 2010年, ［招待有り］
日本語

Molecular Imaging of Apoptosis with Radio-Labeled Annexin A5 Focused on the Evaluation of Tumor Response to Chemotherapy
Yuji Kuge, Songji Zhao, Toshiki Takei, Nagara Tamaki, ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY, 9, 9, 1003, 1011, 2009年11月, ［査読有り］, ［招待有り］
英語

PET核医学検査による評価　　　　　　　　　　　　　　　
玉木長良, 趙 芫, 久下裕司, 志賀哲, Mebio, 26, 4, 114, 118, 2009年, ［招待有り］
日本語

核医学の軌跡(PETを中心に)　　　　　　　　　　　　　　　
玉木長良, 吉永恵一郎, 久下裕司, DIGITALMEDICINE, 42, 26, 29, 2009年, ［招待有り］
日本語

Myocardial metabolic imaging in the clinical setting　　　　　　　　　　　　　　　
Tamaki N, Kuge Y, Yoshinaga K, Eur Cardiolgy, 5, 1, 15, 18, 2009年, ［招待有り］
英語

放射線治療を指向したPET/SPECTプローブの開発〜低酸素イメージングを中心に〜　　　　　　　　　　　　　　　
久下裕司, 上田真史, 趙 松吉, 工藤 喬, 近藤科江, 田中正太郎, 玉木長良, 平岡眞寛, 佐治英郎, 癌の臨床, 54, 2, 105, 108, 2008年, ［招待有り］
日本語

分子イメージングとがん治療戦略：イメージングによるインビボ組織染色を目指して　　　　　　　　　　　　　　　
久下裕司, 佐治英郎, 玉木長良, 趙松吉, 関興一, 上田真史, 清野泰, INNERVISION, 22, 7, 42, 2007年, ［招待有り］
日本語

心受容体イメージング　　　　　　　　　　　　　　　
玉木長良, 塚本隆裕, 犬伏正幸, 久下裕司, 日本臨床, 65, 2, 303, 307, 2007年, ［招待有り］
日本語

PETの展望 「新しいPET用薬剤」　　　　　　　　　　　　　　　
久下裕司, 西嶋剣一, Pharma Medica, 24, 10, 51, 54, 2006年, ［招待有り］
日本語

動脈硬化病態の解析と分子イメージング：プロスタグランジン合成酵素を標的として　　　　　　　　　　　　　　　
久下裕司, 佐治英郎, 清野泰, 横田千晶, 玉木長良, 関興一, INNERVISION, 21, 7, 17, 2006年, ［招待有り］
日本語

動脈硬化の質的診断のための分子イメージング　　　　　　　　　　　　　　　
佐治英郎, 久下裕司, 向高弘, 多田村栄二, 久米典昭, 野原隆司, INNERVISION, 21, 7, 27, 2006年, ［招待有り］
日本語

“訪問”日本メジフィジックス株式会社 PETラボ（京都ラボ）　　　　　　　　　　　　　　　
久下裕司, Isotope News, 607, 10, 13, 2004年, ［招待有り］

ミニガンマカメラの基礎実験及び臨床への応用の可能性　　　　　　　　　　　　　　　
佐治英郎, 清野 泰, 久下裕司, Isotope News, 606, 2, 6, 2004年, ［招待有り］
日本語

核医学的手法を用いた動脈硬化巣の画像化の可能性
玉木長良, 森田浩一, 竹井俊樹, 久下裕司, 呼吸と循環, 52, 7, 703, 707, 2004年, ［招待有り］
日本語

特集“再生医療と画像診断 −失われた機能の再生をめざして−” 遺伝子治療における画像診断　　　　　　　　　　　　　　　
久下 裕司, 佐治英郎, 清野 泰, 映像情報メディカル, 36, 8, 856, 860, 2004年, ［招待有り］
日本語

PETとレセプター 〜脳と心筋のレセプター機能解析〜　　　　　　　　　　　　　　　
久下 裕司, 玉木 長良, 佐治 英郎, 医薬ジャーナル, 40, 5, 1451, 1457, 2004年, ［招待有り］
日本語

Invited commentary - What is the clinical role of neuronal imaging?
K Morita, Y Kuge, N Tamaki, JOURNAL OF NUCLEAR MEDICINE, 44, 9, 1467, 1468, 2003年09月, ［招待有り］
英語, その他

受容体イメージング　　　　　　　　　　　　　　　
玉木長良, 志賀 哲, 久下裕司, Medical Imaging Technology, 21, 5, 344, 349, 2003年, ［招待有り］
日本語

FDG-PET検査の改良による腫瘍の鑑別診断法の開発：膜輸送遺伝子による検討　　　　　　　　　　　　　　　
玉木長良, 久下裕司, 趙 松吉, 塚本江利子, 中駄邦博, INNERVISION, 18, 8, 25, 2003年, ［招待有り］
日本語

使い捨てFDG合成キット：MicroLab
久下裕司, 西嶋剣一, 玉木長良, RADIOISOTOPES, 51, 191, 195, 2002年, ［招待有り］
日本語

Current status and future of metabolic cardiac imaging
N Tamaki, Y Kuge, C Katoh, NUCLEAR MEDICINE COMMUNICATIONS, 22, 8, 847, 850, 2001年08月, ［招待有り］
英語, その他

The road to quantitation of regional myocardial uptake of tracer
N Tamaki, Y Kuge, E Tsukamoto, JOURNAL OF NUCLEAR MEDICINE, 42, 5, 780, 781, 2001年05月, ［招待有り］
英語, その他

院内製造されたFDGを用いてPET検査を行うためのガイドライン : 日本核医学会
福田 寛, 玉木 長良, 畑澤 順, 井戸 達雄, 遠藤 啓吾, 御前 隆, 石田 良雄, 越智 宏暢, 米倉 義晴, 桑原 康雄, 鳥塚 莞爾, 小西 淳二, 古賀 佑彦, 西村 恒彦, 伊藤 健吾, 岩田 錬, 宇野 公一, 前田 稔, 窪田 和雄, 佐治 英郎, 井上 修, 岡田 昌二, 鈴木 和年, 田中 彰, 安原 眞人, 三宅 義徳, 久下 裕司, 千田 道雄, 伊藤 正敏, 核医学, 38, 2, 131, 137, 2001年03月20日
日本語

PET Summer Seminar Highlights 2001　　　　　　　　　　　　　　　
久下裕司, 塚本江利子, 中駄邦博, 久保直樹, 玉木長良, 映像情報メディカル, 33, 12, 1204, 1210, 2001年, ［招待有り］
日本語

心筋脂肪酸代謝イメージング：123I-BMIPP SPECTと11C-palmitate PET　　　　　　　　　　　　　　　
森田浩一, 久下裕司, 加藤知恵次, 玉木長良, BME, 15, 8, 40, 44, 2001年, ［招待有り］
日本語

Clinical roles of perfusion and metabolic imaging.　　　　　　　　　　　　　　　
Tamaki N, Kuge Y, Tsukamoto E, J Cardiol, 37, Suppl I, 57, 64, 2001年, ［招待有り］
英語

The role of fatty acids in cardiac imaging
N Tamaki, K Morita, Y Kuge, E Tsukamoto, JOURNAL OF NUCLEAR MEDICINE, 41, 9, 1525, 1534, 2000年09月, ［招待有り］
英語

特集“新世紀における核医学の展望―FDG-PETの有用性と経済効果を中心に―” ?-2．使い捨てFDG合成キットの利点と医療経済効果　　　　　　　　　　　　　　　
久下裕司, 塚本江利子, 玉木長良, INNERVISION, 15, 12, 88, 93, 2000年, ［招待有り］
日本語

心臓核医学―治療効果判定のための核医学―
玉木長良, 森田浩一, 久下裕司, 呼吸と循環, 48, 10, 1055, 1059, 2000年, ［招待有り］
日本語

ポジトロン断層撮影法（PET）の虚血性心疾患への応用　　　　　　　　　　　　　　　
玉木長良, 森田浩一, 久下裕司, 塚本江利子, 循環器科, 48, 4, 331, 335, 2000年, ［招待有り］
日本語

特集“21世紀におけるPET画像の役割” 心臓　　　　　　　　　　　　　　　
玉木長良, 森田浩一, 久下裕司, 臨床放射線, 45, 1055, 1064, 2000年, ［招待有り］
日本語

心筋レセプターの核医学イメージング
久下裕司, RADIOISOTOPES, 49, 249, 251, 2000年, ［招待有り］
日本語

動物用PET−脳機能の研究：疾患モデルを用いて　　　　　　　　　　　　　　　
久下裕司, PET通信, 25, 10, 12, 1998年, ［招待有り］
日本語

脳内の酵素活性の核医学イメージング
久下裕司, RADIOISOTOPES, 46, 697, 698, 1997年, ［招待有り］
日本語

PETによる脳内AchEマッピング：アルツハイマー病診断の可能性　　　　　　　　　　　　　　　
久下裕司, ファルマシア, 33, 57, 58, 1997年, ［招待有り］
日本語

ラットのＰＥＴ　　　　　　　　　　　　　　　
久下裕司, 峰松一夫, 長谷川泰弘, 三宅可浩, 循環器病研究の進歩, 17, 85, 91, 1996年, ［招待有り］
日本語

放射線技術学シリーズ：放射化学（改訂4版）　　　　　　　　　　　　　　　
久下裕司, 第8章 4. PETの化学/5.分子イメージング
オーム社, 2023年, ［分担執筆］

わかりやすい核医学 第2版　　　　　　　　　　　　　　　
久下裕司, Ⅰ核医学で知っておくべき最低限の基礎知識 A放射能・放射線の基礎 B放射性医薬 pp2-16
文光堂、東京, 2022年, ［分担執筆］

放射線技術学シリーズ：核医学検査技術学 第4版　　　　　　　　　　　　　　　
久下裕司, 第2章 放射性医薬品 pp.36-44
オーム社、東京, 2022年, ［分担執筆］

Radioimmunodetection of Atherosclerotic Lesions Focusing on the Accumulation Mechanism of Immunoglobulin G　　　　　　　　　　　　　　　
Shimizu Y, Hanzawa H, Zhao Y, Nishijima K, Fukura S, Sakamoto T, Zhao S, Tamaki N, Kuge Y, pp.141-150
Perspectives on Nuclear Medicine for Molecular Diagnosis and Integrated Therapy. (Kuge Y, Shiga T, Tamaki N, eds.), Springer, 2016年, ［共著］

Discovery and Evaluation of Biomarkers for Atherosclerosis　　　　　　　　　　　　　　　
Sakamoto T, Hanzawa H, Manri N, Sakakibara M, Shimizu Y, Zhao Y, Zhao S, Yamada S, Kamiya K, Eki Y, Suzuki A, Higuchi H, Sugano C, Tsutsui H, Tamaki N, Kuge Y, pp.131-139
Perspectives on Nuclear Medicine for Molecular Diagnosis and Integrated Therapy. (Kuge Y, Shiga T, Tamaki N, eds.), Springer, 2016年, ［共著］

Preclinical Evaluation of a Thymidine Phosphorylase Imaging Probe, [123I]IIMU, for Translational Research　　　　　　　　　　　　　　　
Nishijima K, Zhao S, Feng F, Shimizu Y, Akizawa H, Ohkura K, Tamaki N, Kuge Y, pp.125-130
Perspectives on Nuclear Medicine for Molecular Diagnosis and Integrated Therapy. (Kuge Y, Shiga T, Tamaki N, eds.), Springer, 2016年, ［共著］

Development of a Microreactor for Synthesis of 18F-Labeled Positron Emission Tomography Probe　　　　　　　　　　　　　　　
Kuno N, Manri N, Abo N, Asano Y, Nishijima K, Tamaki N, Kuge Y, pp.113-124
Perspectives on Nuclear Medicine for Molecular Diagnosis and Integrated Therapy. (Kuge Y, Shiga T, Tamaki N, eds.), Springer, 2016年, ［共著］

Semiconductor Detector-Based Scanners for Nuclear Medicine　　　　　　　　　　　　　　　
Takeuchi W, Suzuki A, Ueno Y, Shiga T, Hirata K, Okamoto S, Zhao S, Kuge Y, Kubo N, Kobayashi K, Watanabe S, Kobashi K, Umegaki K, Tamaki N, pp.51-65
Perspectives on Nuclear Medicine for Molecular Diagnosis and Integrated Therapy. (Kuge Y, Shiga T, Tamaki N, eds.), Springer, 2016年, ［共著］

Perspectives on Nuclear Medicine for Molecular Diagnosis and Integrated Therapy　　　　　　　　　　　　　　　
Kuge Y, Shiga T, Tamaki N
Springer, 2016年, ［共編者(共編著者)］

放射線技術学シリーズ：核医学検査技術学 第3版 第2章 放射性医薬品　　　　　　　　　　　　　　　
久下裕司, pp.38-45
日本放射線技術学会 監修、大西秀雄・市原 隆・山本智朗 共編。オーム社, 2016年, ［分担執筆］

わかりやすい核医学 ?核医学で知っておくべき最低限の基礎知識 B放射性医薬品　　　　　　　　　　　　　　　
久下裕司, pp.9-15
玉木長良、真鍋治編。文光堂, 2016年, ［分担執筆］

わかりやすい核医学 ?核医学で知っておくべき最低限の基礎知識 A放射能・放射線の基礎　　　　　　　　　　　　　　　
久下裕司, pp.2-8
玉木長良、真鍋治編。文光堂, 2016年, ［分担執筆］

放射線技術学シリーズ：放射化学 第3版 第8章 5.分子イメージング　　　　　　　　　　　　　　　
久下裕司, pp.163-166
日本放射線技術学会 監修、東 静香、久保直樹 共編。オーム社, 2015年, ［分担執筆］

放射線技術学シリーズ：放射化学第3版 第8章 4. PETの化学　　　　　　　　　　　　　　　
久下裕司, pp.152-163
日本放射線技術学会 監修、東 静香、久保直樹 共編。オーム社, 2015年, ［分担執筆］

BRAND NEW 心臓核医学 E心臓核医学の展望。?循環器疾患および動脈硬化の分子イメージング　　　　　　　　　　　　　　　
久下裕司, 玉木長良, pp.248-254
西村恒彦 編。金原出版, 2012年, ［分担執筆］

新・心臓病診療プラクティス16 動脈硬化の内科治療に迫る 核医学検査　　　　　　　　　　　　　　　
玉木長良, 久下裕司, pp.133-138
吉川純一、笠貫宏、土師一夫、別府慎太郎、松崎益徳 編。文光堂, 2011年, ［分担執筆］

ＮＥＷ 放射化学・放射薬品学 第９章 放射線と生体。9.1 身の回りの放射線とその生体への影響　　　　　　　　　　　　　　　
久下裕司, 関興一, pp.209-213
佐治英郎 編。廣川書店, 2011年, ［分担執筆］

Non-invasive Optical Tracking of Bone Marrow Stromal Cells Transplanted into Rat Cerebral Infarct　　　　　　　　　　　　　　　
Sugiyama T, Kuroda S, Osanai T, Maruichi K, Chiba Y, Shichinohe H, Kuge Y, Tamaki N, Iwasaki Y, pp.139-144
Molecular imaging for integrated medical therapy and drug development. (Tamaki N, Kuge Y, eds), Springer, 2010年, ［共著］

Bone Marrow Stromal Cell Transplantation for Central Nervous System Disorders ?Perspective for Translational Research and Clinical Application　　　　　　　　　　　　　　　
Kuroda S, Kuge Y, Tamaki N, Iwasaki Y, pp.126-138
Molecular imaging for integrated medical therapy and drug development. (Tamaki N, Kuge Y, eds), Springer, 2010年, ［共著］

Molecular Imaging of Atherosclerotic Plaque Vulnerability: Comparison between 18F-FDG and 99mTc-Annexin A5　　　　　　　　　　　　　　　
Zhao Y, Kuge Y, Zhao S, Strauss HW, Blankenberg FG, Tamaki N, pp.69-77
Molecular imaging for integrated medical therapy and drug development. (Tamaki N, Kuge Y, eds), Springer, 2010年, ［共著］

Initial Performance Measurement of an Integrated PET/SPECT/CT System for Small Animal Imaging　　　　　　　　　　　　　　　
Magota K, Kubo N, Narihiro K, Suzuki K, Nishijima K, Zhao S, Kuge Y, TamakiN, pp.60-68
Molecular imaging for integrated medical therapy and drug development. (Tamaki N, Kuge Y, eds), Springer, 2010年, ［共著］

Molecular Imaging for the Assessment of Tumor Malignancy and Response to Therapy　　　　　　　　　　　　　　　
Kuge Y, Zhao S, Takei T, Tamaki N, pp.19-29
Molecular imaging for integrated medical therapy and drug development. (Tamaki N, Kuge Y, eds), Springer, 2010年, ［共著］

Advances in Molecular Imaging　　　　　　　　　　　　　　　
Tamaki N, Kuge Y, pp.1-4
Molecular imaging for integrated medical therapy and drug development. (Tamaki N, Kuge Y, eds), Springer, 2010年, ［共著］

Molecular imaging for integrated medical therapy and drug development　　　　　　　　　　　　　　　
Tamaki N, Kuge Y
Springer, 2010年, ［共編者(共編著者)］

遺伝子医学MOOK, 創薬研究への分子イメージング応用 画像バイオマーカーとしての分子イメージングの利用 ７）治療効果評価への分子イメージングの利用 ?動脈硬化治療薬開発のための分子イメージング. 創薬研究への分子イメージング応用　　　　　　　　　　　　　　　
玉木長良, 趙芫, 久下裕司, pp.201-205
佐治英郎 編。メディカル ドゥ, 2010年, ［分担執筆］

遺伝子医学MOOK 別冊, 創薬技術の革新 マイクロドーズからPET分子イメージングへの新展開 PETが着目する課題3）循環器領域の分子イメージング　　　　　　　　　　　　　　　
玉木長良, 吉永恵一郎, 久下裕司, pp.126-131
杉山雄一、山下伸二、栗原千絵子編。メディカル ドゥ, 2010年, ［分担執筆］

心・血管病の分子イメージング 第1章 心・血管病の分子イメージングの歴史、現状　　　　　　　　　　　　　　　
玉木長良, 吉永恵一郎, 久下裕司, pp.1-5
Jagat Narula監修、田原宣広編。永井書店, 2010年, ［分担執筆］

臨床医とコメディカルのための最新クリニカルPET 第18章 心臓核医学の分子イメージング 1.心筋交感神経・受容体イメージング　　　　　　　　　　　　　　　
久下裕司, 西嶋剣一, 玉木長良, pp.288-291
編集主幹：米倉義晴。先端医療技術研究所, 2010年, ［分担執筆］

IAEA RADIOISOTOPES AND RADIOPHARMACEUTICALS SERIES No. 1. Technetium-99m Radiopharmaceuticals: Status and Trends. Chapter 11 Technetium-99m Annexin-A5 for Apoptosis Imaging　　　　　　　　　　　　　　　
Kuge Y, pp.241-253
INTERNATIONAL ATOMIC ENERGY AGENCY, 2009年, ［分担執筆］

放射線技術学シリーズ：放射化学 第2版 第8章4. PETの化学　　　　　　　　　　　　　　　
久下裕司, pp.150-160
日本放射線技術学会 監修、花田博之 編。オーム社, 2008年, ［分担執筆］

放射線技術学シリーズ：放射化学 第2版 第8章5. 分子イメージング　　　　　　　　　　　　　　　
久下裕司, pp.160-163
日本放射線技術学会 監修、花田博之 編。オーム社, 2008年, ［分担執筆］

放射線技術学シリーズ：核医学検査技術学 第2版 第2章 放射性医薬品　　　　　　　　　　　　　　　
久下裕司, pp.36-42
日本放射線技術学会 監修、大西英雄･松本政典･増田一孝 共編。オーム社, 2008年, ［分担執筆］

遺伝子医学MOOK9, ますます広がる分子イメージング技術 第2章 生物学的応用編 4. 心疾患の分子イメージング 2) 神経伝達・受容体機能解析　　　　　　　　　　　　　　　
玉木長良, 久下裕司, pp.232-235
佐治英郎、田畑泰彦 編。メディカル ドゥ, 2008年, ［分担執筆］

臨床医のためのクリニカルPET−病期・病態診断のためのガイドブック− 第I部 基礎・技術編 第1章 PET薬剤の最先端 1. PET薬剤開発の進歩　　　　　　　　　　　　　　　
久下裕司, pp.11-14
伊藤正敏 編、先端医療技術研究所, 2007年, ［分担執筆］

An ultra-high-energy collimator for small animal imaging in dual-isotope study of 18F and 99mTc.　　　　　　　　　　　　　　　
Kubo N, Zhao S, Kinda A, Motomura N, Katoh C, Kuge Y, Tamaki N, pp.275-279
Positron Emission Tomography and Molecular Imaging: State of the Art and Future Perspectives, International Congress Series 1264 (Y. Kuge, N. Tamaki, eds), Elsevier Science B.V, 2004年, ［共著］

Reduction of myocardial oxidative metabolism in dilated cardiomyopathy but not in remote areas in myocardial infarction.　　　　　　　　　　　　　　　
Noriyasu K, Tsukamoto T, Morita K, Kageyama H, Mabuchi M, Katoh C, Kuge Y, Kitabatake A, Tamaki N, pp.271-274
Positron Emission Tomography and Molecular Imaging: State of the Art and Future Perspectives, International Congress Series 1264 (Y. Kuge, N. Tamaki, eds), Elsevier Science B.V, 2004年, ［共著］

In vitro and in vivo characterization of high specific activity S-(-) [11C]CGP-12177, a radioligand for β-adrenoceptors, in rats.　　　　　　　　　　　　　　　
Nishijima K, Kuge Y, Motoki N, Seki K, Ohkura K, Morita K, Tamaki N, pp.261-266
Positron Emission Tomography and Molecular Imaging: State of the Art and Future Perspectives, International Congress Series 1264 (Y. Kuge, N. Tamaki, eds), Elsevier Science B.V, 2004年, ［共著］

The impact of coronary stenosis and risk factors on myocardial flow reserve.　　　　　　　　　　　　　　　
Tsukamoto T, Morita K, Noriyasu K, Katoh C, Kageyama H, Mabuchi K, Kuge Y, Nakada K, Okamoto H, Kitabatake A, Tamaki N, pp.257-260
Positron Emission Tomography and Molecular Imaging: State of the Art and Future Perspectives, International Congress Series 1264 (Y. Kuge, N. Tamaki, eds), Elsevier Science B.V, 2004年, ［共著］

Time course of apoptotic tumor response following a single dose of chemotherapy: Detection with 99mTc-annexin V and comparison with blood flow, caspase-3 expression and TUNEL staining in an experimental tumor model.　　　　　　　　　　　　　　　
Takei T, Kuge Y, Zhao S, Mochizuki T, Strauss HW, Blankenberg F, Tait JF, Tamaki N, pp.249-252
Positron Emission Tomography and Molecular Imaging: State of the Art and Future Perspectives, International Congress Series 1264 (Y. Kuge, N. Tamaki, eds), Elsevier Science B.V, 2004年, ［共著］

Methionine PET in differentiating recurrent brain tumor from radiation necrosis following cranial radiation.　　　　　　　　　　　　　　　
Katoh N, Nakada K, Takei N, Aoyama H, Shirato H, Kato C, Kuge Y, Tsukamoto E, Tamaki N, pp.217-221
Positron Emission Tomography and Molecular Imaging: State of the Art and Future Perspectives, International Congress Series 1264 (Y. Kuge, N. Tamaki, eds), Elsevier Science B.V, 2004年, ［共著］

Neuronal cyclooxygenase-2 induction associated with spreading depression and focal brain ischemia in primates.　　　　　　　　　　　　　　　
Yokota C, Kuge Y, Hasegawa Y, Inoue H, Tagaya M, Abumiya T, Kito G, Tamaki N, Minematsu K, pp.191-196
Positron Emission Tomography and Molecular Imaging: State of the Art and Future Perspectives, International Congress Series 1264 (Y. Kuge, N. Tamaki, eds), Elsevier Science B.V, 2004年, ［共著］

The loss of neuronal integrity may be one of the causes of cognitive disturbances in the patients with brain traumatic injury and normal FLAIR and T2-weighted MRI.　　　　　　　　　　　　　　　
Shiga T, Ikoma K, Tsukamoto M, Katoh C, Matsuyama T, Kuge Y, Nakada K, Tamaki N, pp.177-180
Positron Emission Tomography and Molecular Imaging: State of the Art and Future Perspectives, International Congress Series 1264 (Y. Kuge, N. Tamaki, eds), Elsevier Science B.V, 2004年, ［共著］

Analysis of Neuronal and Glial Functions in Cerebral Ischemia: An Approach with Nuclear Medicine.　　　　　　　　　　　　　　　
Kuge Y, Kaji T, Hikosaka K, Yokota C, Seki K, Ohkura K, Shiga T, Minematsu K, Tamaki N, pp.44-52
Positron Emission Tomography and Molecular Imaging: State of the Art and Future Perspectives, International Congress Series 1264 (Y. Kuge, N. Tamaki, eds), Elsevier Science B.V, 2004年, ［共著］

Clinical Nuclear Cardiology --State of the Art and Future Directions-- (3rd Edition) Section VIII Tracer Specific Imaging Technique, Chapter 35 Fatty Acid Imaging　　　　　　　　　　　　　　　
Tamaki N, Morita K, Kuge Y, pp.559-575
Elsevier, 2004年, ［分担執筆］

Positron Emission Tomography and Molecular Imaging: State of the Art and Future Perspectives　　　　　　　　　　　　　　　
Tamaki N, Kuge Y
International Congress Series 1264, Elsevier Science B.V, 2004年, ［共編者(共編著者)］

クリニカルPET 一望千里 第6章 実用編　　　　　　　　　　　　　　　
河嶋秀和, 久下裕司, pp.179-199
西村恒彦、佐治英郎、飯田秀博編。メジカルレビュー社, 2004年, ［分担執筆］

Brain ischemia and spreading depression in a primate model.　　　　　　　　　　　　　　　
Yokota C, Kuge Y, Tagaya M, Hasegawa Y, Abumiya T, Kito G, Yamaguchi T, Minematsu K, pp.127-144
Strategic medical science against brain attack (Kikuchi H, ed.), Springer-Verlag, 2002年, ［共著］

Annual Review 腎臓 ｢ポジトロン断層撮影法（PET）｣　　　　　　　　　　　　　　　
玉木長良, 塚本江利子, 久下裕司, pp.55-58
伊藤克巳、浅野 泰、遠藤 仁、御手洗哲也、東原英二 編。中外医学社, 2002年, ［分担執筆］

放射線技術学シリーズ：核医学検査技術学 第2章 放射性医薬品　　　　　　　　　　　　　　　
久下裕司, pp.34-44
日本放射線技術学会 監修、大西英雄･松本政典･増田一孝 共編。オーム社, 2002年, ［分担執筆］

循環器疾患---state of arts, ver.2 全面改訂版, 別冊・医学のあゆみ ｢診断法をめぐる最近の進歩, 虚血性心疾患, ポジトロン断層撮影法｣　　　　　　　　　　　　　　　
玉木長良, 久下裕司, pp. 277-279
矢崎義雄、島田和幸、井上博、永井良三 編。医歯薬出版, 2001年, 277-279, ［分担執筆］

放射線技術学シリーズ：放射化学 第6章5. PETの化学　　　　　　　　　　　　　　　
久下裕司, pp.143-154
日本放射線技術学会 監修、花田博之 編。オーム社, 2001年, ［分担執筆］

クリニカルPETハンドブック ｢心筋のバイアビリティ診断、心筋受容体の最近の知見｣　　　　　　　　　　　　　　　
玉木長良, 久下裕司, pp.117-123
鳥塚莞爾、小西淳二、増田康治、西村恒彦、玉木長良、伊藤健吾、佐治英郎 編。技術経済研究所, 2001年, ［分担執筆］

Animal PET Study in Development of Novel PET Tracers.　　　　　　　　　　　　　　　
Kuge Y, Kawashima H, Ejima N, Miyake Y, Hashimoto N, Hashimoto T, Imanishi M, Shiomi M, Minematsu K, Hasegawa Y, Yamaguchi T, Tamaki N, pp.297-304
Positron Emission Tomography in the Millennium”, International Congress Series 1197 (Tamaki N, Tsukamoto E, Kuge Y, Katoh C, Morita K, eds.), Elsevier Science B.V., 2000年, ［共著］

Modified Method for Quantifying Regional Myocardial Blood Flow Using 15O-water with PET　　　　　　　　　　　　　　　
Katoh C, Kuge Y, Morita K, Tsukamoto E, Tamaki N, Knuuti J, pp. 273-278
Positron Emission Tomography in the Millennium”, International Congress Series 1197 (Tamaki N, Tsukamoto E, Kuge Y, Katoh C, Morita K, eds.), Elsevier Science B.V., 2000年, ［共著］

Visualization of Normal Organs in Whole-Body PET Imaging with F-18 FDG　　　　　　　　　　　　　　　
Kato T, Tsukamoto E, Suginami Y, Mabuchi M, Yoshinaga K, Takano A, Adachi I, Shiga T, Morita K, Katoh C, Kuge Y, Tamaki N, pp.221-224
Positron Emission Tomography in the Millennium”, International Congress Series 1197 (Tamaki N, Tsukamoto E, Kuge Y, Katoh C, Morita K, eds.), Elsevier Science B.V., 2000年, ［共著］

Clinical Usefulness of FDC-PET in the Patients with Differentiated Thyroid Cancer after Total Thyroidectomy　　　　　　　　　　　　　　　
Shiga T, Tsukamoto E, Kato T, Morita K, Adachi I, Mabuchi M, Yoshinaga K, Suginami Y, Takano A, Tamaki N, Katoh C, Kuge Y, pp. 181-185
Positron Emission Tomography in the Millennium”, International Congress Series 1197 (Tamaki N, Tsukamoto E, Kuge Y, Katoh C, Morita K, eds.), Elsevier Science B.V., 2000年, ［共著］

Quantitative Analysis for Myocardial Glucose Utilization Using Positron Emission Tomography and F-18-Deoxyglucose　　　　　　　　　　　　　　　
Morita K, Katoh C, Yoshinaga K, Adachi I, Shiga T, Mabuchi M, Itoh Y, Konno M, Kohya T, Kitabatake A, Kuge Y, Tsukamoto E, Tamaki N, pp. 141-145
Positron Emission Tomography in the Millennium”, International Congress Series 1197 (Tamaki N, Tsukamoto E, Kuge Y, Katoh C, Morita K, eds.), Elsevier Science B.V., 2000年, ［共著］

Clinical Utility of Combination of FDG-PET and CBF-SPECT in Extratemporal Lobe Epilepsy　　　　　　　　　　　　　　　
Takano A, Shiga T, Kobayashi J, Nakamura F, Adachi I, Katoh C, Kuge Y, Koyama T, Tsukamoto E, Tamaki N, pp. 73-78
Positron Emission Tomography in the Millennium”, International Congress Series 1197 (Tamaki N, Tsukamoto E, Kuge Y, Katoh C, Morita K, eds.), Elsevier Science B.V., 2000年, ［共著］

Positron Emission Tomography in the Millennium　　　　　　　　　　　　　　　
Tamaki N, Tsukamoto E, Kuge Y, Katoh C, Morita K
International Congress Series 1197, Elsevier Science B.V, 2000年, ［共編者(共編著者)］

フェロトーシス誘導がん治療のPETイメージング　　　　　　　　　　　　　　　
科学研究費助成事業 基盤研究(B)
2021年04月 - 2025年03月
久下 裕司
日本学術振興会, 基盤研究(B), 北海道大学, 21H02858

PETによるフェロトーシスイメージング：動脈硬化プラークの不安定性評価への挑戦　　　　　　　　　　　　　　　
科学研究費助成事業 挑戦的研究(萌芽)
2021年07月 - 2024年03月
久下 裕司
日本学術振興会, 挑戦的研究(萌芽), 北海道大学, 21K19433

サイクロトロンで製造した68Gaを用いる前立腺がん診断用PET薬剤：68Ga-PSMAの標識合成法開発　　　　　　　　　　　　　　　
医療研究開発推進事業費補助金（橋渡し研究戦略的推進プログラム）シーズA支援費
2018年 - 2018年
久下裕司
国立研究開発法人 日本医療研究開発機構, 研究代表者, 競争的資金

オン・デマンドPET検査のための新しいディスポ・チップ型PET薬剤合成装置
科学研究費補助金(挑戦的研究（萌芽)）
2017年 - 2018年
久下 裕司
文部科学省, 研究代表者, 競争的資金

補体複合体のin vivoイメージングによる慢性炎症病態評価法の開発　　　　　　　　　　　　　　　
医療研究開発推進事業費補助金（橋渡し研究戦略的推進プログラム）シーズA支援費
2017年 - 2017年
久下裕司
国立研究開発法人 日本医療研究開発機構, 研究代表者, 競争的資金

動脈硬化の治療戦略に役立つ核医学イメージング法：EBMのための実験的研究
科学研究費補助金(基盤研究(B))
2014年 - 2017年
久下 裕司
文部科学省, 研究代表者, 競争的資金

補体因子Properdinのin vivo可視化による不安定プラーク検出法の開発　　　　　　　　　　　　　　　
医療研究開発推進事業費補助金（橋渡し研加速ネットワークプログラム）シーズAに係る研究開発委託費（シーズ育成経費）
2016年 - 2016年
久下裕司
北海道臨床開発機構, 研究代表者, 競争的資金

動脈硬化症のRI治療への挑戦：マクロファージ浸潤抑制のためのRI内用療法剤の開発
科学研究費補助金(挑戦的萌芽研究)
2015年 - 2016年
久下 裕司
文部科学省, 研究代表者, 競争的資金

新規放射線F-18ラベル法によるDNA取り込み型核酸代謝PET核医学診断薬の開発　　　　　　　　　　　　　　　
医療研究開発推進事業費補助金（橋渡し研加速ネットワークプログラム）シーズAに係る研究開発委託費（シーズ育成経費）
2015年 - 2015年
久下裕司
北海道臨床開発機構, 研究代表者, 競争的資金

慢性炎症の高精度イメージングを可能とする核医学診断材の開発　　　　　　　　　　　　　　　
研究成果展開事業
2014年 - 2015年
久下裕司
科学技術振興機構, 研究代表者, 競争的資金

不安定プラークの特異的イメージング：低分子人工抗体を用いた核医学診断薬の開発
科学研究費補助金(挑戦的萌芽研究)
2013年 - 2014年
久下 裕司
文部科学省, 研究代表者, 競争的資金

不安定プラークの早期・特異的同定：プレターゲティング法による組織因子イメージング
科学研究費補助金(挑戦的萌芽研究)
2011年 - 2012年
久下 裕司
心筋梗塞や脳梗塞の根幹的原因である"動脈内のプラーク"の不安定性を精度よく評価できる診断法の開発が臨床画像診断学の急務である。本研究の目的は、プレターゲティング法を取り入れ、動脈内プラークの破綻とそれに伴う血栓形成に深く関与する組織因子(Tissue Factor, TF)の選択的な描出により不安定プラーク（粥状動脈硬化巣）を特異的に検出しうる新しい核医学イメージング法を提案することにある。この目的達成のため、今年度は以下の研究を実施した。１）anti-TF-mAb-SAv/18F-FBBのシステムの合成検討 18F標識ビオチン誘導体18F-FBBは、プレターゲティングユニットであるanti-TF-mAb-SAvと高い親和性を持つポストプローブであるが、18Fの半減期が約2時間であるため迅速な合成が必要である。この18F-FBBの標識前駆体である18F標識スクシンイミド誘導体18F-SFBの迅速合成のため、合成条件（温度、時間、溶媒等）を詳細に検討した。その結果、[18F]SFBの収量として4.7 ± 0.7 GBq（照射条件25 A, 20 min）、放射化学的収率として33.6 ± 9.5%（減衰補正なし）を達成した。合成時間は約55分程度、HPLCで求めた放射化学的純度は95%以上であり、迅速かつ高純度の[18F]SFBを得ることに成功した。２）モデル動物におけるPET撮像条件・TF発現の検討 TFイメージング実験の前段階として、大腿動脈バルーン障害ウサギを用いて、18F-FDGによるPET撮像実験と、病変部位におけるTF発現の検討を行った。PET撮像実験により200 MBq/rabbit程度の投与量で、動脈硬化病変を明瞭に描出できることが分かった。また、免疫染色により病変部における高いTF発現を認めた。
文部科学省, 研究代表者, 競争的資金

低酸素領域と血管新生因子のダブルターゲティング標識薬剤によるRI治療への挑戦
科学研究費補助金(挑戦的萌芽研究)
2009年 - 2010年
成廣 賢史, 久下 裕司
本研究は、腫瘍における低酸素領域とそれにともない発現する血管新生因子(チミジンボスホリラーゼ:TP)のダブルターゲットとするアイソトープ治療のためのI-131標識薬剤を合成し、その有効性と限界明らかにすることを目的とする。平成21年度において目的とする化合物(5I-6NIMUとI-AIMU)とその合成法を確立した。平成22年度は、その合成法を標識合成法へ応用すべく以下検討を行った。1.放射性ヨウ素標識体5-ヨード-6-ニトロイミダゾールメチルウラシル([^<125>I]5I-6NIMU)の合成6-ニトロイミダゾールメチルウラシルを[^<125>I]NISにより放射性ヨウ素標識化を行った。目的とする[^<125>I]5I-6NIMUの生成を高収率で確認できた。しかしながら単離精製後、溶媒留去の操作において放射化学的純度の低下(分解)が確認された。また、室温下1〜2時間の保存において放射化学的純度の低下を認めた。2.放射性ヨウ素標識体5-ヨード-6-アミノミダゾールメチルウラシル([^<125>I]I-AIMU)標品の合成経路と同様に、[^<125>I]5I-6NIMUをメタノール・アンモニア水中水素雰囲気下10%パラジウム炭素により還元反応を実施した。しかしながら[^<125>I]I-AIMUを得ることに成功していない。その原因として原料[^<125>I]5I-6NIMUおよび成績体[^<125>I]I-AIMUの不安定さが考えられた。5I-6NIMU及びI-AIMUの合成法に従い、放射性ヨウ素を用いた標識合成へ応用した。[^<125>I]5I-6NIMUの放射化学的純度は90%であったが、目的とする放射性ヨウ素化合物を得ることに成功し、アイソトープ治療のためのI-131標識薬剤への展開が示唆された。[^<125>I]I-AIMUを得ることに成功しておらず合成経路を再検討中である。
文部科学省, 研究代表者, 競争的資金

分子イメージングによるがん病態の動的解析:臨床分子イメージングの実現へ向けて
科学研究費補助金(基盤研究(B))
2008年 - 2010年
久下 裕司
本研究では、増殖能・低酸素等を画像化する分子イメージング法による癌の病態解析、及び分子標的治療・放射線治療に対する癌の反応解析の有効性を動物実験・臨床研究において実証した。さらに申請者らが開発してきた“血管新生因子を標的とする分子プローブ"の有効性・安全性を動物において示した。これらの研究成果は、悪性腫瘍の分子レベルの変化を画像化しうる分子イメージング法の特長を生かし、臨床診断への応用が可能な新しい癌の診断・治療法を構築するための重要な知見を提供するものである。
文部科学省, 研究代表者, 競争的資金

脳機能再生機構の解析と分子イメージング~臨床画像診断の実現を目指して~
科学研究費補助金(萌芽研究)
2007年 - 2008年
久下 裕司
本研究の目的は、脳卒中及びアルツハイマー病を対象として、PET・SPECTといった分子イメージング法を分子生物学的手法と融合させることにより脳機能の再生過程を解析し、これらの過程の臨床診断に有用な画像診断法を探索・考案することにある。今年度は、充実した環境(Enriched environment ; EE)及び通常環境の異なる環境下で飼育したラットを用いて、神経機能回復の観点から重要と考えられる梗塞周辺部において、シナプス新生のマーカーであるsynaptophysin (SYP)の発現変化を測定した。また、中枢神経細胞膜上に特異的に発現する中枢性ベンゾジアゼピン受容体を標的とし、これに選択的に結合する[^<125>I]iomazenilを用いたin vitro autoradiographyを行い、環境刺激による神経再構築イメージングの可能性を検討した。その結果、SYP発現密度は、EE群ではST群に比べ、皮質と線条体の梗塞周辺部でともに有意に高く、環境刺激によって梗塞周辺部のシナプス新生が亢進し、これが神経機能の回復に寄与している可能性が示された。また、EE群ではST群に比べ、皮質梗塞周辺部における[^<125>I]iomazenil集積が有意に高く、中枢性ベンゾジアゼピン受容体を指標とする神経機能イメージングにより脳機能の再生過程を解析できる可能性が示された。以上の結果より、放射性iomazenilなどのプローブを用いた核医学的手法により、脳虚血障害後の環境刺激による神経機能の回復を定量的に評価できる可能性が示された。
文部科学省, 研究代表者, 競争的資金

分子イメージングとがん治療戦略:イメージングによるインビボ組織染色を目指して
科学研究費補助金(基盤研究(B))
2005年 - 2007年
久下 裕司
本研究では、"がんの分子機構"や"がんの個性"に関する情報を、ポジトロンCTをはじめとする分子イメージング法を用いてインビボで画像として捉え、がんの治療戦略に役立てることを目的とし、以下の成果を得た。1.分子標的治療に関する研究動物実験において、FLT(核酸誘導体)は腫瘍細胞の増殖能を反映し、Iressaなど分子標的療法の早期治療効果判定に有用である可能性が示された。2.放射線治療に関する研究担がんモデルラットにおいて、放射線照射による炎症反応が惹起される前にFDGにより放射線治療の効果を評価しうる可能性が示唆された。3.がんの分子機構を標的とする新規分子イメージング剤の開発(1)がんの血管新生能の評価を目的とした分子イメージング用薬剤として、チミジンホスホリラーゼ(TP)阻害作用を有する核酸誘導体の合成、及びC-11, I-123標識に成功した。これらの化合物は母体化合物と同等のTP阻害能を有した。(2)Celecoxibの放射性ヨウ素標識体(IMTP)のシクロオキシゲナーゼ-2イメージング用薬剤としての有用性が示唆された。また、非特異的集積の低減を目指して設計・合成した、新規ヨウ素標識体はCOX-2に高い選択性と阻害活性、非特異的結合の低下を示し、[^<123>I]FIMAがCOX-2選択的イメージング剤となる得ることが示唆された。(3)[^<99m>Tc]標識抗MT1-MMP抗体は腫瘍への集積性を示し、Membrane-type 1 matrix metalloproteinase (MT1-MMP)を標的としたイメージング剤としての有用性が示唆された。また、プレターゲティング法を用いることで、S/N比が改善する可能性が示唆された。
文部科学省, 研究代表者, 競争的資金

マイクロリアクタによるポジトロンプローブの合成:チップ型自動合成装置の開発へ
科学研究費補助金(萌芽研究)
2006年 - 2006年
久下 裕司
本研究では、マイクロリアクタを用いる合成技術をポジトロンプローブ合成に応用することにより、簡便・迅速な標識合成法を確立し、チップ型自動合成装置開発の可能性を探ることを目的とし、以下の検討を行った。すなわち、反応系の制御に優れたマイクロリアクターを用いることで、PET用ドパミンD2受容体イメージング薬である[11C]ラクロプライドを短時間内に効率的に合成しうるか否かを検討した。マイクロリアクターには、Y字型チャネル構造のチップ(200um(W)×20um(D)×250mm(L))を用いた。原料としてデスメチルラクロプライド(2mg/800ul)と[11C]ヨウ化メチルの各DMSO溶液を用意し、これを2つの注入口からそれぞれ導入し、反応させた。チップの出口より採取した反応液をHPLCにて分析し、[11C]ラクロプライドの収率を算出した。また、原料の注入速度、反応温度と収率との関係を検討した。その結果、マイクロリアクターでの室温における収率は20secで11.7±4.3%、60secで14.5±2.3%であり、短時間での高収率、かつ良好な再現性を認めた。一方、60℃における収率は、20secで20.3±2.0%であり、加温による収率のさらなる上昇を認めた。以上の結果は、マイクロリアクターを用いた効率的な[11C]ラクロプライド合成を示すものであり、本システムを応用することで、今後放射性プローブを簡便に供給できる可能性が示された。
文部科学省, 研究代表者, 競争的資金

動脈硬化病態の解析と分子イメージング:プロスタグランジン合成酵素を標的として
科学研究費補助金(萌芽研究)
2004年 - 2005年
久下 裕司
本研究では、動脈硬化モデルにおいて放射性標識COX-2阻害薬の動態を解析し、分子生物学的評価結果と対比することにより、COX-2を標的とする動脈硬化病態診断の可能性を検証することを目的とし、本年度は以下の検討を行った。1.COX-2を標的とする放射性薬剤の開発に関する検討昨年度までに、選択的COX-2阻害薬であるCelecoxibのヨウ素置換体(IMTP)をデザイン・合成した。今年度は、IMTPの分子イメージング剤としての有用性をさらに検証するため、ラットを用いてインビボでの評価を行った。その結果、IMTPは速やかな血中クリアランスを示し、優れた標的/血液比を示した。これらの結果より、IMTPのCOX-2選択的イメージング剤としての可能性がインビボ実験において示された。2.動脈硬化モデルウサギにおけるCOX-2発現の検討動脈硬化病態、特に、プラーク破綻には、細胞外マトリックス分解酵素(MMP)が深く関与している。最近、MMPがプロスタグランジン(PG)E2依存性の経路により産生されることが示され、PGE2合成の律速酵素であるCOX、特に誘導型であるCOX-2の役割が注目されつつある。そこで、動脈硬化モデル家兎においてCOX-2発現を解析し、MMP-2の発現と対比することにより、COX-2を標的とする動脈硬化病態診断の有用性を検証した。その結果、MMP-2は、最も不安定性を示すアテローム性病変に強く発現していた。一方、COX-2は初期病変から進行性病変にわたって広く発現していた。これらの結果は、COX-2を標的とする分子イメージングにより動脈硬化病変の早期検出が可能であり、他方、MMP-2イメージングでは進行性病変の描出が可能であることを示唆している。
文部科学省, 研究代表者, 競争的資金

脳虚血病態の解析と分子イメージング:プロスタグランジン合成酵素を標的として
科学研究費補助金(基盤研究(B))
2002年 - 2004年
久下 裕司
分子生物学的研究にインビボ分子イメージングの手法を組み入れ、(1)局所脳虚血病態に対するシクロオキシゲナーゼ-2 (COX-2)の組織障害性作用と脳組織再生作用を解析し、COX-2の作用とその阻害薬の役割を明らかにすること、(2)COX-2を標的とした分子イメージング法による脳虚血病態診断の可能性を探ることを目的として研究を遂行し、以下の成果を得た。1.脳虚血モデル動物における脳循環代謝、神経受容体機能の経時的変化の検討ベンゾジアゼピン受容体機能が保たれた虚血領域では、DNA断片化や細胞構築の破壊は見られなかった。他方、ベンゾジアゼピン受容体機能低下の見られない虚血領域にもCOX-2発現が認められた。2.脳虚血モデル動物におけるCOX-2,プロスタグランジン類の経時的変化の検討(1)COX-2 mRNA, COX-2 proteinの発現パターンは、血流低下の著しい虚血中心部とその周辺部では明らかに異なっており、COX-2発現が虚血の程度と時間によりダイナミックに変化していることが示唆された。(2)選択的COX-2阻害薬によるCOX-2活性の抑制は、SD誘発側皮質のIL1β、IL6発現とS100A9遺伝子の両側性発現抑制を伴うことが示唆された。3.COX-2を標的とした分子イメージング法に関する検討構造-活性相関学的検討から、選択的COX-2阻害薬であるCelecoxibのヨウ素置換体、5-(4-[^<123>I]iodophenyl)-1-[4-(methylsulfonyl)phenyl]-3-trifluoromethyl- 1H-pyrazole([^<123>I]IMTP)をデザイン・合成した。さらに、本化合物の分子イメージング剤としての有用性を検討した結果、IMTPがCOX-2に対して高い選択性と阻害活性を有することを見い出し、その放射性ヨウ素標識に成功した。
文部科学省, 研究代表者, 競争的資金

核酸合成・PG合成酵素のインビボイメージング:腫瘍・炎症の鑑別診断への挑戦
科学研究費補助金(萌芽研究)
2002年 - 2003年
久下 裕司
腫瘍と炎症を精度良く鑑別し、治療方針の決定に役立てることが、診断医学の最重要課題の一つである。申請者らは、核酸合成及びプロスタグランジン合成酵素(COX)を標的とし、ポジトロン断層撮影法(PET)、シングルフォトン断層撮影法(SPECT)による腫瘍/炎症の鑑別診断能を向上させることを目的として本研究を計画した。この目的を達成するため、本年度は以下の検討を行った。(1)[C-11]ホスゲンを用いる核酸誘導体の簡便な標識合成法の開発研究数種の標識前駆物質を合成し、チミン、チミジンの非標識合成及びC-11標識合成を試みた。その結果、新規に合成された標識前駆物質により非標識チミンの合成に成功した。さらに、この標識前駆物質と[C-11]ホスゲンとの反応により[C-11]チミン、[C-11]チミジンの合成に成功した。(2)COX阻害薬の放射標識合成法の開発研究構造-活性相関学的検討から、選択的COX-2阻害薬であるCelecoxibのヨウ素置換体をデザインした。さらに、放射性ヨウ素標識体を得るため、数種の標識前駆物質の合成、及びヨウ素置換体の合成を試み、これらに成功した。(3)モデル動物に関する検討核酸合成及びプロスタグランジン合成酵素を標的とする腫瘍診断の有用性を評価するため、対照として糖代謝、アポトーシス、及び低酸素マーカーの腫瘍・炎症内分布をモデル動物において測定した。現在、上記(1)(2)に記載した標識化合物の腫瘍・炎症内分布を検討中である。
文部科学省, 研究代表者, 競争的資金

腫瘍/炎症内ブドウ糖代謝・膜輸送遺伝子と背景因子:腫瘍鑑別診断のための基礎的研究
科学研究費補助金(奨励研究(A))
2000年 - 2001年
久下 裕司
^<18>F-FDGを用いるPET検査は、悪性腫瘍の鑑別診断、治療効果判定などにおいてきわめて有効性が高い。しかし、^<18>F-FDGは一部良性疾患にも集積することが明らかとなり、本検査による腫瘍鑑別診断の限界が指摘されている。これらの鑑別診断をより的確に行うには、悪性腫瘍や良性疾患への^<18>F-FDGの集積機序を明らかにすることが必須である。一方、最近、腫瘍・炎症へのFDG集積にはGlucose transporter(GLUT)が関与していることが明らかとなってきた。本研究では、腫瘍、感染性炎症、非特異的炎症モデルラットを用い、実験的腫瘍及び炎症組織におけるFDG集積とGLUT発現に及ぼすインシュリン及びグルコース負荷の影響を検討した。1.インシュリン負荷により腫瘍及び両炎症へのFDG集積は対照の約50%に低下したが、GLUT発現には大きな影響は与えなかった。2.グルコース負荷時のFDG集積は両炎症で対照の約50%、腫瘍で約85%であった。このとき、非特異的炎症ではGLUT1発現が有意に低下し、感染性炎症ではGLUT3発現が有意に低下した。GLUT1とGLUT3の発現は腫瘍では変化しなかった。したがって、グルコース負荷は腫瘍、炎症の鑑別診断の手がかりになる可能性がある。
文部科学省, 研究代表者, 競争的資金