Ogawa Mikako
| Faculty of Pharmaceutical Sciences Biopharmaceutical Sciences and Pharmacy Biopharmaceutical Sciences and Pharmacy | Professor |
| Institute for Integrated Innovations Institute for Chemical Reaction Design and Discovery | Professor |
Last Updated :2025/11/06
■Researcher basic information
Researchmap personal page
Researcher number
- 20344351
J-Global ID
Educational Organization
- Bachelor's degree program, School of Pharmaceutical Sciences and Pharmacy
- Master's degree program, Graduate School of Life Science
- Doctoral (PhD) degree program, Graduate School of Life Science
■Career
Position History
■Research activity information
Papers
- Effect of hydroxy groups on X-ray-induced reactions of azo benzene derivatives
Koki Ogawara, Naoya Ieda, Hideo Takakura, Kohei Nakajima, Akari Mukaimine, Mei Harada, Kazuaki Hashimoto, Osamu Inanami, Mikako Ogawa
Organic & Biomolecular Chemistry, Royal Society of Chemistry (RSC), 2025
Scientific journal, We investigated the role of the hydroxy group in the cleavage of the azo bond with X-rays. From the results of the product analysis, it was suggested that nonspecific degradation is promoted as the number of hydroxy groups increases. - Piperazine based pH-responsive cyanine dyes for cancer cell photoacoustic imaging
Koki Tsuchiya, Hideo Takakura, Kohei Nakajima, Naoya Ieda, Takashi Kaneko, Takeshi Hirasawa, Masato Kobayashi, Yoshihisa Yamaoka, Miya Ishihara, Tetsuya Taketsugu, Mikako Ogawa
Journal of Photochemistry and Photobiology A: Chemistry, 453, 115634, 115634, Elsevier BV, Aug. 2024
Scientific journal - Investigation of the substituent effect of indocyanine green derivatives for lymph imaging
Naoya Ieda, Hideo Takakura, Hirotaka Maeta, Takayuki Ohira, Koki Tsuchiya, Kohei Nakajima, Mikako Ogawa
Bioorganic & Medicinal Chemistry, 117824, 117824, Elsevier BV, Jun. 2024
Scientific journal - 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, Jun. 2024
Scientific journal - Development of small molecule–drug conjugates based on derivatives of natural proteasome inhibitors that exhibit selectivity for PSMA-expressing cancer cells
Takahiro Obara, Nanami Kawano, Kengo Tatsumi, Akira Katsuyama, Kohei Nakajima, Mikako Ogawa, Satoshi Ichikawa
Bioorganic & Medicinal Chemistry, 108, 117773, 117773, Elsevier BV, Jun. 2024
Scientific journal - Development of a red-shifted photosensitizer for near-infrared photoimmunotherapy of cancer
Yuto Goto, Kanta Ando, Hideo Takakura, Kohei Nakajima, Masato Kobayashi, Osamu Inanami, Tetsuya Taketsugu, Mikako Ogawa
Journal of Photochemistry and Photobiology, 20, 100230, 100230, Elsevier BV, Apr. 2024
Scientific journal - Theoretical Design and Synthesis of Caged Compounds Using X‐Ray‐Triggered Azo Bond Cleavage
Koki Ogawara, Osamu Inanami, Hideo Takakura, Kenichiro Saita, Kohei Nakajima, Sonu Kumar, Naoya Ieda, Masato Kobayashi, Tetsuya Taketsugu, Mikako Ogawa
Advanced Science, Wiley, 15 Jan. 2024
Scientific journal, Abstract
Caged compounds are frequently used in life science research. However, the light used to activate them is commonly absorbed and scattered by biological materials, limiting their use to basic research in cells or small animals. In contrast, hard X‐rays exhibit high bio‐permeability due to the difficulty of interacting with biological molecules. With the main goal of developing X‐ray activatable caged compounds, azo compounds are designed and synthesized with a positive charge and long π‐conjugated system to increase the reaction efficiency with hydrated electrons. The azo bonds in the designed compounds are selectively cleaved by X‐ray, and the fluorescent substance Diethyl Rhodamine is released. Based on the results of experiments and quantum chemical calculations, azo bond cleavage is assumed to occur via a two‐step process: a two‐electron reduction of the azo bond followed by N─N bond cleavage. Cellular experiments also demonstrate that the azo bonds can be cleaved intracellularly. Thus, caged compounds that can be activated by an azo bond cleavage reaction promoted by X‐ray are successfully generated. - Novel Auger-Electron-Emitting 191Pt-Labeled Pyrrole-Imidazole Polyamide Targeting MYCN Increases Cytotoxicity and Cytosolic dsDNA Granules in MYCN-Amplified Neuroblastoma.
Honoka Obata, Atsushi B Tsuji, Hitomi Sudo, Aya Sugyo, Kaori Hashiya, Hayato Ikeda, Masatoshi Itoh, Katsuyuki Minegishi, Kotaro Nagatsu, Mikako Ogawa, Toshikazu Bando, Hiroshi Sugiyama, Ming-Rong Zhang
Pharmaceuticals (Basel, Switzerland), 16, 11, 27 Oct. 2023, [International Magazine]
English, Scientific journal, Auger electrons can cause nanoscale physiochemical damage to specific DNA sites that play a key role in cancer cell survival. Radio-Pt is a promising Auger-electron source for damaging DNA efficiently because of its ability to bind to DNA. Considering that the cancer genome is maintained under abnormal gene amplification and expression, here, we developed a novel 191Pt-labeled agent based on pyrrole-imidazole polyamide (PIP), targeting the oncogene MYCN amplified in human neuroblastoma, and investigated its targeting ability and damaging effects. A conjugate of MYCN-targeting PIP and Cys-(Arg)3-coumarin was labeled with 191Pt via Cys (191Pt-MYCN-PIP) with a radiochemical purity of >99%. The binding potential of 191Pt-MYCN-PIP was evaluated via the gel electrophoretic mobility shift assay, suggesting that the radioagent bound to the DNA including the target sequence of the MYCN gene. In vitro assays using human neuroblastoma cells showed that 191Pt-MYCN-PIP bound to DNA efficiently and caused DNA damage, decreasing MYCN gene expression and MYCN signals in in situ hybridization analysis, as well as cell viability, especially in MYCN-amplified Kelly cells. 191Pt-MYCN-PIP also induced a substantial increase in cytosolic dsDNA granules and generated proinflammatory cytokines, IFN-α/β, in Kelly cells. Tumor uptake of intravenously injected 191Pt-MYCN-PIP was low and its delivery to tumors should be improved for therapeutic application. The present results provided a potential strategy, targeting the key oncogenes for cancer survival for Auger electron therapy. - Near-infrared photoimmunotherapy and anti-cancer immunity
Kohei Nakajima, Mikako Ogawa
International Immunology, Oxford University Press (OUP), 16 Oct. 2023
Scientific journal, Abstract
The activation of the anti-cancer immune system is an important strategy to control cancer. A new form of cancer phototherapy, near-infrared photoimmunotherapy (NIR-PIT), was approved for clinical use in 2020 and uses IRDye® 700DX (IR700)-conjugated antibodies and NIR light. After irradiation with NIR light, the antibody–IR700 conjugate forms water-insoluble aggregations on the plasma membrane of target cells. This aggregation causes lethal damage to the plasma membrane, and effectively leads to immunogenic cell death (ICD). Subsequently, ICD activates anti-cancer immune cells such as dendritic cells and cytotoxic T cells. Combination therapy with immune-checkpoint blockade has synergistically improved the anti-cancer effects of NIR-PIT. Additionally, NIR-PIT can eliminate immunosuppressive immune cells in light-irradiated tumors by using specific antibodies against regulatory T cells and myeloid-derived suppressor cells. In addition to cancer-cell-targeted NIR-PIT, such immune-cell-targeted NIR-PIT has shown promising results by activating the anti-cancer immune system. Furthermore, NIR-PIT can be used to manipulate the tumor microenvironment by eliminating only targeted cells in the tumor, and thus it also can be used to gain insight into immunity in basic research. - 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, 16 May 2023
Scientific journal - X線によるアゾ結合の開裂により活性化されるケージド化合物の開発
小河原 浩輝, 高倉 栄男, 中島 孝平, 斉田 謙一郎, Kumar Sonu, 小林 正人, 武次 徹也, 稲波 修, 小川 美香子
JSMI Report, 16, 2, 64, 64, 日本分子イメージング学会, May 2023
Japanese - 潰瘍性大腸炎におけるニコチンの抗炎症作用に関する[18F]FDGを用いた検討
吉野 元貴, 中島 孝平, 高倉 栄男, 小川 美香子
JSMI Report, 16, 1, 21, 25, Feb. 2023, [Peer-reviewed]
Japanese - Application of Imaging for Antibody-Based Cancer Therapies : Photoimmunotherapy and Immune Checkpoint Blockade Therapy
Kohei NAKAJIMA, Mikako OGAWA
Journal of the Imaging Society of Japan, 61, 6, 643, 651, 10 Dec. 2022, [Peer-reviewed]
English, Scientific journal - Dynamic imaging analysis reveals Auger electron-emitting radio-cisplatin induces DNA damage depending on the cell cycle
Honoka Obata, Akihiro Kurimasa, Tadanori Muraoka, Atsushi B. Tsuji, Katsuya Kondo, Yoshikazu Kuwahara, Katsuyuki Minegishi, Kotaro Nagatsu, Mikako Ogawa, Ming-Rong Zhang
Biochemical and Biophysical Research Communications, 637, 286, 293, Elsevier BV, Dec. 2022
Scientific journal - Precise quantitative evaluation of pharmacokinetics of cisplatin using a radio-platinum tracer in tumor-bearing mice.
Honoka Obata, Atsushi B Tsuji, Hitomi Sudo, Aya Sugyo, Katsuyuki Minegishi, Kotaro Nagatsu, Mikako Ogawa, Ming-Rong Zhang
Nuclear medicine communications, 43, 11, 1121, 1127, 01 Nov. 2022, [International Magazine]
English, Scientific journal, OBJECTIVE: The platinum-based antineoplastic drug cisplatin is commonly used for chemotherapy in clinics. This work aims to demonstrate a radio-platinum tracer is useful for precisely quantifying small amounts of platinum in pharmacokinetics studies. METHODS: A cisplatin radiotracer (radio-cisplatin) was synthesized, and a comprehensive evaluation of cisplatin over 7 days after its intravenous injection into nude mice bearing a subcutaneous lung tumor (H460) was conducted. RESULTS: A biphasic retention curve in the whole body and blood was observed [ T1/2 (α) = 1.14 h, T1/2 (β) = 5.33 days for the whole body, and T1/2 (α) = 23.9 min, T1/2 (β) = 4.72 days for blood]. The blood concentration decreased within 1 day after injection. Most of the intact cisplatin was excreted via the kidneys in the early time points, and a small part was distributed in tissues including tumors. The plasma protein binding rate of cisplatin increased rapidly after injection, and the protein-bound cisplatin remained in the blood longer than intact cisplatin. The peak uptake in H460 tumors was 4.7% injected dose per gram at 15 min after injection, and the area under the curve (AUC 0-7 days ) was approximately one-half to one-third of the AUC 0-7 days in the kidneys, liver, and bone, where some toxicity is observed in humans. CONCLUSION: The radio-platinum tracer revealed the highly quantitative biodistribution of cisplatin, providing insights into the properties of cisplatin, including its adverse effects. The tracer enables a precise evaluation of pharmacokinetics for platinum-based drugs with high sensitivity. - 低酸素条件下のがん細胞に対する光免疫療法(PIT)の有効性の評価
白川 晴香, 後藤 悠人, 中島 孝平, 高倉 栄男, 安井 博宣, 小川 美香子, 稲波 修
日本獣医学会学術集会講演要旨集, 165回, [I1A, 12], (公社)日本獣医学会, Sep. 2022
Japanese - 腫瘍内の低酸素状態に抗PD-1療法が及ぼす影響に関する検討(Reduction of tumor hypoxia during anti-PD-1 therapy in a CT26 colon cancer model)
中島 孝平, 鈴木 基史, 高倉 栄男, 久下 裕司, 小川 美香子
日本癌学会総会記事, 81回, P, 2194, (一社)日本癌学会, Sep. 2022
English - Ligand release from silicon phthalocyanine dyes triggered by X-ray irradiation.
Hideo Takakura, Shino Matsuhiro, Osamu Inanami, Masato Kobayashi, Kenichiro Saita, Masaki Yamashita, Kohei Nakajima, Motofumi Suzuki, Naoki Miyamoto, Tetsuya Taketsugu, Mikako Ogawa
Organic & biomolecular chemistry, 16 Aug. 2022, [International Magazine]
English, Scientific journal, Ligand release from silicon phthalocyanine (SiPc) dyes triggered by near-infrared (NIR) light is a key photochemical reaction involving caged compounds based on SiPc. Although NIR light is relatively permeable compared with visible light, this light can be attenuated by tissue absorption and scattering; therefore, using light to induce photochemical reactions deep inside the body is difficult. Herein, because X-rays are highly permeable and can produce radicals through the radiolysis of water, we investigated whether the axial ligands of SiPcs can be cleaved using X-ray irradiation. SiPcs with different axial ligands (alkoxy, siloxy, oxycarbonyl, and phenoxy groups) were irradiated with X-rays under hypoxic conditions. We found that the axial ligands were cleaved via reactions with hydrated electrons (e-aq), not OH radicals, generated from water in response to X-ray irradiation, and SiPc with alkoxy groups exhibited the highest cleavage efficiency. A quantitative investigation revealed that X-ray-induced axial ligand cleavage proceeds via a radical chain reaction. The reaction is expected to be applicable to the molecular design of X-ray-activatable functional molecules in the future. - 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, 15 Aug. 2022, [Domestic magazines]
English, Scientific journal, 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. - 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, May 2022
Scientific journal - Development of Novel 191Pt-Labeled Hoechst33258: 191Pt Is More Suitable than 111In for Targeting DNA.
Honoka Obata, Atsushi B Tsuji, Katsushi Kumata, Hitomi Sudo, Katsuyuki Minegishi, Kotaro Nagatsu, Hideo Takakura, Mikako Ogawa, Akihiro Kurimasa, Ming-Rong Zhang
Journal of medicinal chemistry, 65, 7, 5690, 5700, 14 Apr. 2022, [International Magazine]
English, Scientific journal, This study aims to establish new labeling methods for no-carrier-added radio-Pt (191Pt) and to evaluate the in vitro properties of 191Pt-labeled agents compared with those of agents labeled with the common emitter 111In. 191Pt was complexed with the DNA-targeting dye Hoechst33258 via diethylenetriaminepentaacetic acid (DTPA) or the sulfur-containing amino acid cysteine (Cys). The intranuclear fractions of 191Pt- and 111In-labeled Hoechst33258 were comparable, indicating that the labeling for 191Pt via DTPA or Cys and the labeling for 111In via DTPA worked equally well. 191Pt showed a DNA-binding/cellular uptake ratio of more than 1 order of magnitude greater than that of 111In. [191Pt]Pt-Hoechst33258 labeled via Cys showed a higher cellular uptake than that labeled via DTPA, resulting in a very high DNA-binding fraction of [191Pt]Pt-Cys-Hoechst33258 and extensive DNA damage. Our labeling methods of radio-Pt, especially via Cys, promote the development of radio-Pt-based agents for use in Auger electron therapy targeting DNA. - Axial-ligand-cleavable silicon phthalocyanines triggered by near-infrared light toward design of photosensitizers for photoimmunotherapy
Hideo Takakura, Shino Matsuhiro, Masato Kobayashi, Yuto Goto, Mei Harada, Tetsuya Taketsugu, Mikako Ogawa
Journal of Photochemistry and Photobiology A: Chemistry, 426, 113749, 113749, Elsevier BV, Apr. 2022
Scientific journal - 免疫チェックポイント阻害剤が腫瘍内の低酸素状態に及ぼす影響に関する検討
本間 充憲, 中島 孝平, 鈴木 基史, 横内 勇太, 松田 拓真, 高倉 栄男, 平田 健司, 久下 裕司, 小川 美香子
日本薬学会年会要旨集, 142年会, 26H, pm06S, (公社)日本薬学会, Mar. 2022
Japanese - New cancer therapy with Illuminox<sup>Ⓡ</sup> platform
Kohei Nakajima, Mikako Ogawa
Drug Delivery System, 37, 1, 72, 77, Japan Society of Drug Delivery System, 25 Jan. 2022
Scientific journal - Correction: In Vitro and In Vivo Cell Uptake of a Cell-Penetrating Peptide Conjugated with Fluorescent Dyes Having Different Chemical Properties (Cancers, (2021), 13, 2245, 10.3390/cancers13092245)
Takakura, H., Sato, H., Nakajima, K., Suzuki, M., Ogawa, M.
Cancers, 14, 8, 2022
Scientific journal - EPR Characterisation of Phthalocyanine Radical Anions in Near‐Infrared Photocleavage of the Hydrophilic Axial Ligand of a Photoimmunotherapeutic Reagent, IR700
Osamu Inanami, Wakako Hiraoka, Yuto Goto, Hideo Takakura, Mikako Ogawa
ChemPhotoChem, Wiley, 15 Nov. 2021
Scientific journal - Electron Donors Rather Than Reactive Oxygen Species Needed for Therapeutic Photochemical Reaction of Near-Infrared Photoimmunotherapy.
Takuya Kato, Ryuhei Okada, Yuto Goto, Aki Furusawa, Fuyuki Inagaki, Hiroaki Wakiyama, Hideyuki Furumoto, Dagane Daar, Baris Turkbey, Peter L Choyke, Hideo Takakura, Osamu Inanami, Mikako Ogawa, Hisataka Kobayashi
ACS pharmacology & translational science, 4, 5, 1689, 1701, 08 Oct. 2021, [International Magazine]
English, Scientific journal, Near-infrared photoimmunotherapy (NIR-PIT) employs molecularly targeted antibodies conjugated with a photoabsorbing silicon-phthalocyanine dye derivative which binds to cancer cells. Application of NIR light following binding of the antibody-photoabsorber conjugates (APCs) results in ligand release on the dye, dramatic changes in solubility of the APC-antigen complex, and rapid, irreversible cell membrane damage of cancer cells in a highly selective manner, resulting in a highly immunogenic cell death. Clinically, this process results in edema after treatment mediated by reactive oxygen species (ROS). Based on the chemical and biological mechanism of NIR-PIT cytotoxicity and edema formation, in order to minimize acute inflammatory edema without compromising therapeutic effects, l-sodium ascorbate (l-NaAA) was administered to quench harmful ROS and accelerate the ligand release reaction. l-NaAA suppressed acute edema by reducing ROS after NIR-PIT yet did not alter the therapeutic effects. NIR-PIT could be performed safely under existence of l-NaAA without side effects caused by unnecessary ROS production. - PETイメージング剤を用いた動脈硬化プラークにおけるニコチン受容体の発現に関する検討
鈴木 基史, 片山 竜樹, 鈴木 千恵, 中島 孝平, 間賀田 泰寛, 小川 美香子
日本動脈硬化学会総会プログラム・抄録集, 53回, 195, 195, (一社)日本動脈硬化学会, Oct. 2021
Japanese - Uptake of nicotinic acetylcholine receptor imaging agent is reduced in the pro-inflammatory macrophage.
Motofumi Suzuki, Tatsuki Katayama, Chie Suzuki, Kohei Nakajima, Yasuhiro Magata, Mikako Ogawa
Nuclear medicine and biology, 102-103, 45, 55, 29 Sep. 2021, [International Magazine]
English, Scientific journal, INTRODUCTION: Macrophages play a vital role in the development of atherosclerotic cardiovascular disease. Macrophages are functionally and phenotypically heterogeneous immune cells and commonly exist in two distinct or polarized subsets: pro-inflammatory M1 and anti-inflammatory M2 phenotypes. Previous reports suggest that stimulation of α7 or α4β2 nicotinic acetylcholine receptors (nAChRs) in macrophages leads to an anti-inflammatory response. However, the biological link between nAChR expression on macrophages and the polarization state is unknown. Therefore, we evaluated the relationship between nAChRs and polarized macrophages in peritoneal macrophages and atherosclerotic plaques of apolipoprotein E knockout (ApoE-/-) mice. METHODS: Peritoneal macrophages isolated from mice were polarized into M1 and M2 macrophages, and the uptake of the nAChR-imaging agents, (R)-2-[11C]methylamino-benzoic acid 1-aza-bicyclo[2.2.2]oct-3-yl ester ([11C]MeQAA) or 2-[18F]fluoro-3-(2(S)-azetidinylmethoxy) pyridine ([18F]2FA), and 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) was assessed. We also evaluated the accumulation of imaging agents in atherosclerotic plaques of ApoE-/- mice by autoradiography. After an autoradiogram was obtained, the same aortic tissue was used for immunohistochemical staining of CD68, inducible nitric oxide synthase (iNOS), and arginine-1. RESULTS: In an in vitro assay, the uptake of [11C]MeQAA or [18F]2FA was lower in M1 than in M0 and M2 macrophages. In comparison, the uptake of [18F]FDG was higher in M1 macrophages. Ex vivo autoradiography showed that [11C]MeQAA was localized to the extensive plaque area. By contrast, the accumulation of [18F]2FA and [18F]FDG was heterogeneous and found only in some plaques. Moreover, the expression of CD68 and iNOS was higher in [18F]2FA non-uptake than [18F]2FA uptake plaques. CONCLUSION: Macrophage polarization was related to nAChR expression, and α4β2 nAChR expression was suppressed in the M1 macrophage. These findings suggest that nAChR imaging has the potential to identify the inflammatory status of atherosclerotic plaque. - Comparison of low-molecular-weight ligand and whole antibody in prostate-specific membrane antigen targeted near-infrared photoimmunotherapy.
Kohei Nakajima, Fuka Miyazaki, Kazuki Terada, Hideo Takakura, Motofumi Suzuki, Mikako Ogawa
International journal of pharmaceutics, 609, 121135, 121135, 24 Sep. 2021, [International Magazine]
English, Scientific journal, Near-infrared photoimmunotherapy (NIR-PIT) is a cancer phototherapy that uses antibody-IR700 conjugate (Ab-IR700) and NIR light. Ab-IR700 forms aggregates on the plasma membranes of targeted cancer cells after light exposure, inducing lethal physical damage within the membrane. Low-molecular-weight (LMW) ligands are candidate targeting moieties instead of antibodies, but whether LMW-IR700 conjugates induce cell death by aggregation, the same mechanism as Ab-IR700, is unknown. Thus, we investigated differences in cytotoxicity and mechanisms between LMW-IR700 and Ab-IR700 targeting prostate-specific membrane antigen (PSMA). Both conjugates decreased cell viability to the same degree after light irradiation, but different morphological changes were observed in PSMA-positive LNCaP cells by microscopy. Cell swelling and bleb formation were induced by Ab-IR700, but only swelling was observed in cells treated with LMW-IR700, suggesting the cells were damaged via different cytotoxic mechanisms. However, LMW-IR700 induced bleb formation, a hallmark of NIR-PIT with Ab-IR700, when singlet oxygen was quenched or LMW-IR700 was localized only on the plasma membrane. Moreover, the water-soluble axial ligands of LMW-IR700 were cleaved, consistent with previous reports on Ab-IR700. Thus, the main cytotoxic mechanisms of Ab-IR700 and LMW-IR700 differ, although LMW-IR700 on the plasma membrane can cause aggregation-mediated cytotoxicity as well as Ab-IR700. - Photoimmunotherapy: A new cancer treatment using photochemical reactions.
Mikako Ogawa, Hideo Takakura
Bioorganic & medicinal chemistry, 43, 116274, 116274, 01 Aug. 2021, [International Magazine]
English, Scientific journal, Photoimmunotherapy (PIT) is a new molecular-targeted phototherapy in which administration of an antibody conjugated to IR700 (Ab-IR700, a phthalocyanine derivative) is followed by irradiation with near-infrared light. PIT induces cell death due to cell membrane damage, and the formation of IR700 aggregates on the cell membrane triggered by photochemical reactions is an important mechanism of cell killing. Specifically, water-soluble axial ligands of IR700 are cleaved by the photochemical reaction, and the phthalocyanine stacks up due to the π-π interaction, resulting in the formation of aggregates. In addition, the formation of IR700 radical anions and their protonation are essential for the progress of this photochemical reaction. The elucidation of these mechanisms may lead to the development of more effective compounds in the future. In addition, the optical properties of phthalocyanine are expected to expand the medical application of phthalocyanine derivatives in the future. - Transition-metal-free nucleophilic 211At-astatination of spirocyclic aryliodonium ylides.
Keitaro Matsuoka, Honoka Obata, Kotaro Nagatsu, Masahiro Kojima, Tatsuhiko Yoshino, Mikako Ogawa, Shigeki Matsunaga
Organic & biomolecular chemistry, 19, 25, 5525, 5528, 30 Jun. 2021, [International Magazine]
English, Scientific journal, The transition-metal-free 211At-astatination of spirocyclic aryliodonium ylides via a nucleophilic aromatic substitution reaction is described. This method enables the preparation of 211At-radiolabeled compounds derived from multi-functionalized molecules and heteroarenes in good to excellent radiochemical yields. - In Vitro and In Vivo Cell Uptake of a Cell-Penetrating Peptide Conjugated with Fluorescent Dyes Having Different Chemical Properties.
Hideo Takakura, Honoka Sato, Kohei Nakajima, Motofumi Suzuki, Mikako Ogawa
Cancers, 13, 9, 07 May 2021, [International Magazine]
English, Scientific journal, In molecular imaging, a targeting strategy with ligands is widely used because specificity can be significantly improved. In fluorescence imaging based on a targeting strategy, the fluorescent dyes conjugated with ligands may affect the targeting efficiency depending on the chemical properties. Herein, we used a cell-penetrating peptide (CPP) as a ligand with a variety of fluorescent cyanine dye. We investigated in vitro and in vivo cell uptake of the dye-CPP conjugates when cyanine dyes with differing charge and hydrophilicity/lipophilicity were used. The results showed that the conjugates with positively charged and lipophilic cyanine dyes accumulated in cancer cells in vitro, but there was almost no accumulation in tumors in vivo. On the other hand, the conjugates with negatively charged and hydrophilic cyanine dyes did not accumulate in cancer cells in vitro, but fluorescence was observed in tumors in vivo. These results show that there are some cases in which the cell uptake of the dye-peptide conjugates may differ significantly between in vitro and in vivo experiments due to the chemical properties of the fluorescent dyes. This suggests that attention should be paid to the chemical properties of fluorescent dyes in fluorescence imaging based on a targeting strategy. - PETイメージング剤を用いた動脈硬化病変におけるニコチン受容体の機能解明
鈴木 基史, 片山 竜樹, 鈴木 千恵, 中島 孝平, 間賀田 泰寛, 小川 美香子
JSMI Report, 14, 2, 125, 125, 日本分子イメージング学会, May 2021
Japanese - PETイメージング剤を用いた動脈硬化病変におけるニコチン受容体の機能解明
鈴木 基史, 片山 竜樹, 鈴木 千恵, 中島 孝平, 間賀田 泰寛, 小川 美香子
JSMI Report, 14, 2, 125, 125, 日本分子イメージング学会, May 2021
Japanese - In Vitro Evaluation of No-Carrier-Added Radiolabeled Cisplatin ([189, 191Pt]cisplatin) Emitting Auger Electrons.
Honoka Obata, Atsushi B Tsuji, Hitomi Sudo, Aya Sugyo, Katsuyuki Minegishi, Kotaro Nagatsu, Mikako Ogawa, Ming-Rong Zhang
International journal of molecular sciences, 22, 9, 28 Apr. 2021, [International Magazine]
English, Scientific journal, Due to their short-range (2-500 nm), Auger electrons (Auger e-) have the potential to induce nano-scale physiochemical damage to biomolecules. Although DNA is the primary target of Auger e-, it remains challenging to maximize the interaction between Auger e- and DNA. To assess the DNA-damaging effect of Auger e- released as close as possible to DNA without chemical damage, we radio-synthesized no-carrier-added (n.c.a.) [189, 191Pt]cisplatin and evaluated both its in vitro properties and DNA-damaging effect. Cellular uptake, intracellular distribution, and DNA binding were investigated, and DNA double-strand breaks (DSBs) were evaluated by immunofluorescence staining of γH2AX and gel electrophoresis of plasmid DNA. Approximately 20% of intracellular radio-Pt was in a nucleus, and about 2% of intra-nucleus radio-Pt bound to DNA, although uptake of n.c.a. radio-cisplatin was low (0.6% incubated dose after 25-h incubation), resulting in the frequency of cells with γH2AX foci was low (1%). Nevertheless, some cells treated with radio-cisplatin had γH2AX aggregates unlike non-radioactive cisplatin. These findings suggest n.c.a. radio-cisplatin binding to DNA causes severe DSBs by the release of Auger e- very close to DNA without chemical damage by carriers. Efficient radio-drug delivery to DNA is necessary for successful clinical application of Auger e-. - Synthesis of no-carrier-added [188, 189, 191Pt]cisplatin from a cyclotron produced 188, 189, 191PtCl42- complex.
Honoka Obata, Katsuyuki Minegishi, Kotaro Nagatsu, Mikako Ogawa, Ming-Rong Zhang
Scientific reports, 11, 1, 8140, 8140, 14 Apr. 2021, [International Magazine]
English, Scientific journal, We developed a novel method for production of no-carrier-added (n.c.a.) [188, 189, 191Pt]PtIICl42- from an Ir target material, and then synthesized n.c.a. [*Pt]cis-[PtIICl2(NH3)2] ([*Pt]cisplatin) from [*Pt]PtIICl42-. [*Pt]PtIICl42- was prepared as a synthetic precursor of n.c.a. *Pt complex by a combination of resin extraction and anion-exchange chromatography after the selective reduction of IrIVCl62- with ascorbic acid. The ligand-substitution reaction of Cl with NH3 was promoted by treating n.c.a. [*Pt]PtIICl42- with excess NH3 and heating the reaction mixture, and n.c.a. [*Pt]cisplatin was successfully produced without employing precipitation routes. After this treatment, [*Pt]cisplatin was isolated through preparative HPLC with a radiochemical purity of 99 + % at the end of synthesis (EOS). - Nothing seek, nothing find.-分子イメージングの先に見えるもの- 光音響イメージングのための機能性シアニン色素の開発
土屋 光輝, 高倉 栄男, 小川 美香子
日本薬学会年会要旨集, 141年会, GS05, 2, (公社)日本薬学会, Mar. 2021
Japanese - Nothing seek, nothing find.-分子イメージングの先に見えるもの- 光免疫療法における分子イメージングの利用
中島 孝平, 高倉 栄男, 小川 美香子
日本薬学会年会要旨集, 141年会, GS05, 3, (公社)日本薬学会, Mar. 2021
Japanese - Analysis of the triplet-state kinetics of a photosensitizer for photoimmunotherapy by fluorescence correlation spectroscopy
Hideo Takakura, Yuto Goto, Akira Kitamura, Toshitada Yoshihara, Seiji Tobita, Masataka Kinjo, Mikako Ogawa
Journal of Photochemistry and Photobiology A: Chemistry, 408, 01 Mar. 2021
Scientific journal - Near-infrared photoimmunotherapy (NIR-PIT) on cholangiocarcinoma using a novel catheter device with light emitting diodes.
Hajime Hirata, Masaki Kuwatani, Kohei Nakajima, Yuki Kodama, Yasuo Yoshikawa, Mikako Ogawa, Naoya Sakamoto
Cancer science, 112, 2, 828, 838, Feb. 2021, [International Magazine]
English, Scientific journal, Near-infrared photoimmunotherapy (NIR-PIT) is a novel therapy for cancers that uses NIR light and antibody-photosensitizer (IR700) conjugates. However, it is difficult to deliver NIR light into the bile duct for cholangiocarcinoma (CCA) from the conventional extracorporeal apparatus. Thus, in this study, we developed a dedicated catheter with light emitting diodes (LEDs) that supersedes conventional external irradiation devices; we investigated the therapeutic effect of NIR-PIT for CCA using the novel catheter. The new catheter was designed to be placed in the bile duct and a temperature sensor was attached to the tip of the catheter to avoid thermal burn. An anti-epidermal growth factor receptor (EGFR) antibody, Panitumumab-IR700 conjugate or anti-human epidermal growth factor receptor type 2 (HER2) antibody, Trastuzumab-IR700 conjugate, was used with EGFR- or HER2-expressing cell lines, respectively. The in vitro efficacy of NIR-PIT was confirmed in cultured cells; the capability of the new catheter for NIR-PIT was then tested in a mouse tumor model. NIR-PIT via the developed catheter treated CCA xenografts in mice. NIR-PIT had an effect in Panitumumab-IR700 conjugate- and Trastuzumab-IR700 conjugate-treated CCA cells that depended on the receptor expression level. Tumor growth was significantly suppressed in mice treated with NIR-PIT using the novel catheter compared with controls (P < .01). NIR-PIT was an effective treatment for EGFR- and HER2-expressing CCA cells, and the novel catheter with mounted LEDs was useful for NIR-PIT of CCA. - An imaging approach for determining the mechanism of enhancement of intestinal absorption of an L-theanine supplement.
Yuki Sato, Kazuki Yamaguchi, Mikako Ogawa, Yoh Takekuma, Mitsuru Sugawara
PloS one, 16, 6, e0253066, 2021, [International Magazine]
English, Scientific journal, BACKGROUND & OBJECTIVE: Theanine (L-glutamylethylamide) contained in green tea is a functional food component that has been attracting attention due to its relaxation effect. It was shown that the ingredients added to the theanine formulations increased the absorption of theanine. If this mechanism can be elucidated, it would be possible to contribute to development of evidence-based formulations. In this study, we investigated the effect of ingredients in the formulations on the absorption of theanine in detail. MAIN METHODS: After oral administration of a mixture of theanine and additional components to Wistar rats the plasma concentration was determined by an HPLC and the pharmacokinetic parameters were calculated. In addition, a new system for evaluating intestinal blood flow was developed since the involvement of intestinal blood flow was considered as a factor that increased absorption of theanine. KEY FINDINGS: Plasma concentration of theanine increased significantly in the combined use group with eight ingredients containing piperine as compared with theanine only group. Piperine would increase theanine absorption by increased blood flow, not an inhibition of metabolism. We succeeded to develop a visual and quantitative system to evaluate the effect of these ingredients directly including piperine on the intestinal blood flow using indocyanine green while maintaining physiological conditions. SIGNIFICANCE: Increased intestinal blood flow by these ingredients including piperine enhanced the absorption of theanine. Other mechanisms may also be considered as the mechanism by which theanine absorption is increased in addition to increased blood flow. - PETイメージング剤を用いた動脈硬化病変におけるニコチン受容体の機能解明
鈴木 基史, 片山 竜樹, 鈴木 千恵, 中島 孝平, 間賀田 泰寛, 小川 美香子
核医学, 57, Suppl., S149, S149, (一社)日本核医学会, Oct. 2020
Japanese - 免疫賦活マウス腫瘍における抗PD-1治療後の[18F]FDG取り込みに関する検討
富田 真由, 鈴木 基史, 河野 裕允, 中島 孝平, 松田 拓真, 久下 裕二, 小川 美香子
核医学, 57, Suppl., S150, S150, (一社)日本核医学会, Oct. 2020
Japanese - インテグリンαvβ3標的RGDペプチドを用いた光免疫療法のメカニズム解明
寺田 一貴, 中島 孝平, 高倉 栄男, 小川 美香子
日本癌学会総会記事, 79回, OJ16, 5, (一社)日本癌学会, Oct. 2020
English - Phototoxicity in near-infrared photoimmunotherapy is influenced by the subcellular localization of antibody-IR700.
Kohei Nakajima, Mikako Ogawa
Photodiagnosis and photodynamic therapy, 31, 101926, 101926, Sep. 2020, [International Magazine]
English, Scientific journal, BACKGROUND: Near-infrared photoimmunotherapy (NIR-PIT) is a newly developed cancer phototherapy that utilizes monoclonal antibody-IRDye700DX conjugates (mAb-IR700) and NIR light. We previously reported that mAb-IR700 aggregated on the plasma membrane and induced physical damage within the membrane, leading to necrotic/immunogenic cancer cell death. However, cytotoxic effects caused by internalized mAb-IR700, which is localized in lysosomes after endocytosis, remain unclear. Thus, in this study, we investigated how internalized mAb-IR700 influences phototoxicity. METHODS: Cytotoxicity depending on the subcellular localization of mAb-IR700 was examined by varying the incubation time after washing. The influence of a singlet oxygen (1O2) was examined by cell viability assay in the presence of 1O2 quencher. The type of cell death was analyzed by flow cytometry with Annexin V/propidium iodide. Furthermore, IR700 fluorescence in cells was observed by fluorescence microscopy. RESULTS: mAb-IR700 in lysosomes induced cytotoxicity, which was weaker than that induced by mAb-IR700 on plasma membranes. Cellular damage caused by mAb-IR700 in lysosomes was completely inhibited by an 1O2 quencher. mAb-IR700 on plasma membranes and in lysosomes induced necrotic, but not apoptotic, cell death. IR700 was localized in lysosomes before light irradiation but then diffused into the cytosol immediately after irradiation. CONCLUSIONS: Although the main cytotoxic trigger in NIR-PIT is plasma membrane damage as previously reported, mAb-IR700 in lysosomes also induces necrotic cell death. The internalized mAb-IR700 caused 1O2-mediated damage, leading to the marked leakage of lysosomal contents into the cytosol. The mechanism of NIR-PIT depends on the subcellular localization of mAb-IR700. - DDSとの融合による分子イメージングの新展開 標的化DDSの利用による動脈硬化巣の非侵襲的光イメージング
清水 広介, 成田 雄大, 浅井 知浩, 奥 直人, 小川 美香子, 間賀田 泰寛
日本DDS学会学術集会プログラム予稿集, 36回, 95, 95, 日本DDS学会, Aug. 2020
Japanese - 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, 30 Jun. 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, 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. - Theoretical and Experimental Studies on the Near‐Infrared Photoreaction Mechanism of a Silicon Phthalocyanine Photoimmunotherapy Dye: Photoinduced Hydrolysis by Radical Anion Generation
Masato Kobayashi, Mei Harada, Hideo Takakura, Kanta Ando, Yuto Goto, Takao Tsuneda, Mikako Ogawa, Tetsuya Taketsugu
ChemPlusChem, 85, 9, 1953, 1953, Wiley, 25 May 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, Invited for this month's cover are the collaborating groups of Dr. Masato Kobayashi and Prof. Mikako Ogawa, both from Hokkaido University, Sapporo, Japan. The cover picture shows the photochemical reaction process of the near-infrared (NIR) photoimmunotherapy dye IR700, and subsequent cancer cell death. A computational study predicted that ligand dissociation, which is known to initiate cancer cell death, proceeds by the hydrolysis of the IR700 radical anion, rather than as a direct result of NIR irradiation. This mechanism has also been supported by experimental work. Read the full text of the Communication at 10.1002/cplu.202000338. - Potential role of transforming growth factor-beta 1/Smad signaling in secondary lymphedema after cancer surgery.
Masaki Sano, Satoshi Hirakawa, Minoru Suzuki, Jun-Ichi Sakabe, Mikako Ogawa, Seiji Yamamoto, Takanori Hiraide, Takeshi Sasaki, Naoto Yamamoto, Kazunori Inuzuka, Hiroki Tanaka, Takaaki Saito, Ryota Sugisawa, Kazuto Katahashi, Tatsuro Yata, Takafumi Kayama, Tetsumei Urano, Yoshiki Tokura, Kohji Sato, Mitsutoshi Setou, Hiroya Takeuchi, Hiroyuki Konno, Naoki Unno
Cancer science, 111, 7, 2620, 2634, 15 May 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, Secondary lymphedema often develops after cancer surgery, and over 250 million patients suffer from this complication. A major symptom of secondary lymphedema is swelling with fibrosis, which lowers the patient's quality of life, even if cancer does not recur. Nonetheless, the pathophysiology of secondary lymphedema remains unclear, with therapeutic approaches limited to physical or surgical therapy. There is no effective pharmacological therapy for secondary lymphedema. Notably, the lack of animal models that accurately mimic human secondary lymphedema has hindered pathophysiological investigations of the disease. Here, we developed a novel rat hindlimb model of secondary lymphedema and showed that our rat model mimics human secondary lymphedema from early to late stages in terms of cell proliferation, lymphatic fluid accumulation, and skin fibrosis. Using our animal model, we investigated the disease progression and found that transforming growth factor-beta 1 (TGFB1) was produced by macrophages in the acute phase and by fibroblasts in the chronic phase of the disease. TGFB1 promoted the transition of fibroblasts into myofibroblasts and accelerated collagen synthesis, resulting in fibrosis, which further indicates that myofibroblasts and TGFB1/Smad signaling play key roles in fibrotic diseases. Furthermore, the presence of myofibroblasts in skin samples from lymphedema patients after cancer surgery emphasizes the role of these cells in promoting fibrosis. Suppression of myofibroblast-dependent TGFB1 production may therefore represent an effective pharmacological treatment for inhibiting skin fibrosis in human secondary lymphedema after cancer surgery. - 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, 19 Mar. 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, 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. - PSMAを標的とする小分子リガンドを利用した新規光免疫療法薬剤の開発
宮崎 風香, 中島 孝平, 寺田 一貴, 高倉 栄男, 小川 美香子
日本薬学会年会要旨集, 140年会, 28M, pm03S, (公社)日本薬学会, Mar. 2020
Japanese - Theoretical and Experimental Studies on the Near-Infrared Photoreaction Mechanism of a Silicon Phthalocyanine Photoimmunotherapy Dye: Photoinduced Hydrolysis by Radical Anion Generation
Masato Kobayashi, Mei Harada, Hideo Takakura, Kanta Ando, Yuto Goto, Takao Tsuneda, Mikako Ogawa, Tetsuya Taketsugu
ChemPlusChem, Wiley-VCH Verlag, 2020
English, Scientific journal - Surface Modification of Liposomes Using IR700 Enables Efficient Controlled Contents Release Triggered by Near-IR Light.
Yusuke Kono, Kazuha Yokoyama, Motofumi Suzuki, Hideo Takakura, Mikako Ogawa
Biological & pharmaceutical bulletin, 43, 4, 736, 741, 2020, [Peer-reviewed], [Domestic magazines]
English, Scientific journal, Stimuli-responsive liposomes are promising drug carriers for cancer treatment because they enable controlled drug release and the maintenance of desired drug concentrations in tumor tissue. In particular, near-IR (NIR) light is a useful stimulus for triggering drug release from liposomes based on its advantages such as deep tissue penetration and safety. Previously, we found that a silicon phthalocyanine derivative, IR700, conjugated to antibodies, can induce the rupture of the cell membrane following irradiation by NIR light. Based on this finding, we constructed IR700-modified liposomes (IR700 liposomes) and evaluated their drug release properties triggered by NIR light. IR700 liposomes released substantial amounts of encapsulated calcein following irradiation by NIR light. Drug release was substantially suppressed by the addition of sodium azide, suggesting that liposomal membrane permeabilization was mediated by singlet oxygen generated from IR700. Moreover, calcein release from IR700 liposomes triggered by NIR light was promoted under conditions of deoxygenation and the presence of electron donors. Thus, membrane disruption should be induced by the physical change of IR700 from highly hydrophilic to hydrophobic as we previously described, although singlet oxygen can cause a certain level of membrane disruption under normoxia. We also observed that doxorubicin-encapsulated IR700 liposomes exhibited significant cytotoxic effects against CT-26 murine colon carcinoma cells following NIR light exposure. These results indicate that IR700 liposomes can efficiently release anti-cancer drugs following NIR light irradiation even under hypoxic conditions and, therefore, they would be useful for cancer treatment. - From the respective expert viewpoints of the ANM specialty editors.
Masayuki Inubushi, Miho Shidahara, Yasuyuki Takahashi, Mikako Ogawa, Yasushi Kiyono
Annals of nuclear medicine, 33, 12, 877, 880, Dec. 2019, [Domestic magazines]
English, Scientific journal, Although it may not be well known, the Annals of Nuclear Medicine (ANM) Editorial Committee includes one specialty editor of nuclear medicine physics, one of nuclear medicine technology, one of molecular imaging, and two of radiopharmacology. In addition, a statistics editor and a language editor are also on the committee. Manuscripts submitted to ANM can be peer-reviewed by such specialty editors similar to those submitted to highly ranked journals, which is a great pride and joy to us. To offer our readers a condensed global view on the high-quality research work in the field of nuclear medicine, we have published a mini-review article every year under the joint authorship of the ANM associate editors since 2016. This is our fourth serial review article written by the ANM specialty editors from their respective expert viewpoints. - 深部がんを検出可能なpH応答性光音響イメージング剤の開発(pH-activatable photoacoustic imaging agents for detecting deep tumors)
土屋 光輝, 高倉 栄男, 小川 美香子
日本癌学会総会記事, 78回, J, 1047, (一社)日本癌学会, Sep. 2019
English - 光免疫療法が腫瘍に及ぼす変化に関する[18F]FDGと[18F]FMISOを用いた検討(Evaluation of changes in biological characteristics after photoimmunotherapy using [18F]FDG and [18F]FMISO)
中島 孝平, 安井 博宣, 東川 桂, 高倉 栄男, 久下 裕司, 小川 美香子
日本癌学会総会記事, 78回, P, 3146, (一社)日本癌学会, Sep. 2019
English - 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
Annals of nuclear medicine, 33, 5, 362, 367, May 2019, [Peer-reviewed], [Domestic magazines]
English, Scientific journal, 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. - Macrophage-targeted, enzyme-triggered fluorescence switch-on system for detection of embolism-vulnerable atherosclerotic plaques.
Narita Y, Shimizu K, Ikemoto K, Uchino R, Kosugi M, Maess MB, Magata Y, Oku N, Ogawa M
Journal of controlled release : official journal of the Controlled Release Society, 302, 105, 115, May 2019, [Peer-reviewed], [International Magazine]
English, Scientific journal, The development of atherosclerotic plaques is a critical step that can result in an arterial embolism. Therefore, detection of these vulnerable plaques is of clinical significance for the diagnosis of atherosclerosis. However, there are few imaging systems able to detect such plaques easily. In this study, we designed a new platform for near-infrared fluorescence (NIRF) imaging of macrophages in atherosclerotic plaques, one using both a liposomal DDS and an activatable fluorescent probe, and evaluated the utility of this imaging for the diagnosis of atherosclerosis. We first synthesized a fluorescent switch-on probe, Peptide-ICG2, which is optically silent under normal conditions but activated in the presence of the lysosomal enzyme, cathepsin B. To achieve macrophage-specific fluorescence activation, we encapsulated Peptide-ICG2 into phosphatidylserine-containing liposome (P-ICG2-PS-Lip), since the accumulation of phosphatidylserine receptor-bearing macrophages is characteristic of embolism-vulnerable plaques. The experiments using macrophage-like RAW264 cells in culture showed that P-ICG2-PS-Lip was selectively taken up into the cells and that significant fluorescence of the probe was observed. For NIRF imaging of the atherosclerotic plaques, P-ICG2-PS-Lip was intravenously injected into ApoE-knockout atherosclerotic model mice or WHHL rabbits, and the fluorescence at the aortae was imaged. The results indicated that ICG fluorescence could be successfully observed at the plaques on the artery walls. The results of the present study thus suggest that NIRF imaging using P-ICG2-PS-Lip would be useful for detecting embolism-vulnerable atherosclerotic plaques. - 小分子ペプチドを利用した光免疫療法のメカニズム解明
寺田 一貴, 中島 孝平, 高倉 栄男, 小川 美香子
JSMI Report, 12, 2, 118, 118, 日本分子イメージング学会, May 2019
Japanese - 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
JSMI Report, 12, 2, 131, 131, 日本分子イメージング学会, May 2019
Japanese - 量子化学計算を用いた光免疫療法における細胞障害メカニズムの検討
原田 芽生, 小林 正人, 安藤 完太, 高倉 栄男, 武次 徹也, 小川 美香子
日本薬学会年会要旨集, 139年会, 2, 80, 80, (公社)日本薬学会, Mar. 2019
Japanese - 光免疫療法の細胞障害メカニズム
小川 美香子, 佐藤 和秀, 安藤 完太, 奥山 修平, 森口 志穂, 小倉 泰郎, 十時 慎一郎, 花岡 宏史, 長屋 匡信, 粉川 良平, 高倉 栄男, 西村 雅之, 長谷川 好規, Choyke Peter, 小林 久隆
日本薬学会年会要旨集, 139年会, 2, 80, 80, (公社)日本薬学会, Mar. 2019
Japanese - A Novel PET Probe "[18F]DiFA" Accumulates in Hypoxic Region via Glutathione Conjugation Following Reductive Metabolism.
Yoichi Shimizu, Songji Zhao, Hironobu Yasui, Ken-Ichi Nishijima, Hiroki Matsumoto, Tohru Shiga, Nagara Tamaki, Mikako Ogawa, Yuji Kuge
Molecular imaging and biology, 21, 1, 122, 129, Feb. 2019, [Peer-reviewed], [International Magazine]
English, Scientific journal, 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. - Photoinduced Ligand Release from a Silicon Phthalocyanine Dye Conjugated with Monoclonal Antibodies: A Mechanism of Cancer Cell Cytotoxicity after Near-Infrared Photoimmunotherapy.
Sato K, Ando K, Okuyama S, Moriguchi S, Ogura T, Totoki S, Hanaoka H, Nagaya T, Kokawa R, Takakura H, Nishimura M, Hasegawa Y, Choyke PL, Ogawa M, Kobayashi H
ACS central science, 4, 11, 1559, 1569, Nov. 2018, [Peer-reviewed], [International Magazine]
English, Scientific journal, Photochemical reactions can dramatically alter physical characteristics of reacted molecules. In this study, we demonstrate that near-infrared (NIR) light induces an axial ligand-releasing reaction, which dramatically alters hydrophilicity of a silicon phthalocyanine derivative (IR700) dye leading to a change in the shape of the conjugate and its propensity to aggregate in aqueous solution. This photochemical reaction is proposed as a major mechanism of cell death induced by NIR photoimmunotherapy (NIR-PIT), which was recently developed as a molecularly targeted cancer therapy. Once the antibody-IR700 conjugate is bound to its target, activation by NIR light causes physical changes in the shape of antibody antigen complexes that are thought to induce physical stress within the cellular membrane leading to increases in transmembrane water flow that eventually lead to cell bursting and necrotic cell death. - PD-1治療が[18F]FDGのがん組織への集積に与える影響についてのマウスを用いた検討
富田 真由, 安井 博宣, 東川 桂, 中島 孝平, 高倉 栄男, 志賀 哲, 久下 裕司, 小川 美香子
核医学, 55, Suppl., S173, S173, (一社)日本核医学会, Nov. 2018
English - 光免疫療法による[18F]FDGおよび[18F]FMISOの集積変化に関する検討
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
核医学, 55, Suppl., S174, S174, (一社)日本核医学会, Nov. 2018
English - 小分子ペプチドをリガンドとして用いた光免疫療法新規治療薬の開発(Development of a new therapeutic agent for photoimmunotherapy with small peptides as a targeting ligand)
寺田 一貴, 高倉 栄男, 中島 孝平, 小川 美香子
日本癌学会総会記事, 77回, 132, 132, (一社)日本癌学会, Sep. 2018
English - 深部腫瘍の治療を可能とするワイヤレス給電LEDを用いた光免疫療法(Near-infrared photoimmunotherapy(NIR-PIT) using wireless light-emitting diode system to treat tumors in deep tissue)
中島 孝平, 高倉 栄男, 小川 美香子
日本癌学会総会記事, 77回, 133, 133, (一社)日本癌学会, Sep. 2018
English - Evaluation of drug effects on cerebral blood flow and glucose uptake in un-anesthetized and un-stimulated rats: application of free-moving apparatus enabling to keep rats free during PET/SPECT tracer injection and uptake.
Sugita T, Kondo Y, Ishino S, Mori I, Horiguchi T, Ogawa M, Magata Y
Nuclear medicine communications, 39, 8, 753, 760, Aug. 2018, [Peer-reviewed] - 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 research, 8, 1, 82, Springer Science and Business Media LLC, Aug. 2018, [Peer-reviewed]
Scientific journal - Changes in plasma membrane damage inducing cell death after treatment with near-infrared photoimmunotherapy.
Nakajima K, Takakura H, Shimizu Y, Ogawa M
Cancer science, 109, 9, 2889, 2896, Wiley, Jun. 2018, [Peer-reviewed]
Scientific journal - 近赤外光線免疫療法への利用を目指した埋め込み型ワイヤレス給電LEDの開発
中島 孝平, 木村 俊広, 高倉 栄男, 吉川 恭央, 亀田 篤志, 進藤 崇之, 佐藤 和秀, 小林 久隆, 小川 美香子
JSMI Report, 11, 2, 96, 96, 日本分子イメージング学会, May 2018
Japanese - 小分子ペプチドを利用した新規光線免疫療法薬剤の開発
寺田 一貴, 高倉 栄男, 中島 孝平, 安藤 完太, 小川 美香子
JSMI Report, 11, 2, 139, 139, 日本分子イメージング学会, May 2018
Japanese - 薬剤の構造変化に着目した光線免疫療法のメカニズム解明
高倉 栄男, 安藤 完太, 中島 孝平, 小川 美香子
JSMI Report, 11, 2, 75, 75, 日本分子イメージング学会, May 2018
Japanese - Implantable wireless powered light emitting diode (LED) for near-infrared photoimmunotherapy: Device development and experimental assessment in vitro and in vivo
Kohei Nakajima, Toshihiro Kimura, Hideo Takakura, Yasuo Yoshikawa, Atsushi Kameda, Takayuki Shindo, Kazuhide Sato, Hisataka Kobayashi, Mikako Ogawa
Oncotarget, 9, 28, 20048, 20057, Impact Journals LLC, 13 Apr. 2018, [Peer-reviewed]
English, Scientific journal - [18F]FDG PETを用いたPD-1治療効果の早期予測に関するin vivoでの検討
富田 真由, 高倉 栄男, 安井 博宣, 東川 桂, 久下 裕司, 小川 美香子
日本薬学会年会要旨集, 138年会, 4, 66, 66, (公社)日本薬学会, Mar. 2018
Japanese - 光線免疫療法におけるメカニズム解明に向けた薬剤の光応答性に関する検討
安藤 完太, 中島 孝平, 高倉 栄男, 小川 美香子
日本薬学会年会要旨集, 138年会, 4, 66, 66, (公社)日本薬学会, Mar. 2018
Japanese - 光線免疫療法によるがん細胞死誘発過程における細胞膜の変化に関する検討
中島 孝平, 高倉 栄男, 志水 陽一, 浅沼 大祐, 上野 匡, 浦野 泰照, 小川 美香子
日本薬学会年会要旨集, 138年会, 4, 66, 66, (公社)日本薬学会, Mar. 2018
Japanese - In vivo molecular imaging for biomedical analysis and therapies
Mikako Ogawa, Hideo Takakura
Analytical Sciences, 34, 3, 273, 281, Japan Society for Analytical Chemistry, 2018, [Peer-reviewed]
English - 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, Aug. 2017, [Peer-reviewed]
English, Scientific journal - Immunogenic cancer cell death selectively induced by near infrared photoimmunotherapy initiates host tumor immunity
Mikako Ogawa, Yusuke Tomita, Yuko Nakamura, Min-Jung Lee, Sunmin Lee, Saori Tomita, Tadanobu Nagaya, Kazuhide Sato, Toyohiko Yamauchi, Hidenao Iwai, Abhishek Kumar, Timothy Haystead, Hari Shroff, Peter L. Choyke, Jane B. Trepel, Hisataka Kobayashi
ONCOTARGET, 8, 6, 10425, 10436, Feb. 2017, [Peer-reviewed]
English, Scientific journal - Peptide-based tumor inhibitor encoding mitochondrial p14(ARF) is highly efficacious to diverse tumors
Ken Saito, Hidekazu Iioka, Chie Kojima, Mikako Ogawa, Eisaku Kondo
CANCER SCIENCE, 107, 9, 1290, 1301, Sep. 2016, [Peer-reviewed]
English, Scientific journal - Monoclonal antibody-based optical molecular imaging probes; considerations and caveats in chemistry, biology and pharmacology
Hisataka Kobayashi, Peter L. Choyke, Mikako Ogawa
CURRENT OPINION IN CHEMICAL BIOLOGY, 33, 32, 38, Aug. 2016, [Peer-reviewed]
English - 病態メカニズムに迫るイメージング技術 DDSへの期待 動脈硬化のマルチモダル生体イメージングを目指したDDS製剤の開発
小川 美香子, 清水 広介, 成田 雄大, Maess Marten, 梅田 泉, 奥 直人, 間賀田 泰寛
日本DDS学会学術集会プログラム予稿集, 32回, 95, 95, 日本DDS学会, Jun. 2016
Japanese - Optimization of dendrimer structure for sentinel lymph node imaging: Effects of generation and terminal group
Yuichiro Niki, Mikako Ogawa, Rie Makiura, Yasuhiro Magata, Chie Kojima
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE, 11, 8, 2119, 2127, Nov. 2015, [Peer-reviewed]
English, Scientific journal - A handy camera for near-infrared fluorescence imaging
Mikako Ogawa
Drug Delivery System, 30, 2, 145, 148, Japan Society of Drug Delivery System, 25 Jun. 2015, [Peer-reviewed]
Japanese, Scientific journal - Radiosynthesis and in vivo evaluation of two imidazopyridineacetamides, [C-11]CB184 and [C-11]CB190, as a PET tracer for 18 kDa translocator protein: direct comparison with [C-11](R)-PK11195
Kentaro Hatano, Katsuhiko Sekimata, Takashi Yamada, Junichiro Abe, Kengo Ito, Mikako Ogawa, Yasuhiro Magata, Jun Toyohara, Kiichi Ishiwata, Giovanni Biggio, Mariangela Serra, Valentino Laquintana, Nunzio Denora, Andrea Latrofa, Giuseppe Trapani, Gaetano Liso, Hiromi Suzuki, Makoto Sawada, Masahiko Nomura, Hiroshi Toyama
ANNALS OF NUCLEAR MEDICINE, 29, 4, 325, 335, May 2015, [Peer-reviewed]
English, Scientific journal - Development of radioiodinated lipophilic cationic compounds for myocardial imaging
Toshihiro Sakai, Yuriko Saito, Misato Takashima, Mikako Ogawa, Yasuhiro Magata
NUCLEAR MEDICINE AND BIOLOGY, 42, 5, 482, 487, May 2015, [Peer-reviewed]
English, Scientific journal - PEG modification on In-111-labeled phosphatidyl serine liposomes for imaging of atherosclerotic plaques
Mikako Ogawa, Ryuji Uchino, Ayumi Kawai, Mutsumi Kosugi, Yasuhiro Magata
NUCLEAR MEDICINE AND BIOLOGY, 42, 3, 299, 304, Mar. 2015, [Peer-reviewed]
English, Scientific journal - Sensitive beta-galactosidase-targeting fluorescence probe for visualizing small peritoneal metastatic tumours in vivo
Daisuke Asanuma, Masayo Sakabe, Mako Kamiya, Kyoko Yamamoto, Jun Hiratake, Mikako Ogawa, Nobuyuki Kosaka, Peter L. Choyke, Tetsuo Nagano, Hisataka Kobayashi, Yasuteru Urano
NATURE COMMUNICATIONS, 6, 6463, Mar. 2015, [Peer-reviewed]
English, Scientific journal - Prolonged local retention of subcutaneously injected polymers monitored by noninvasive SPECT imaging
Chie Kojima, Yuichiro Niki, Mikako Ogawa, Yasuhiro Magata
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 476, 1-2, 164, 168, Dec. 2014, [Peer-reviewed]
English, Scientific journal - Radiolabeled gamma-polyglutamic acid complex as a nano-platform for sentinel lymph node imaging
Kohei Sano, Yuriko Iwamiya, Tomoaki Kurosaki, Mikako Ogawa, Yasuhiro Magata, Hitoshi Sasaki, Takashi Ohshima, Minoru Maeda, Takahiro Mukai
JOURNAL OF CONTROLLED RELEASE, 194, 310, 315, Nov. 2014, [Peer-reviewed]
English, Scientific journal - Application of nano-particles for in vivo molecular imaging
Mikako Ogawa
Transactions of Japanese Society for Medical and Biological Engineering, 52, 35, SY-36, Japan Soc. of Med. Electronics and Biol. Engineering, 17 Aug. 2014, [Peer-reviewed]
English, Scientific journal - In vivo molecular imaging techniques for non-invasive atherosclerotic plaque detection
Mikako Ogawa, Kosuke Shimizu, Huijun Zhu, Yasuhiro Magata, Naoto Oku
Transactions of Japanese Society for Medical and Biological Engineering, 52, 60, SY-61, Japan Soc. of Med. Electronics and Biol. Engineering, 17 Aug. 2014, [Peer-reviewed]
English, Scientific journal - 動脈硬化不安定プラークイメージングのためのリポソーム製剤の開発
小川 美香子, 内納 隆治, 梅田 泉, 間賀田 泰寛
日本動脈硬化学会総会プログラム・抄録集, 46回, 220, 220, (一社)日本動脈硬化学会, Jun. 2014
Japanese - 動脈硬化不安定プラークマルチモダルイメージングのためのリポソーム製剤の開発
小川 美香子, 内納 隆治, 梅田 泉, 間賀田 泰寛
JSMI Report, 7, 2, 79, 79, 日本分子イメージング学会, May 2014
Japanese - F-18-FDG PET and intravascular ultrasonography (IVUS) images compared with histology of atherosclerotic plaques: F-18-FDG accumulates in foamy macrophages
Seigo Ishino, Mikako Ogawa, Ikuo Mori, Satoshi Nishimura, Shota Ikeda, Taku Sugita, Tatsuo Oikawa, Takashi Horiguchi, Yasuhiro Magata
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, 41, 4, 624, 633, Apr. 2014, [Peer-reviewed]
English, Scientific journal - MRI-蛍光デュアルイメージングプローブ2BDP3Gdによる動脈硬化巣の可視化
岩木 慎平, 花岡 健二郎, 外村 和也, 小川 美香子, 竹原 康雄, 萩沢 康介, 守本 祐司, 梅村 和夫, 長野 哲雄, 浦野 泰照
日本薬学会年会要旨集, 134年会, 2, 300, 300, (公社)日本薬学会, Mar. 2014
Japanese - Dendrimers as high relaxivity MR contrast agents
Michelle R. Longmire, Mikako Ogawa, Peter L. Choyke, Hisataka Kobayashi
WILEY INTERDISCIPLINARY REVIEWS-NANOMEDICINE AND NANOBIOTECHNOLOGY, 6, 2, 155, 162, Mar. 2014, [Peer-reviewed]
English - Lymphangiogenesis and Angiogenesis in Abdominal Aortic Aneurysm
Masaki Sano, Takeshi Sasaki, Satoshi Hirakawa, Junichi Sakabe, Mikako Ogawa, Satoshi Baba, Nobuhiro Zaima, Hiroki Tanaka, Kazunori Inuzuka, Naoto Yamamoto, Mitsutoshi Setou, Kohji Sato, Hiroyuki Konno, Naoki Unno
PLOS ONE, 9, 3, e89830, Mar. 2014, [Peer-reviewed]
English, Scientific journal - Investigation of dynamic morphological changes of cancer cells during photoimmuno therapy (PIT) by low-coherence quantitative phase microscopy
Mikako Ogawa, Toyohiko Yamauchi, Hidenao Iwai, Yasuhiro Magata, Peter L. Choyke, Hisataka Kobayashi
Progress in Biomedical Optics and Imaging - Proceedings of SPIE, 8931, SPIE, 2014, [Peer-reviewed]
English, International conference proceedings - Investigation of dynamic morphological changes of cancer cells during photoimmuno therapy (PIT) by low-coherence quantitative phase microscopy
Mikako Ogawa, Toyohiko Yamauchi, Hidenao Iwai, Yasuhiro Magata, Peter L. Choyke, Hisataka Kobayashi
OPTICAL METHODS FOR TUMOR TREATMENT AND DETECTION: MECHANISMS AND TECHNIQUES IN PHOTODYNAMIC THERAPY XXIII, 8931, 2014, [Peer-reviewed]
English, International conference proceedings - Development of In-111-Labeled Liposomes for Vulnerable Atherosclerotic Plaque Imaging
Mikako Ogawa, Izumi O. Umeda, Mutsumi Kosugi, Ayumi Kawai, Yuka Hamaya, Misato Takashima, Hongxia Yin, Takayuki Kudoh, Masaharu Seno, Yasuhiro Magata
JOURNAL OF NUCLEAR MEDICINE, 55, 1, 115, 120, Jan. 2014, [Peer-reviewed]
English, Scientific journal - Relationship between uptake of a radioiodinated quinazoline derivative and radiosensitivity in non-small cell lung cancer.
Zhu HJ, Ogawa M, Magata Y, Hirata M, Ohmomo Y, Sakahara H
American journal of nuclear medicine and molecular imaging, 4, 4, 293, 302, 2014, [Peer-reviewed] - A design strategy for small molecule-based targeted MRI contrast agents: their application for detection of atherosclerotic plaques
Shimpei Iwaki, Kazuya Hokamura, Mikako Ogawa, Yasuo Takehara, Yasuaki Muramatsu, Takehiro Yamane, Kazuhisa Hirabayashi, Yuji Morimoto, Kohsuke Hagisawa, Kazuhide Nakahara, Tomoko Mineno, Takuya Terai, Toru Komatsu, Tasuku Ueno, Keita Tamura, Yusuke Adachi, Yasunobu Hirata, Makoto Arita, Hiroyuki Arai, Kazuo Umemura, Tetsuo Nagano, Kenjiro Hanaoka
ORGANIC & BIOMOLECULAR CHEMISTRY, 12, 43, 8611, 8618, 2014, [Peer-reviewed]
English, Scientific journal - Accumulated phosphatidylcholine (16:0/16:1) in human colorectal cancer; possible involvement of LPCAT4
Nobuya Kurabe, Takahiro Hayasaka, Mikako Ogawa, Noritaka Masaki, Yoshimi Ide, Michihiko Waki, Toshio Nakamura, Kiyotaka Kurachi, Tomoaki Kahyo, Kazuya Shinmura, Yutaka Midorikawa, Yasuyuki Sugiyama, Mitsutoshi Setou, Haruhiko Sugimura
CANCER SCIENCE, 104, 10, 1295, 1302, Oct. 2013, [Peer-reviewed]
English, Scientific journal - Accumulated phosphatidylcholine (16:0/16:1) in human colorectal cancer; possible involvement of LPCAT4
Nobuya Kurabe, Takahiro Hayasaka, Mikako Ogawa, Noritaka Masaki, Yoshimi Ide, Michihiko Waki, Toshio Nakamura, Kiyotaka Kurachi, Tomoaki Kahyo, Kazuya Shinmura, Yutaka Midorikawa, Yasuyuki Sugiyama, Mitsutoshi Setou, Haruhiko Sugimura
Cancer Science, 104, 10, 1295, 1302, Oct. 2013, [Peer-reviewed]
English, Scientific journal - Alterations in alpha 4 beta 2 nicotinic receptors in cognitive decline in Alzheimer's aetiopathology
Hiroyuki Okada, Yasuomi Ouchi, Mikako Ogawa, Masami Futatsubashi, Yuriko Saito, Etsuji Yoshikawa, Tatsuhiro Terada, Yumi Oboshi, Hideo Tsukada, Takatoshi Ueki, Mitsuo Watanabe, Takaji Yamashita, Yasuhiro Magata
BRAIN, 136, Pt 10, 3004, 3017, Oct. 2013, [Peer-reviewed]
English, Scientific journal - 動脈硬化不安定プラークイメージングのためのリポソーム製剤の開発
小川 美香子, 内納 隆治, 梅田 泉, 間賀田 泰寛
核医学, 50, 3, S188, S188, (一社)日本核医学会, Sep. 2013
Japanese - Differentiation of tumor sensitivity to photodynamic therapy and early evaluation of treatment effect by nuclear medicine techniques
Jie Liu, Mikako Ogawa, Toshihiro Sakai, Misato Takashima, Shigetoshi Okazaki, Yasuhiro Magata
ANNALS OF NUCLEAR MEDICINE, 27, 7, 669, 675, Aug. 2013, [Peer-reviewed]
English, Scientific journal - Comparison of Contrast Agents for Atherosclerosis Imaging Using Cultured Macrophages: FDG Versus Ultrasmall Superparamagnetic Iron Oxide
Tomoko Satomi, Mikako Ogawa, Ikuo Mori, Seigo Ishino, Kazuki Kubo, Yasuhiro Magata, Tomoyuki Nishimoto
JOURNAL OF NUCLEAR MEDICINE, 54, 6, 999, 1004, Jun. 2013, [Peer-reviewed]
English, Scientific journal - 動脈硬化巣の可視化を目指したMRI造影剤の開発とその応用
岩木 慎平, 外村 和也, 小川 美香子, 竹原 康雄, 梅村 和夫, 長野 哲雄, 花岡 健二郎
JSMI Report, 6, 2, 121, 121, 日本分子イメージング学会, May 2013
Japanese - 浜松医科大学イメージングコンプレックスの形成 第三世代PET施設の構築
間賀田 泰寛, 小川 美香子, 高島 好聖, 外村 和也, 竹原 康雄, 夏目 貴弘, 阿部 紀里子, 小野寺 雄一郎, 尾内 康臣, 阪原 晴海, 梅村 和夫, 山本 清二
JSMI Report, 6, 2, 114, 114, 日本分子イメージング学会, May 2013, [Peer-reviewed]
Japanese - 動脈硬化の可視化を目指したMRIプローブの開発とその応用
岩木 慎平, 花岡 健二郎, 外村 和也, 小川 美香子, 竹原 康雄, 梅村 和夫, 長野 哲雄
日本薬学会年会要旨集, 133年会, 2, 311, 311, (公社)日本薬学会, Mar. 2013
Japanese - Doxorubicin-conjugated dendrimer/collagen hybrid gels for metastasis-associated drug delivery systems
Chie Kojima, Tomoyuki Suehiro, Kenji Watanabe, Mikako Ogawa, Ayano Fukuhara, Eiko Nishisaka, Atsushi Harada, Kenji Kono, Takashi Inui, Yasuhiro Magata
ACTA BIOMATERIALIA, 9, 3, 5673, 5680, Mar. 2013, [Peer-reviewed]
English, Scientific journal - One-pot sequential reactions for the synthesis of versatile C-11-labeled olefin frameworks
Misato Takashima, Koichi Kato, Mikako Ogawa, Yasuhiro Magata
RSC ADVANCES, 3, 44, 21275, 21279, 2013, [Peer-reviewed]
English, Scientific journal - Assessment of epidermal growth factor receptor status in glioblastomas.
Zhu HJ, Ogawa M, Magata Y, Hirata M, Ohmomo Y, Namba H, Sakahara H
Asia Oceania journal of nuclear medicine & biology, 1, 2, 47, 52, 2013, [Peer-reviewed] - 動脈硬化不安定プラークのイメージングを目的とした、111In標識リポソームの開発
小川 美香子, 梅田 泉, 小杉 睦, 河合 亜由美, 間賀田 泰寛
核医学, 49, 3, S248, S248, (一社)日本核医学会, Aug. 2012
Japanese - Sentinel lymph node imaging with a novel radiolabeled gamma-polyglutamic acid complex
Sano Kohei, Iwamiya Yuriko, Kurosaki Tomoaki, Ogawa Mikako, Magata Yasuhiro, Sasaki Hitoshi, Ohshima Takashi, Maeda Minoru, Mukai Takahiro
JOURNAL OF NUCLEAR MEDICINE, 53, 01 May 2012, [Peer-reviewed]
English - What Can Be Seen by F-18-FDG PET in Atherosclerosis Imaging? The Effect of Foam Cell Formation on F-18-FDG Uptake to Macrophages In Vitro
Mikako Ogawa, Satoki Nakamura, Yuriko Saito, Mutsumi Kosugi, Yasuhiro Magata
JOURNAL OF NUCLEAR MEDICINE, 53, 1, 55, 58, Jan. 2012, [Peer-reviewed]
English, Scientific journal - Dendrimer-based MRI contrast agents: the effects of PEGylation on relaxivity and pharmacokinetics
Chie Kojima, Baris Turkbey, Mikako Ogawa, Marcelino Bernardo, Celeste A. S. Regino, L. Henry Bryant, Peter L. Choyke, Kenji Kono, Hisataka Kobayashi
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE, 7, 6, 1001, 1008, Dec. 2011, [Peer-reviewed]
English, Scientific journal - Cancer cell-selective in vivo near infrared photoimmunotherapy targeting specific membrane molecules
Makoto Mitsunaga, Mikako Ogawa, Nobuyuki Kosaka, Lauren T. Rosenblum, Peter L. Choyke, Hisataka Kobayashi
NATURE MEDICINE, 17, 12, 1685, U210, Dec. 2011, [Peer-reviewed]
English, Scientific journal - Rapid Cancer Detection by Topically Spraying a gamma-Glutamyltranspeptidase-Activated Fluorescent Probe
Yasuteru Urano, Masayo Sakabe, Nobuyuki Kosaka, Mikako Ogawa, Makoto Mitsunaga, Daisuke Asanuma, Mako Kamiya, Matthew R. Young, Tetsuo Nagano, Peter L. Choyke, Hisataka Kobayashi
SCIENCE TRANSLATIONAL MEDICINE, 3, 110, 110ra119, Nov. 2011, [Peer-reviewed]
English, Scientific journal - Biologically Optimized Nanosized Molecules and Particles: More than Just Size
Michelle R. Longmire, Mikako Ogawa, Peter L. Choyke, Hisataka Kobayashi
BIOCONJUGATE CHEMISTRY, 22, 6, 993, 1000, Jun. 2011, [Peer-reviewed]
English - In Vivo Relationship Between Thalamic Nicotinic Acetylcholine Receptor Occupancy Rates and Antiallodynic Effects in a Rat Model of Neuropathic Pain: Persistent Agonist Binding Inhibits the Expression of Antiallodynic Effects
Masashi Ueda, Yasuhiko Iida, Tomoki Yoneyama, Tomoki Kawai, Mikako Ogawa, Yasuhiro Magata, Hideo Saji
SYNAPSE, 65, 1, 77, 83, Jan. 2011, [Peer-reviewed]
English, Scientific journal - Rational chemical design of the next generation of molecular imaging probes based on physics and biology: mixing modalities, colors and signals
Hisataka Kobayashi, Michelle R. Longmire, Mikako Ogawa, Peter L. Choyke
CHEMICAL SOCIETY REVIEWS, 40, 9, 4626, 4648, 2011, [Peer-reviewed]
English - Synthesis and biological evaluation of radio-iodinated benzimidazoles as SPECT imaging agents for NR2B subtype of NMDA receptor
Takeshi Fuchigami, Hiroshi Yamaguchi, Mikako Ogawa, Le Biao, Morio Nakayama, Mamoru Haratake, Yasuhiro Magata
BIOORGANIC & MEDICINAL CHEMISTRY, 18, 21, 7497, 7506, Nov. 2010, [Peer-reviewed]
English, Scientific journal - Multiplexed imaging in cancer diagnosis: applications and future advances
Hisataka Kobayashi, Michelle R. Longmire, Mikako Ogawa, Peter L. Choyke, Satomi Kawamoto
LANCET ONCOLOGY, 11, 6, 589, 595, Jun. 2010, [Peer-reviewed]
English - X-ray computed tomography contrast agents prepared by seeded growth of gold nanoparticles in PEGylated dendrimer
Chie Kojima, Yasuhito Umeda, Mikako Ogawa, Atsushi Harada, Yasuhiro Magata, Kenji Kono
NANOTECHNOLOGY, 21, 24, 245104, Jun. 2010, [Peer-reviewed]
English, Scientific journal - New Strategies for Fluorescent Probe Design in Medical Diagnostic Imaging
Hisataka Kobayashi, Mikako Ogawa, Raphael Alford, Peter L. Choyke, Yasuteru Urano
CHEMICAL REVIEWS, 110, 5, 2620, 2640, May 2010, [Peer-reviewed]
English - New Nanosized Biocompatible MR Contrast Agents Based on Lysine-Dendri-Graft Macromolecules
Mikako Ogawa, Celeste A. S. Regino, Bernardo Marcelino, Mark Williams, Nobuyuki Kosaka, L. Henry Bryant, Peter L. Choyke, Hisataka Kobayashi
BIOCONJUGATE CHEMISTRY, 21, 5, 955, 960, May 2010, [Peer-reviewed]
English, Scientific journal - High sensitivity detection of cancer in vivo using a dual-controlled activation fluorescent imaging probe based on H-dimer formation and pH activation
Mikako Ogawa, Nobuyuki Kosaka, Celeste A. S. Regino, Makoto Mitsunaga, Peter L. Choyke, Hisataka Kobayashi
MOLECULAR BIOSYSTEMS, 6, 5, 888, 893, May 2010, [Peer-reviewed]
English, Scientific journal - Synthesis and evaluation of new imaging agent for central nicotinic acetylcholine receptor alpha(7) subtype
Mikako Ogawa, Shingo Nishiyama, Hideo Tsukada, Kentaro Hatano, Takeshi Fuchigami, Hiroshi Yamaguchi, Yoshitaka Matsushima, Kengo Ito, Yasuhiro Magata
NUCLEAR MEDICINE AND BIOLOGY, 37, 3, 347, 355, Apr. 2010, [Peer-reviewed]
English, Scientific journal - 125I標識ベンズイミダゾール誘導体のNMDA受容体NR2Bサブタイプ機能診断薬剤としての基礎的評価
淵上 剛志, 山口 博司, 小川 美香子, 楽 豹, 中山 守雄, 間賀田 泰寛
日本薬学会年会要旨集, 130年会, 4, 124, 124, (公社)日本薬学会, Mar. 2010, [Peer-reviewed]
Japanese - 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, Mar. 2010, [Peer-reviewed]
English, Scientific journal - Semiquantitative assessment of the microdistribution of fluorescence-labeled monoclonal antibody in small peritoneal disseminations of ovarian cancer
Nobuyuki Kosaka, Mikako Ogawa, David S. Paik, Chang H. Paik, Peter L. Choyke, Hisataka Kobayashi
CANCER SCIENCE, 101, 3, 820, 825, Mar. 2010, [Peer-reviewed]
English, Scientific journal - Two-Step Synthesis of Galactosylated Human Serum Albumin as a Targeted Optical Imaging Agent for Peritoneal Carcinomatosis
Celeste Aida S. Regino, Mikako Ogawa, Raphael Alford, Karen J. Wong, Noboyuki Kosaka, Mark Williams, Brian J. Feild, Masatoshi Takahashi, Peter L. Choyke, Hisataka Kobayashi
JOURNAL OF MEDICINAL CHEMISTRY, 53, 4, 1579, 1586, Feb. 2010, [Peer-reviewed]
English, Scientific journal - Microdistribution of Fluorescently-labeled Monoclonal Antibody in a Peritoneal Dissemination model of Ovarian Cancer
Nobuyuki Kosaka, Mikako Ogawa, David S. Paik, Chang H. Paik, Peter L. Choyke, Hisataka Kobayashi
REPORTERS, MARKERS, DYES, NANOPARTICLES, AND MOLECULAR PROBES FOR BIOMEDICAL APPLICATIONS II, 7576, 2010, [Peer-reviewed]
English, International conference proceedings - Fluorescence lifetime imaging of activatable target specific molecular probes
Raphael Alford, Mikako Ogawa, Moinuddin Hassan, Amir H. Gandjbakhche, Peter L. Choyke, Hisataka Kobayashi
CONTRAST MEDIA & MOLECULAR IMAGING, 5, 1, 1, 8, Jan. 2010, [Peer-reviewed]
English, Scientific journal - In Vivo Real-Time, Multicolor, Quantum Dot Lymphatic Imaging
Nobuyuki Kosaka, Mikako Ogawa, Noriko Sato, Peter L. Choyke, Hisataka Kobayashi
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 129, 12, 2818, 2822, Dec. 2009, [Peer-reviewed]
English, Scientific journal - New approaches to lymphatic imaging.
Lucarelli RT, Ogawa M, Kosaka N, Turkbey B, Kobayashi H, Choyke PL
Lymphatic research and biology, 7, 4, 205, 214, Dec. 2009, [Peer-reviewed] - Clinical implications of near-infrared fluorescence imaging in cancer
Nobuyuki Kosaka, Mikako Ogawa, Peter L. Choyke, Hisataka Kobayashi
FUTURE ONCOLOGY, 5, 9, 1501, 1511, Nov. 2009, [Peer-reviewed]
English - Dual-Modality Molecular Imaging Using Antibodies Labeled with Activatable Fluorescence and a Radionuclide for Specific and Quantitative Targeted Cancer Detection
Mikako Ogawa, Celeste A. S. Regino, Jurgen Seidel, Michael V. Green, Wenze Xi, Mark Williams, Nobuyuki Kosaka, Peter L. Choyke, Hisataka Kobayashi
BIOCONJUGATE CHEMISTRY, 20, 11, 2177, 2184, Nov. 2009, [Peer-reviewed]
English, Scientific journal - Toxicity of Organic Fluorophores Used in Molecular Imaging: Literature Review
Raphael Alford, Haley M. Simpson, Josh Duberman, G. Craig Hill, Mikako Ogawa, Celeste Regino, Hisataka Kobayashi, Peter L. Choyke
MOLECULAR IMAGING, 8, 6, 341, 354, Nov. 2009, [Peer-reviewed]
English - ニコチン慢性投与中における脳循環代謝変化の小動物PETによる追跡
山口 博司, 二ツ橋 昌実, 尾内 康臣, 鳥塚 達郎, 小杉 睦, 小川 美香子, 淵上 剛志, 間賀田 泰寛
核医学, 46, 3, 327, 327, (一社)日本核医学会, Sep. 2009, [Peer-reviewed]
Japanese - Development of N-[C-11]methylamino 4-hydroxy-2(1H)-quinolone derivatives as PET radioligands for the glycine-binding site of NMDA receptors
Takeshi Fuchigami, Terushi Haradahira, Noriko Fujimoto, Yumiko Nojiri, Takahiro Mukai, Fumihiko Yamamoto, Takashi Okauchi, Jun Maeda, Kazutoshi Suzuki, Tetsuya Suhara, Hiroshi Yamaguchi, Mikako Ogawa, Yasuhiro Magata, Minoru Maeda
BIOORGANIC & MEDICINAL CHEMISTRY, 17, 15, 5665, 5675, Aug. 2009, [Peer-reviewed]
English, Scientific journal - Imaging of Tumor Angiogenesis: Functional or Targeted?
Baris Turkbey, Hisataka Kobayashi, Mikako Ogawa, Marcelino Bernardo, Peter L. Choyke
AMERICAN JOURNAL OF ROENTGENOLOGY, 193, 2, 304, 313, Aug. 2009, [Peer-reviewed]
English - H-Type Dimer Formation of Fluorophores: A Mechanism for Activatable, in Vivo Optical Molecular Imaging
Mikako Ogawa, Nobuyuki Kosaka, Peter L. Choyke, Hisataka Kobayashi
ACS CHEMICAL BIOLOGY, 4, 7, 535, 546, Jul. 2009, [Peer-reviewed]
English, Scientific journal - In Vivo Stable Tumor-Specific Painting in Various Colors Using Dehalogenase-Based Protein-Tag Fluorescent Ligands
Nobuyuki Kosaka, Mikako Ogawa, Peter L. Choyke, Natasha Karassina, Cesear Corona, Mark McDougall, David T. Lynch, Clifford C. Hoyt, Richard M. Levenson, Georgyi V. Los, Hisataka Kobayashi
BIOCONJUGATE CHEMISTRY, 20, 7, 1367, 1374, Jul. 2009, [Peer-reviewed]
English, Scientific journal - Multicolor in vivo targeted imaging to guide real-time surgery of HER2-positive micrometastases in a two-tumor coincident model of ovarian cancer
Michelle Longmire, Nobuyuki Kosaka, Mikako Ogawa, Peter L. Choyke, Hisataka Kobayashi
CANCER SCIENCE, 100, 6, 1099, 1104, Jun. 2009, [Peer-reviewed]
English, Scientific journal - Multicolor imaging of lymphatic function with two nanomaterials: quantum dot-labeled cancer cells and dendrimer-based optical agents
Hisataka Kobayashi, Mikako Ogawa, Nobuyuki Kosaka, Petet L. Choyke, Yasuteru Urano
NANOMEDICINE, 4, 4, 411, 419, Jun. 2009, [Peer-reviewed]
English, Scientific journal - Central in Vivo Nicotinic Acetylcholine Receptor Imaging Agents for Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT)
Mikako Ogawa, Hideo Tsukada, Kentaro Hatano, Yasuomi Ouchi, Hideo Saji, Yasuhiro Magata
BIOLOGICAL & PHARMACEUTICAL BULLETIN, 32, 3, 337, 340, Mar. 2009, [Peer-reviewed]
English, Scientific journal - Fluorophore-Quencher Based Activatable Targeted Optical Probes for Detecting in Vivo Cancer Metastases
Mikako Ogawa, Nobuyuki Kosaka, Michelle R. Longmire, Yasuteru Urano, Peter L. Choyke, Hisataka Kobayashi
MOLECULAR PHARMACEUTICS, 6, 2, 386, 395, Mar. 2009, [Peer-reviewed]
English, Scientific journal - In vivo Molecular Imaging of Cancer with a Quenching Near-Infrared Fluorescent Probe Using Conjugates of Monoclonal Antibodies and Indocyanine Green
Mikako Ogawa, Nobuyuki Kosaka, Peter L. Choyke, Hisataka Kobayashi
CANCER RESEARCH, 69, 4, 1268, 1272, Feb. 2009, [Peer-reviewed]
English, Scientific journal - Activatable optical imaging probes with various fluorophore-quencher combinations
Mikako Ogawa, Nobuyuki Kosaka, Yasuteru Urano, Peter L. Choyke, Hisataka Kobayashi
Progress in Biomedical Optics and Imaging - Proceedings of SPIE, 7190, 2009, [Peer-reviewed]
English, International conference proceedings - Activatable optical imaging probes with various fluorophore-quencher combinations
Mikako Ogawa, Nobuyuki Kosaka, Yasuteru Urano, Peter L. Choyke, Hisataka Kobayashi
REPORTERS, MARKERS, DYES, NANOPARTICLES, AND MOLECULAR PROBES FOR BIOMEDICAL APPLICATIONS, 7190, 2009, [Peer-reviewed]
English, International conference proceedings - Tumor-Specific Detection of an Optically Targeted Antibody Combined with a Quencher-Conjugated Neutravidin "Quencher-Chaser": A Dual "Quench and Chase" Strategy to Improve Target to Nontarget Ratios for Molecular Imaging of Cancer
Mikako Ogawa, Nobuyuki Kosaka, Peter L. Choyke, Hisataka Kobayashi
BIOCONJUGATE CHEMISTRY, 20, 1, 147, 154, Jan. 2009, [Peer-reviewed]
English, Scientific journal - In vivo target-specific activatable near-infrared optical labeling of humanized monoclonal antibodies
Mikako Ogawa, Celeste A. S. Regino, Peter L. Choyke, Hisataka Kobayashi
MOLECULAR CANCER THERAPEUTICS, 8, 1, 232, 239, Jan. 2009, [Peer-reviewed]
English, Scientific journal - Multi-targeted multi-color in vivo optical imaging in a model of disseminated peritoneal ovarian cancer
Nobuyuki Kosaka, Mikako Ogawa, Michelle R. Longmire, Peter L. Choyke, Hisataka Kobayashi
JOURNAL OF BIOMEDICAL OPTICS, 14, 1, 014023, Jan. 2009, [Peer-reviewed]
English, Scientific journal - Molecular probes for the in vivo imaging of cancer
Raphael Alford, Mikako Ogawa, Peter L. Choyke, Hisataka Kobayashi
MOLECULAR BIOSYSTEMS, 5, 11, 1279, 1291, 2009, [Peer-reviewed]
English - 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, Oct. 2008, [Peer-reviewed]
English, Scientific journal - 小動物イメージング装置を用いて求めるラット脳循環代謝に及ぼす体温および麻酔管理の影響に関する検討
山口 博司, 二ツ橋 昌実, 尾内 康臣, 鳥塚 達郎, 小杉 睦, 小川 美香子, 淵上 剛志, 間賀田 泰寛
核医学, 45, 3, S199, S199, (一社)日本核医学会, Sep. 2008, [Peer-reviewed]
Japanese - Determination of optimal rhodamine fluorophore for in vivo optical imaging
Michelle R. Longmire, Mikako Ogawa, Yukihiro Hama, Nobuyuki Kosaka, Celeste A. S. Regino, Peter L. Choyke, Hisataka Kobayashi
BIOCONJUGATE CHEMISTRY, 19, 8, 1735, 1742, Aug. 2008, [Peer-reviewed]
English, Scientific journal - Radiosynthesis and in vivo evaluation of N-[C-11]methylated imidazopyridineacetamides as PET tracers for peripheral benzodiazepine receptors
Katsuhiko Sekimata, Kentaro Hatano, Mikako Ogawa, Junichiro Abe, Yasuhiro Magata, Giovanni Biggio, Mariangela Serra, Valentino Laquintana, Nunzio Denora, Andrea Latrofa, Giuseppe Trapani, Gaetano Liso, Kengo Ito
NUCLEAR MEDICINE AND BIOLOGY, 35, 3, 327, 334, Apr. 2008, [Peer-reviewed]
English, Scientific journal - 5-Iodo-A-85380, a specific ligand for alpha A beta 2 nicotinic acetylcholine receptors, prevents glutamate neurotoxicity in rat cortical cultured neurons
Masashi Ueda, Yasuhiko Iida, Youji Kitamura, Hidekazu Kawashima, Mikako Ogawa, Yasuhiro Mayata, Hideo Saji
BRAIN RESEARCH, 1199, 46, 52, Mar. 2008, [Peer-reviewed]
English, Scientific journal - Difference in brain distributions of carbon 11-labeled 4-hydroxy-2(1H)-quinolones as PET radioligands for the glycine-binding site of the NMDA ion channel
Takeshi Fuchigami, Terushi Haradahira, Noriko Fujimoto, Takashi Okauchi, Jun Maeda, Kazutoshi Suzuki, Tetsuya Suhara, Futnihiko Yamamoto, Shigeki Sasaki, Takahiro Mukai, Hiroshi Yamaguchi, Mikako Ogawa, Yasuhiro Magata, Minoru Maeda
NUCLEAR MEDICINE AND BIOLOGY, 35, 2, 203, 212, Feb. 2008, [Peer-reviewed]
English - Increased binding potential of [C-11]Raclopride during unilateral continuous microinjection of nicotine in rat striatum observed by positron emission tomography
Toshihisa Tajima, Kentaro Hatano, Mitsuru Suzuki, Mikako Ogawa, Yojiro Sakiyama, Takashi Kato, Hidetoshi Endo, Hisayuki Miura, Michitaka Matsubara, Kengo Ito
SYNAPSE, 61, 12, 943, 950, Dec. 2007, [Peer-reviewed]
English, Scientific journal - 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, Nov. 2007, [Peer-reviewed]
English, Scientific journal - [18F]FDG-PETを用いた乳酸の脳エネルギー源としての役割に関する検討
小川 美香子, 尾内 康臣, 鳥塚 達郎, 二ツ橋 昌実, 山口 博司, 淵上 剛志, 間賀田 泰寛
核医学, 44, 3, 279, 279, (一社)日本核医学会, Oct. 2007, [Peer-reviewed]
Japanese - Application of F-18-FDG PET for monitoring the therapeutic effect of antiinflammatory drugs on stabilization of vulnerable atherosclerotic plaques
Mikako Ogawa, Yasuhiro Magata, Takashi Kato, Kentaro Hatano, Seigo Ishino, Takahiro Mukai, Masashi Shiomi, Kengo Ito, Hideo Saji
JOURNAL OF NUCLEAR MEDICINE, 47, 11, 1845, 1850, Nov. 2006, [Peer-reviewed]
English, Scientific journal - [2-11C]isopropyl-, [1-11C]ethyl-, and [ 11C]methyl-labeled phenoxyphenyl acetamide derivatives as positron emission tomography ligands for the peripheral benzodiazepine receptor: Radiosynthesis, uptake, and in vivo binding in brain
Ming-Rong Zhang, Masanao Ogawa, Jun Maeda, Takehito Ito, Junko Noguchi, Katsushi Kumata, Takashi Okauchi, Tetsuya Suhara, Kazutoshi Suzuki
Journal of Medicinal Chemistry, 49, 9, 2735, 2742, 04 May 2006, [Peer-reviewed]
English, Scientific journal - A catheter-based intravascular radiation detector of vulnerable plaques
R Hosokawa, N Kambara, M Ohba, T Mukai, M Ogawa, H Motomura, N Kume, H Saji, T Kita, R Nohara
JOURNAL OF NUCLEAR MEDICINE, 47, 5, 863, 867, May 2006, [Peer-reviewed]
English, Scientific journal - Synthesis and evaluation of [I-125]I-TSA as a brain nicotinic acetylcholine receptor alpha(7) subtype imaging agent
M Ogawa, R Tatsumi, M Fujio, KB Jiro, Y Magata
NUCLEAR MEDICINE AND BIOLOGY, 33, 3, 311, 316, Apr. 2006, [Peer-reviewed]
English, Scientific journal - 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, Feb. 2006, [Peer-reviewed]
English, Scientific journal - Understanding of cerebral energy metabolism by dynamic living brain slice imaging system with [ (18)F]FDG
M Ogawa, H Watabe, N Teramoto, Y Miyake, T Hayashi, H Iida, T Murata, Y Magata
NEUROSCIENCE RESEARCH, 52, 4, 357, 361, Aug. 2005, [Peer-reviewed]
English, Scientific journal - A catheter-based radiation detector for endovascular detection of atheromatous plaques
T Mukai, R Nohara, M Ogawa, S Ishino, N Kambara, K Kataoka, T Kanoi, K Saito, H Motomura, J Konishi, H Saji
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, 31, 9, 1299, 1303, Sep. 2004, [Peer-reviewed]
English, Scientific journal - (18)F-FDG accumulation in atherosclerotic plaques: Immunohistochemical and PET imaging study
M Ogawa, S Ishino, T Mukai, D Asano, N Teramoto, H Watabe, N Kudomi, M Shiomi, Y Magata, H Iida, H Saji
JOURNAL OF NUCLEAR MEDICINE, 45, 7, 1245, 1250, Jul. 2004, [Peer-reviewed]
English, Scientific journal - 5-[I-123]iodo-A-85380: assessment of pharmacological safety, radiation dosimetry and SPECT imaging of brain nicotinic receptors in healthy human subjects
M Ueda, Y Iida, T Mukai, M Mamede, K Ishizu, M Ogawa, Y Magata, J Konishi, H Saji
ANNALS OF NUCLEAR MEDICINE, 18, 4, 337, 344, Jun. 2004, [Peer-reviewed]
English, Scientific journal - Evaluation of 5-(11)C-methyl-A-85380 as an imaging agent for PET invesvigations of brain nicotinic acetylcholine receptors
Y Iida, M Ogawa, M Ueda, A Tominaga, H Kawashima, Y Magata, S Nishiyama, H Tsukada, T Mukai, H Saji
JOURNAL OF NUCLEAR MEDICINE, 45, 5, 878, 884, May 2004, [Peer-reviewed]
English, Scientific journal - Development of a new radioligand, N-(5-fluoro-2-phenoxyphenyl)-N-(2-[F-18]fluoroethyl-5-methoxybenzyl)acetamide, for PET imaging of peripheral benzodiazepine receptor in primate brain
MR Zhang, J Maeda, M Ogawa, J Noguchi, T Ito, Y Yoshida, T Okauchi, S Obayashi, T Suhara, K Suzuki
JOURNAL OF MEDICINAL CHEMISTRY, 47, 9, 2228, 2235, Apr. 2004, [Peer-reviewed]
English, Scientific journal - 新規PET用脳内ニコチン受容体イメージング剤5-[11C]C2H5-A-85380([11C]5EA)の開発
小川 美香子, 西山 新吾, 塚田 秀夫, 飯田 靖彦, 佐治 英郎, 間賀田 泰寛
日本薬学会年会要旨集, 124年会, 3, 65, 65, (公社)日本薬学会, Mar. 2004
Japanese - Endogenous dopamine release induced by repetitive transcranial magnetic stimulation over the primary motor cortex: An [11]raclopride positron emission tomography study in anesthetized macaque monkeys
T Ohnishi, T Hayashi, S Okabe, Nonaka, I, H Matsuda, H Iida, E Imabayashi, H Watabe, Y Miyake, M Ogawa, N Teramoto, Y Ohta, N Ejima, T Sawada, Y Ugawa
BIOLOGICAL PSYCHIATRY, 55, 5, 484, 489, Mar. 2004, [Peer-reviewed]
English, Scientific journal - Imaging of vulnerable atherosclerotic plaque with [ (18)F]FDG-PET: an animal atherosclerosis model study
M Ogawa, T Mukai, S Ishino, N Teramoto, H Watabe, N Kudomi, M Shiomi, Y Magata, H Iida, H Saji
QUANTITATION IN BIOMEDICAL IMAGING WITH PET AND MRI, 1265, 266, 268, 2004, [Peer-reviewed]
English, International conference proceedings - Development of injectable O-15 oxygen and its application for estimation of OEF
T Temma, Y Magata, H Iida, T Hayashi, M Ogawa, T Mukai, Y Iida, H Tsukada, J Konishi, H Saji
QUANTITATION IN BIOMEDICAL IMAGING WITH PET AND MRI, 1265, 262, 265, 2004, [Peer-reviewed]
English, International conference proceedings - Effects of monoamine oxidase inhibitors on the diethyldithiocarbamate-induced enhancement of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity in C57BL/6 mice
K Takahata, S Shimazu, F Yoneda, M Ogawa, Y Iida, H Saji
JOURNAL OF NEURAL TRANSMISSION, 110, 8, 859, 869, Aug. 2003, [Peer-reviewed]
English, Scientific journal - Development of injectable O-15 oxygen and estimation of rat OEF
Y Magata, T Temma, T Iida, M Ogawa, T Mukai, T Iida, T Morimoto, J Konishi, H Saji
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 23, 6, 671, 676, Jun. 2003, [Peer-reviewed]
English, Scientific journal - Development of a GSO detector assembly for a continuous blood sampling system
N Kudomi, E Choi, S Yamamoto, H Watabe, KM Kim, M Shidahara, M Ogawa, N Teramoto, E Sakamoto, H Iida
IEEE TRANSACTIONS ON NUCLEAR SCIENCE, 50, 1, 70, 73, Feb. 2003, [Peer-reviewed]
English, Scientific journal - Absolute quantitation of regional myocardial blood flow of rats using dynamic pinhole SPECT
T Aoi, H Watabe, HM Deloar, M Ogawa, N Teramoto, N Kudomi, T Oota, KM Kim, T Matsuda, H Iida
2002 IEEE NUCLEAR SCIENCE SYMPOSIUM, CONFERENCE RECORD, VOLS 1-3, 1780, 1783, 2003, [Peer-reviewed]
English, International conference proceedings - Performance test and application of GSO detector assembly for a continuous blood sampling system
N Kudomi, E Choi, S Yamamoto, H Watabe, KM Kim, T Hayashi, M Ogawa, N Teramoto, E Sakamoto, H Iida
2002 IEEE NUCLEAR SCIENCE SYMPOSIUM, CONFERENCE RECORD, VOLS 1-3, 1648, 1651, 2003, [Peer-reviewed]
English, International conference proceedings - Direct electrophilic radiofluorination of a cyclic RGD peptide for in vivo alpha(v)beta(3) integrin related tumor imaging
M Ogawa, K Hatano, S Oishi, Y Kawasumi, N Fujii, M Kawaguchi, R Doi, M Imamura, M Yamamoto, K Ajito, T Mukai, H Saji, K Ito
NUCLEAR MEDICINE AND BIOLOGY, 30, 1, 1, 9, Jan. 2003, [Peer-reviewed]
English, Scientific journal - Synthesis and evaluation of 1-[ (3R,4R)-1-cyclooctylmethyl-3-hydroxymethyl-4-piperidyl]-3-[C-11]ethyl-1,3-dihydro-2H-benzimidazol-2-one as a brain ORL1 receptor imaging agent for positron emission tomography
M Ogawa, K Hatano, Y Kawasumi, K Ishiwata, K Kawamura, S Ozaki, K Ito
NUCLEAR MEDICINE AND BIOLOGY, 30, 1, 51, 59, Jan. 2003, [Peer-reviewed]
English, Scientific journal - In vivo imaging of brain dopaminergic neurotransmission system in small animals with high-resolution single photon emission computed tomography
H Saji, Y Iida, H Kawashima, M Ogawa, Y Kitamura, T Mukai, S Shimazu, F Yoneda
ANALYTICAL SCIENCES, 19, 1, 67, 71, Jan. 2003, [Peer-reviewed]
English, Scientific journal - Norepinephrine transporter density as a causative factor in alterations in MIBG myocardial uptake in NIDDM model rats
Y Kiyono, Y Iida, H Kawashima, M Ogawa, N Tamaki, H Nishimura, H Saji
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, 29, 8, 999, 1005, Aug. 2002, [Peer-reviewed]
English, Scientific journal - Age-related changes of myocardial norepinephrine transporter density in rats: implications for differential cardiac accumulation of MIBG in aging
Y Kiyono, N Kanegawa, H Kawashima, Y Iida, T Kinoshita, N Tamaki, H Nishimura, M Ogawa, H Saji
NUCLEAR MEDICINE AND BIOLOGY, 29, 6, 679, 684, Aug. 2002, [Peer-reviewed]
English, Scientific journal - Evaluation of radioiodinated 5-iodo-3-(2(S)-azetidinylmethoxy)pyridine as a ligand for SPECT investigations of brain nicotinic acetylcholine receptors
H Saji, M Ogawa, M Ueda, Y Iida, Y Magata, A Tominaga, H Kawashima, Y Kitamura, M Nakagawa, Y Kiyono, T Mukai
ANNALS OF NUCLEAR MEDICINE, 16, 3, 189, 200, May 2002, [Peer-reviewed]
English, Scientific journal - Norepinephrine transporter density as a causative factor in alterations in MIBG myocardial uptake in NIDDM model rats
Yasushi Kiyono, Yasuhiko Iida, Hidekazu Kawashima, Mikako Ogawa, Nagara Tamaki, Hiroshi Nishimura, Hideo Saji
European Journal of Nuclear Medicine, 29, 8, 999, 1005, 2002, [Peer-reviewed]
English, Scientific journal - Direct single step F-18 fluorination of peptides.
Ogawa M, Hatano K, Oishi S, Miyake Y, Kawasumi Y, Ito K, Fujii N, Iida H
Journal of Nuclear Medicine, 43, 5, 137P, 2002, [Peer-reviewed] - Synthesis and in vivo evaluation of [C-11]methyl-Ro 64-6198 as an ORL1 receptor imaging agent
M Ogawa, K Hatano, Y Kawasumi, E Wichmann, K Ito
NUCLEAR MEDICINE AND BIOLOGY, 28, 8, 941, 947, Nov. 2001, [Peer-reviewed]
English, Scientific journal - PET用ニコチン性アセチルコリンレセプター機能診断薬剤の開発
冨永 亜希子, 飯田 靖彦, 間賀田 泰寛, 佐治 英郎, 小川 美香子
核医学, 37, 5, 571, 571, (一社)日本核医学会, Sep. 2000
Japanese - ニコチン性アセチルコリンレセプター機能診断薬剤の開発
小川 美香子, 飯田 靖彦, 間賀田 泰寛, 佐治 英郎
核医学, 36, 6, 651, 651, (一社)日本核医学会, Aug. 1999
Japanese - SPECT用ニコチン性アセチルコリンレセプター機能診断薬剤の開発
飯田 靖彦, 小川 美香子, 中川 雅喜, 間賀田 泰寛, 佐治 英郎
日本薬学会年会要旨集, 119年会, 4, 123, 123, (公社)日本薬学会, Mar. 1999
Japanese - Compartment analysis of cerebral glucose metabolism and in vitro glucose-metabolizing enzyme activities in the rat brain
Y Ouchi, H Fukuyama, S Matsuzaki, M Ogawa, J Kimura, H Tsukada, T Kakiuchi, T Kosugi, S Nishiyama
BRAIN RESEARCH, 706, 2, 267, 272, Jan. 1996, [Peer-reviewed]
English, Scientific journal - Cholinergic projection from the basal forebrain and cerebral glucose metabolism in rats: A dynamic PET study
Y Ouchi, H Fukuyama, M Ogawa, H Yamauchi, J Kimura, Y Magata, Y Yonekura, J Konishi
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 16, 1, 34, 41, Jan. 1996, [Peer-reviewed]
English, Scientific journal - SCOPOLAMINE ABOLISHES CEREBRAL BLOOD-FLOW RESPONSE TO SOMATOSENSORY STIMULATION IN ANESTHETIZED CATS - PET STUDY
M OGAWA, Y MAGATA, Y OUCHI, H FUKUYAMA, H YAMAUCHI, J KIMURA, Y YONEKURA, J KONISHI
BRAIN RESEARCH, 650, 2, 249, 252, Jul. 1994, [Peer-reviewed]
English, Scientific journal - CROSSED CEREBELLAR HYPOPERFUSION IN UNILATERAL MAJOR CEREBRAL-ARTERY OCCLUSIVE DISORDERS
H YAMAUCHI, H FUKUYAMA, S YAMAGUCHI, T DOI, M OGAWA, Y OUCHI, J KIMURA, N SADATOH, Y YONEKURA, N TAMAKI, J KONISHI
JOURNAL OF NUCLEAR MEDICINE, 33, 9, 1637, 1641, Sep. 1992, [Peer-reviewed]
English, Scientific journal
Other Activities and Achievements
- 放射線によるDNA損傷は遅延性のミトコンドリア由来の細胞内活性酸素種を上昇させるか?
稲波修, 加藤千博, 安井博宣, 後藤悠人, 小川美香子, 日本酸化ストレス学会学術集会プログラム・抄録集, 76th, 2023 - Analysis of X-ray responsiveness of phthalocyanine derivatives for development of caged compounds that can be used deep in vivo
山下柾, 松廣志乃, 高倉栄男, 中島孝平, 稲波修, 小川美香子, 日本薬学会年会要旨集(Web), 143rd, 2023 - Investigation of a reaction mechanism of photoimmunotherapy using ESR
後藤悠人, 高倉栄男, 中島孝平, 稲波修, 小川美香子, 日本薬学会年会要旨集(Web), 143rd, 2023 - Analysis of radiation reaction mechanisms of hypervalent iodine compounds using ESR for the development of radiation-responsive caged compounds.
稲波修, 榎本将聖, 我喜屋祥, 中島孝平, 小川美香子, 電子スピンサイエンス学会年会講演要旨集, 62nd (CD-ROM), 2023 - Analysis of azo cleavage reaction for development of X-ray induced caged compounds
小河原浩輝, 高倉栄男, 中島孝平, 稲波修, 小川美香子, 日本薬学会年会要旨集(Web), 143rd, 2023 - Analysis of X-ray response of hypervalent iodine compounds for development of X-ray caged compounds
榎本将聖, 高倉栄男, 中島考平, 稲波修, 小川美香子, 日本薬学会年会要旨集(Web), 143rd, 2023 - Development of 191Pt-labeled compounds inducing DNA damage efficiently
尾幡穂乃香, 尾幡穂乃香, 辻厚至, 永津弘太郎, 小川美香子, ZHANG Ming Rong, 日本薬学会年会要旨集(Web), 143rd, 2023 - Development of X-ray activated caged compounds by using azo bond cleavage
小河原浩輝, 高倉栄男, 中島孝平, 斉田謙一郎, KUMAR Sonu, 小林正人, 武次徹也, 稲浪修, 小川美香子, 日本癌学会学術総会抄録集(Web), 82nd, 2023 - がんを高感度に検出可能なpH応答性光音響イメージング剤の開発
土屋 光輝, 高倉 栄男, 中島 孝平, 平沢 壮, 能塚 雄介, 石原 美弥, 山岡 禎久, 小川 美香子, JSMI Report, 15, 2, 76, 76, Apr. 2022
日本分子イメージング学会, Japanese - がんを高感度に検出可能なpH応答性光音響イメージング剤の開発
土屋 光輝, 高倉 栄男, 中島 孝平, 平沢 壮, 能塚 雄介, 石原 美弥, 山岡 禎久, 小川 美香子, JSMI Report, 15, 2, 125, 125, Apr. 2022
日本分子イメージング学会, Japanese - Analysis of X-ray-triggered reaction of phthalocyanine derivatives for development of caged compound activated in deep tissue
後藤悠人, 松廣志乃, 山下柾, 高倉栄男, 中島孝平, 稲波修, 小川美香子, 電子スピンサイエンス学会年会講演要旨集, 61st (CD-ROM), 2022 - Comparison and investigation of the cell-killing effects of photoimmunotherapy (PIT) and photodynamic therapy (PDT) in hypoxic cancer cells
白川晴香, 後藤悠人, 中島孝平, 高倉栄男, 安井博宣, 小川美香子, 稲波修, 電子スピンサイエンス学会年会講演要旨集, 61st (CD-ROM), 2022 - Analysis of X-ray response of hypervalent iodine compounds for development of X-ray caged compounds
榎本将聖, 高倉栄男, 中島孝平, 稲波修, 小川美香子, バイオメディカル分析科学シンポジウム講演要旨集, 34th, 2022 - Analysis of X-ray responsiveness of phthalocyanine derivatives for development of caged compounds
山下柾, 松廣志乃, 高倉栄男, 中島孝平, 稲波修, 小川美香子, バイオメディカル分析科学シンポジウム講演要旨集, 34th, 2022 - Development of X-ray induced caged compounds using azo bond cleavage
小河原浩輝, 高倉栄男, 中島孝平, 稲波修, 小川美香子, バイオメディカル分析科学シンポジウム講演要旨集, 34th, 2022 - Analysis of therapeutic effects and photochemical reaction of a new red-shifted photosensitizer for photoimmunotherapy
後藤悠人, 安藤完太, 中島孝平, 高倉栄男, 稲波修, 小川美香子, バイオメディカル分析科学シンポジウム講演要旨集, 34th, 2022 - 加速器を用いた白金核種(191Pt)の製造および標識白金錯体の合成
尾幡 穂乃香, 永津 弘太郎, 辻 厚至, 小川 美香子, 張 明栄, アイソトープ・放射線研究発表会, 1, 119, 2021
白金核種191Ptは3日程度の適度な半減期でγ線とAuger電子を放出することから, 抗腫瘍白金製剤のトレーサー研究に利用できるだけでなく, Auger電子治療への応用も期待される。しかし, これまで191Ptは製造法が確立されず, 標識薬剤開発もほとんど行われていない。本研究では加速器を用いたキャリアフリーの191Pt製造法を開発すると共に, シスプラチンと白金キレート化合物の標識合成を実施した。, 公益社団法人 日本アイソトープ協会, Japanese - 光免疫療法によって生じる腫瘍特異的変化に関するPETおよびMRIを用いた解析
中島孝平, 安井博宣, 東川桂, 高倉栄男, 間賀田泰寛, 久下裕司, 小川美香子, 日本癌学会学術総会抄録集(Web), 80th, 2021 - 光免疫療法が腫瘍に及ぼす機能的変化に関するFDG-/FMISO-PETおよびMRI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, 鈴木千恵, 間賀田泰寛, 久下裕司, 小川美香子, 核医学(Web), 58, Supplement, 2021 - 光免疫治療に資するX線誘導による生体深部腫瘍での選択的分子解離の探索(Explore of X-ray induced selective molecular degradation for photoimmuno-therapy targeting deep tissues)
横谷 明徳, 藤井 健太郎, 渡辺 立子, 平戸 未彩紀, 中川 桂一, 稲波 修, 武次 徹也, 小川 美香子, 日本放射線影響学会大会講演要旨集, 63回, 122, 122, Oct. 2020
(一社)日本放射線影響学会, English - Carboxyl-, sulfonyl-, and phosphate-terminal dendrimers as a nanoplatform with lymph node targeting.
Yutaka Nishimoto, Shu Nagashima, Kohei Nakajima, Takayuki Ohira, Tatsumi Sato, Takeshi Izawa, Jyoji Yamate, Kei Higashikawa, Yuji Kuge, Mikako Ogawa, Chie Kojima, International journal of pharmaceutics, 576, 119021, 119021, 07 Jan. 2020, [International Magazine]
The development of drug delivery vehicles to cancer and/or immune cells in lymph nodes is important for cancer diagnosis, therapy, and immunotherapy. We previously reported that anionic carboxyl-terminal dendrimers were accumulated in lymph nodes. In this study, three anionic dendrimers with carboxyl-, sulfonyl-, and phosphate-terminal groups were prepared to examine the lymph node targeting and the association with immune cells in the lymph nodes. These anionic dendrimers were accumulated in the lymph node by intradermal injection. Although the carboxyl- and sulfonyl-terminal dendrimers were diffused from the injection site, the phosphate-terminal dendrimers were mostly retained. The phosphate-terminal dendrimer was recognized by the macrophages, dendritic cells, and B cells in the lymph node, whereas the carboxyl- and sulfonyl-terminal dendrimers were not. Our results show that these anionic dendrimers were accumulated in the lymph node where the association with immune cells could be controlled by the terminal structure of the dendrimer. The phosphate-terminal dendrimer can be used as a nanoplatform for the delivery of some bioactive molecules to some immune cells, including B cells, in the lymph node., English - 免疫賦活マウス腫瘍における抗PD-1治療後の[18F]FDG取り込みに関する検討
富田真由, 鈴木基史, 河野裕允, 中島孝平, 松田拓真, 久下裕二, 小川美香子, 核医学(Web), 57, Supplement, 2020 - PETイメージング剤を用いた動脈硬化病変におけるニコチン受容体の機能解明
鈴木基史, 片山竜樹, 鈴木千恵, 中島孝平, 間賀田泰寛, 小川美香子, 核医学(Web), 57, Supplement, 2020 - Investigation of changes in tumor environment after photoimmunotherapy with［18F］FDG and ［18F］FMISO
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, JSMI Report, 13, 1, 17, 22, Jan. 2020, [Peer-reviewed], [Invited]
Japanese, Introduction international proceedings - 種々のアニオン性末端基をもつデンドリマーを利用したリンパ節へのデリバリー
児島千恵, 長島舟, 西本豊, 大平貴之, 中島孝平, 富田真由, 東川桂, 久下裕司, 小川美香子, 日本DDS学会学術集会プログラム予稿集, 35th, 2019 - Photoinduced anion radical formation of a novel silicon phthalocyanine derivative, IR700. for near-infrared photoimmunotherapy (PIT)
房知輝, 平岡和佳子, 後藤悠人, 高倉栄男, 小川美香子, 稲波修, 電子スピンサイエンス学会年会講演要旨集, 58th, 2019 - 光免疫療法による[18F]FDGおよび[18F]FMISOの集積変化に関する検討
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, 小川美香子, 核医学(Web), 55, Supplement, 2018 - PD-1治療が[18F」FDGのがん組織への集積に与える影響についてのマウスを用いた検討
富田真由, 安井博宣, 東川桂, 中島孝平, 高倉栄男, 志賀哲, 久下裕司, 小川美香子, 核医学(Web), 55, Supplement, 2018 - Tiny cell membrane damage is important for near infrared photoimmunotherapy
Nakajima K, Takakura H, Shimizu Y, Ogawa M, 2017 World Molecular Imaging Congress, Sep. 2017 - Accumulation mechanism of novel PET imaging probe “[18F]DiFA” in hypoxic cells revealed by imaging mass spectrometry
Shimizu Y, Zhao S, Kishi R, Yasui H, Nishijima K, Matsumoto H, Tamaki N, Ogawa M, Kuge Y, The 64nd Society of Nuclear Medicine and Molecular Imaging 2017, Jun. 2017
English, Summary national conference - 光線免疫療法によるがん細胞選択的な膜障害に関する検討
中島孝平, 高倉栄男, 志水陽一, 小川美香子, 第12回日本ケミカルバイオロジー学会, Jun. 2017
Summary national conference - 近赤外光を用いた光線免疫療法における細胞死誘発機序の検証
中島孝平, 志水陽一, 高倉栄男, 小川美香子, 第12回日本分子イメージング学会総会・学術総会, May 2017
Summary national conference - 光線免疫療法のメカニズム解明へ向けた細胞膜傷害に関する検討
中島孝平, 志水陽一, 高倉栄男, 小川美香子, 日本薬学会第137年会, 137年会, 2, 254, 254, Mar. 2017
(公社)日本薬学会, Japanese, Summary national conference - 低酸素イメージング剤“FMISO”の腫瘍集積におけるグルタチオン関連因子の影響
志水陽一, 正木悠紀子, 吉岡健, 東野賢一, 沼田義人, 西嶋剣一, 趙 松吉, 玉木長良, 小川美香子, 久下裕司, 第56回日本核医学会学術総会, Nov. 2016
Summary national conference - マクロファージの極性化18F-FMISOの細胞内集積に与える影響
本村 新, 志水陽一, 高倉栄男, 玉木長良, 久下裕司, 小川美香子, 第56回日本核医学会学術総会, 53, Supplement, Nov. 2016
Summary national conference - 新規低酸素イメージング剤“18F-DiFA”の腫瘍集積能・腫瘍内代謝物評価
志水陽一, 趙松吉, 岸伶美, 安井博宣, 西嶋剣一, 松本博樹, 玉木長良, 小川美香子, 久下裕司, 第16回放射性医薬品画像診断薬研究会, Oct. 2016
Summary national conference - Does FMISO-PET really visualize only hypoxic states?; accumulation mechanism assessment of FMISO in hypoxic cells in combination with mass spectrometry
Shimizu Y, Masaki Y, Yoshioka T, Higashino K, Numata Y, Nishijima K, Zhao S, Tamaki N, Ogawa M, Kuge Y, The 63nd Society of Nuclear Medicine and Molecular Imaging 2016, Jun. 2016
English, Summary national conference - Does FMISO-PET really reflect only hypoxia?; accumulation mechanism assessment with imaging mass spectrometry
Yoichi Shimizu, Yukiko Masaki, Takeshi Yoshioka, Kenichi Higashino, Yoshito Numata, Ken-ichi Nishijima, Songji Zhao, Nagara Tamaki, Mikako Ogawa, Yuji Kuge, JOURNAL OF NUCLEAR MEDICINE, 57, May 2016
English, Summary international conference - イメージング質量分析（IMS）による低酸素診断剤“Pimonidazole”の腫瘍内集積機序の解明
志水陽一, 正木悠紀子, 吉岡健, 東野賢一, 沼田義人, 趙 松吉, 小川美香子, 久下裕司, 第11回日本分子イメージング学会総会・学術総会, May 2016
Summary national conference - 動脈硬化症におけるThrombospondin-4の発現変動解析 核医学診断のための標的バイオマーカーとしての評価
志水 陽一, 半澤 宏子, 趙 芫, 福良 沙霧, 西嶋 剣一, 趙 松吉, 坂本 健, 玉木 長良, 小川 美香子, 久下 裕司, 日本薬学会年会要旨集, 136年会, 3, 119, 119, Mar. 2016
(公社)日本薬学会, Japanese, Summary national conference - Radiolabeled immunoglobulin G visualizes active inflammation in atherosclerosis
Fukura S, Shimizu Y, Hanzawa H, Zhao Y, Zhao S, Nishijima K, Sakamoto T, Tamaki N, Ogawa M, Kuge Y, Ninth Japan-China Joint Seminar on Radiopharmaceutical Chemistry, Nov. 2015
English, Summary national conference - イメージング質量分析法(IMS)による低酸素イメージング剤“FMISO”の腫瘍内代謝・集積機序の経時的評価
志水陽一, 正木悠紀子, 吉岡 健, 田中由香里, 西嶋剣一, 趙 松吉, 東野賢一, 沼田義人, 山口嘉隆, 玉木長良, 小川美香子, 久下裕司, 第55回日本核医学会学術総会, Nov. 2015
Summary national conference - イメージング質量分析法(IMS)による2-nitroimidazoleを母体骨格に有する薬剤の腫瘍低酸素領域への集積機序の解明
志水陽一, 正木悠紀子, 吉岡 健, 田中由香里, 西嶋剣一, 趙 松吉, 東野賢一, 沼田義人, 山口嘉隆, 玉木長良, 小川美香子, 久下裕司, 第15回放射性医薬品・画像診断薬研究会, Sep. 2015
Summary national conference - 動脈硬化病変進行における脂肪酸結合蛋白質（FABP5）の発現変動解析：動脈硬化診断用バイオマーカーとしての評価
志水陽一, 半澤宏子, 趙 芫, 趙 松吉, 坂本 健, 玉木長良, 小川美香子, 久下裕司, 第47回日本動脈硬化学会総会・学術集会, Jul. 2015
Summary national conference - Development of a multimodal imaging probe for vulnerable plaque detection.
Mikako Ogawa, Huijun Zhu, Marten Maess, Mutsumi Kosugi, Takahiro Natsume, Yasuhiro Magata, JOURNAL OF NUCLEAR MEDICINE, 56, 3, May 2015
English, Summary international conference - Cerenkov luminescence imaging with PET probes for brain function analysis
Mikako Ogawa, Mutsumi Kosugi, Yasuhiro Magata, JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS, 58, S152, S152, May 2015
English, Summary international conference - 動脈硬化病変における放射性標識化免疫グロブリンG集積機序の探索
志水陽一, 半澤宏子, 趙 芫, 趙 松吉, 福良沙霧, 西嶋剣一, 坂本 健, 玉木長良, 小川美香子, 久下裕司, 第10回日本分子イメージング学会総会・学術総会, May 2015
Summary national conference - A-15 成体脳神経新生のin vivo 動態解析技術の創出
植木 孝俊, 尾内 康臣, 間賀田 泰寛, 小川 美香子, 岡戸 晴生, 霊長類研究所年報, 44, 83, 83, 04 Dec. 2014
京都大学霊長類研究所, Japanese - Evaluation of brain functions by cerenkov luminescence imaging
M. Ogawa, T. Sunami, M. Sakaida, Y. Matsumoto, Y. Magata, EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, 41, S412, S412, Oct. 2014
English, Summary international conference - Evaluation and comparison of [F-18]FDG and [C-11]choline as atherosclerosis imaging agents
Mikako Ogawa, Yoshiko Kondo, Mutsumi Kosugi, Yasuhiro Magata, JOURNAL OF NUCLEAR MEDICINE, 55, May 2014
English, Summary international conference - Investigation of the development of cerebral infarction using multi-modal imaging
Kazuya Hokamura, Yasuhiro Magata, Mikako Ogawa, Takahiro Natsume, Kazuo Umemura, JOURNAL OF PHARMACOLOGICAL SCIENCES, 124, 149P, 149P, 2014
English, Summary international conference - Photochemical induced thrombosis (PIT)モデルによるイメージング (特集 血栓の画像化・イメージング) -- (血栓とイメージング)
外村 和也, 梅村 和夫, 小川 美香子, Thrombosis medicine, 3, 2, 101, 106, Jun. 2013
先端医学社, Japanese - In vivo atherosclerotic plaque imaging by radiolabeled liposomes
Mikako Ogawa, O. Izumi Umeda, Mutsumi Kosugi, Ayumi Kawai, Yasuhiro Magata, JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS, 56, S247, S247, May 2013
English, Summary international conference - LIVE-CELL IMAGING STUDY ON ANTI-ADIPOGENIC AND APOPTOTIC EFFECTS OF A POLYPHENOLIC RESVERATROL DURING ADIPOCYTE DIFFERENTIATION
H. Ihara, M. Ogawa, Y. Magata, ANNALS OF NUTRITION AND METABOLISM, 63, 1716, 1716, 2013
English, Summary international conference - Intraoperative Evaluation of Blood Perfusion of the Gastric Tube After Esophagectomy With Near-Infrared Fluorescence Imaging
Masaki Sano, Kinji Kamiya, Shinichirou Miyazaki, Naoki Unno, Manabu Ohta, Yoshihiro Hiramatsu, Hirotoshi Kikuchi, Takeshi Fujita, Ichirouta Iino, Yoshiaki Takahashi, Mikako Ogawa, Hiroyuki Konno, GASTROENTEROLOGY, 142, 5, S624, S625, May 2012
English, Summary international conference - Photo-immunotherapy: A super-controlled molecular target-specific cancer theranostics, evolving from the molecular imaging technology
Hisataka Kobayashi, Makoto Mitsunaga, Mikako Ogawa, Peter L. Choyke, ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 243, Mar. 2012
English, Summary international conference - アルツハイマー病における脳内ニコチン性α4β2受容体の変化
尾中康臣, 寺田達弘, 大星有美, 小川美香子, 二ツ橋昌実, 吉川悦次, 岡田裕之, 鳥塚達郎, 菅野敏彦, 谷崎靖夫, 間賀田泰寛, 核医学, 49, 3, 2012 - コラーゲンゲルを基盤とするDDS材料の癌転移抑制効果の発光イメージングによる検証
児島千恵, 渡邊健司, 小川美香子, 末廣智幸, 福原彩乃, 乾隆, 間賀田泰寛, JSMI Report, 5, 2, 2012 - センチネルリンパ節イメージングを目的とした放射性標識γ‐ポリグルタミン酸複合体の開発
佐野紘平, 岩宮由梨子, 黒崎友亮, 小川美香子, 間賀田泰寛, 佐々木均, 大嶋孝志, 前田稔, 向高弘, JSMI Rep, 4, 2, 94, 94, 26 May 2011
日本分子イメージング学会, Japanese - Target-specific photo-activatable immunotherapy (PIT) for cancer based on a monoclonal antibody-photosensitizer conjugate
Makoto Mitsunaga, Mikako Ogawa, Nobuyuki Kosaka, Peter L. Choyke, Hisataka Kobayashi, CANCER RESEARCH, 71, Apr. 2011
English, Summary international conference - 新規プロテアーゼ活性検出蛍光プローブの開発と高感度がんin vivoイメージング
坂部 雅世, 小坂 信行, 光永 眞人, 小川 美香子, Choyke Peter, 浅沼 大祐, 神谷 真子, 長野 哲雄, 小林 久隆, 浦野 泰照, 日本薬学会年会要旨集, 131年会, 4, 123, 123, Mar. 2011
(公社)日本薬学会, Japanese - ヒト脳におけるニコチン受容体リガンド[18F]2FAの結合能の簡便評価法
尾内康臣, 小川美香子, 二ツ橋昌実, 齋藤有里子, 吉川悦次, 岡田裕之, 菅野俊彦, 高井やよ, 八木俊輔, 大星有美, 間賀田泰寛, JSMI Report, 4, 2, 2011 - 転移性腫瘍細胞を標的としたDDS材料のin vitroおよびin vivoにおける薬理活性
児島千恵, 渡邊健司, 末廣智幸, 西阪瑛子, 福原彩乃, 乾隆, 小川美香子, 間賀田泰寛, 日本バイオマテリアル学会大会予稿集, 33rd, 2011 - Quantification of central nicotinic acetylcholine receptor alpha 7 subtype with [C-11](R)MeQAA in the monkey brain
Mikako Ogawa, Hideo Tsukada, Shingo Nishiyama, Oba Hiroyuki, Takeharu Kakiuchi, Norihiro Harada, Yasuhiro Magata, JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS, 54, S253, S253, 2011
English, Summary international conference - What Can Be Seen by [F-18]FDG-PET? Changes in [F-18]FDG Uptake by Foam Cell Formation
Mikako Ogawa, Satoki Nakamura, Mutsumi Kosugi, Yasuhiro Magata, ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 30, 11, E282, E282, Nov. 2010
English, Summary international conference - Semi-quantitative Method for Estimation of Rat CMRglucse Using F-18-FDG and Small Animal in vivo Imaging System
Y. Magata, M. Ogawa, H. Yamaguchi, Y. Ouchi, EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, 37, S388, S388, Oct. 2010
English, Summary international conference - NMDA受容体NR2Bサブタイプの機能イメージングを目的とした放射性ヨウ素標識ベンズイミダゾール誘導体の開発
淵上剛志, 山口博司, 小杉睦, 楽ひょう, 小川美香子, 間賀田泰寛, 核医学, 46, 3, 275, 276, Sep. 2009
(一社)日本核医学会, Japanese - Target-specific activatable molecular imaging probes using conjugates of clinically approved monoclonal antibodies and indocyanine green, a near infrared dye
Mikako Ogawa, Nobuyuki Kosaka, Peter Choyke, Hisataka Kobayashi, CANCER RESEARCH, 69, May 2009
English, Summary international conference - Simultaneous imaging of quantum dot-labeled cancer cell migration and lymphatic drainage using dendrimer-based optical agents
Hisataka Kobayashi, Mikako Ogawa, Nobuyuki Kosaka, Peter Choyke, Yasuteru Urano, CANCER RESEARCH, 69, May 2009
English, Summary international conference - Multi-color in vivo targeted imaging to guide real-time surgery of HER2-positive micro-metastases in a two-tumor coincident model of ovarian cancer
Michelle Longmire, Nobuyuki Kosaka, Mikako Ogawa, Peter Choyke, Hisataka Kobayashi, CANCER RESEARCH, 69, May 2009
English, Summary international conference - NMDA受容体NR2Bサブユニットの機能診断を目的とした放射性ヨウ素標識ベンズイミダゾール誘導体の開発
淵上剛志, 山口博司, 楽ひょう, 小川美香子, 間賀田泰寛, 日本薬学会年会要旨集, 129th, 4, 146, 05 Mar. 2009
Japanese - INOR 440-Fluorescence imaging of peritoneal cancers using galactosamine-conjugated human serum albumin
Celeste A. S. Regino, Mikako Ogawa, Michelle Longmire, Nobuyuki Kosaka, Peter L. Choyke, Hisataka Kobayashi, ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 236, Aug. 2008
English, Summary international conference - Effects of lactate loading on brain glucose metabolism: Investigation with [18F]FDG-PET in conscious rats
Mikako Ogawa, Y. Ouchi, T. Fuchigami, T. Torizuka, M. Futatsubashi, Y. B. Jin, Y. Magata, Journal of Cerebral Blood Flow and Metabolism, 27, 13 Nov. 2007 - GMI社製動物用PET/SPECT/CT装置FXシステムの性能評価
間賀田泰寛, 小川美香子, 淵上剛志, 山口博司, 核医学, 44, 3, 315, 315, Oct. 2007
(一社)日本核医学会, Japanese - SYNTHESIS AND EVALUATION OF [C-11]EMMP AS A BRAIN NPY-Y1 RECEPTOR IMAGING AGENT FOR POSITRON EMISSION TOMOGRAPHY
M. Ogawa, K. Hatano, J. Abe, K. Ito, Y. Magata, JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS, 48, S94, S94, Jun. 2005
English, Summary international conference - SYNTHESIS OF 5-[C-11]ETHYL-A85380 ([C-11]5EA) AS A BRAIN NICOTINIC ACETYLCHOLINE RECEPTOR IMAGING AGENT FOR POSITRON EMISSION TOMOGRAPHY
M. Ogawa, S. Nishiyama, H. Tsukada, Y. Iida, H. Saji, Y. Magata, JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS, 48, S105, S105, Jun. 2005
English, Summary international conference - RADIOSYNTHESIS AND IN VIVO EVALUATION OF N- [C-11]-METHYLATED IMIDAZOPYRIDINE DERIVATIVES AS POSITRON EMISSION TOMOGRAPHY TRACER FOR PERIPHERAL BENZODIAZEPINE RECEPTORS
K. Sekimata, K. Hatano, M. Ogawa, J. Abe, Y. Magata, G. Biggio, M. Serra, G. Trapani, K. Ito, JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS, 48, S137, S137, Jun. 2005
English, Summary international conference - 99mTc標識抗LOX-1抗体の動脈硬化イメージング剤としての評価:99mTc標識アネキシンVとの比較
石野誠悟, 久下裕司, 向高弘, 高井希望, 小川美香子, 玉木長良, 久米典昭, 塩見雅志, 佐治英郎, 核医学, 42, 3, 2005 - Development of injectable O-15 oxygen and estimation of OEF in a transient ischemia–reperfusion rat model
Takashi Temma, Yasuhiro Magata, Hidehiro Iida, Mikako Ogawa, Takahiro Mukai, Yasuhiko Iida, Masashi Ueda, Junji Konishi, Hideo Saji, International Congress Series, 1264, 197, 201, 2004
Elsevier BV - Current Topics of Amyloid Beta Plaque Imaging
OGAWA Mikako, Radioisotopes, 52, 6, 315, 317, 15 Jun. 2003
日本アイソトープ協会, Japanese - [18F]FDG accumulation to the atherosclerotic vulnerable plaque: Correlation with infiltrated macrophage number.
M Ogawa, T Mukai, S Ishino, D Asano, N Teramoto, H Watabe, N Kudomi, M Shiomi, Y Magata, H Iida, H Saji, JOURNAL OF NUCLEAR MEDICINE, 44, 5, 189P, 190P, May 2003
English, Summary international conference - NBM破壊モデルラットを用いたアルツハイマー病早期核医学診断のための基礎的検討
小川美香子, 中川雅喜, 河嶋秀和, 飯田靖彦, 久下裕司, 清野泰, 間賀田泰寛, 佐治英郎, 日本薬学会年会要旨集, 123rd, 3, 2003 - Development of positron emitter labeled compounds and their application for biological estimation of therapeutic drugs.
Y Magata, M Ogawa, H Saji, JOURNAL OF PHARMACOLOGICAL SCIENCES, 91, 23P, 23P, 2003
English, Summary international conference - Age-related decline of dopamine transporters in F344/N rat striatum revealed by PET and [C-11]beta-CFT
K Hatano, M Suzuki, M Ogawa, Y Kawasumi, H Tsukada, K Ito, NEUROIMAGE, 16, 3, S35, S35, Jul. 2002
English, Summary international conference - A new strategy for rapid clinical imaging of rCMRO2, rCBF and rOEF using PET. Introducti.
H Iida, Y Miyake, T Hayashi, N Kudomi, M Ogawa, N Teramoto, KM Kim, H Oka, K Hayashida, JOURNAL OF NUCLEAR MEDICINE, 43, 5, 62P, 62P, May 2002
English, Summary international conference - Development and application of a GSO detector assembly for a continuous blood sampling system.
N Kudomi, E Choi, H Watabe, KM Kim, M Shidahara, M Ogawa, N Teramoto, E Sakamoto, S Yamamoto, H Iida, JOURNAL OF NUCLEAR MEDICINE, 43, 5, 229P, 229P, May 2002
English, Summary international conference - ペプチドの[18F]AcOFによる直接フッ素-18標識法の開発
小川 美香子, 籏野 健太郎, 川角 保弘, 伊藤 健吾, 大石 真也, 藤井 信孝, 川口 道也, 土井 隆一郎, 山本 幹夫, 味戸 慶一, 三宅 義徳, 飯田 秀博, 日本薬学会年会要旨集, 122年会, 3, 66, 66, Mar. 2002
(公社)日本薬学会, Japanese - αVβ3インテグリンをターゲットとした18F標識新規腫瘍イメージング剤の開発
小川 美香子, 籏野 健太郎, 伊藤 健吾, 川角 保広, 川口 道也, 土井 隆一郎, 大石 真也, 藤井 信孝, 核医学, 38, 5, 579, 579, Sep. 2001
(一社)日本核医学会, Japanese - Development of a novel central nicotinic acethylcholine receptor imaging agent: 5-(11)Cmethyl-A-85380.
Y Iida, M Ogawa, A Tominaga, T Mukai, Y Magata, H Saji, JOURNAL OF NUCLEAR MEDICINE, 42, 5, 250P, 250P, May 2001
English, Summary international conference - インスリン非依存性糖尿病モデルラットの心臓におけるnorepinephrine transporter機能の変化
清野泰, 河嶋秀和, 小川美香子, 飯田靖彦, 佐治英郎, 日本薬学会年会要旨集, 120th, 3, 2000 - Uncoupling between cortical glucose metabolism and blood flow after ibotenate lesion of the rat basal forebrain: a PET study
OGAWA M., Neurosci Lett, 204, 193, 196, 1996
Research Themes
- X線によるDrug Delivery Systemの構築
科学研究費助成事業
28 Jun. 2024 - 31 Mar. 2027
小川 美香子, 稲波 修
日本学術振興会, 挑戦的研究(萌芽), 北海道大学, 24K22102 - エネルギー代謝に着目した核医学イメージングによるがん微小環境評価
科学研究費助成事業
01 Apr. 2022 - 31 Mar. 2026
小川 美香子, 久下 裕司, 平田 健司, 鍛代 悠一
これまでに抗PD-1治療の初期段階でがん細胞の糖代謝能が亢進し、 [18F]FDGの集積が上昇することを示した。また、このがん細胞の糖代謝は免疫細胞の活性化により減少することも示した。しかしながら、これまで使用してきたB16F10モデルは、免疫細胞が少なく免疫細胞自体の評価が行えなかった。そこでより免疫原性が高いCT26を移植した担がんマウスモデルを用いて検討を行った結果、がん細胞と免疫細胞の糖代謝能が減少したにも関わらず、[18F]FDGの集積量は変化しなかった。この理由として、抗PD-1療法による腫瘍内の血液灌流の亢進が一因である可能性が考えられた。
そこで今年度、低酸素PETイメージング剤[18F]FMISOを用い検討を行った。 [18F]FMISO-PETによる低酸素イメージングでは変化は認められなかったものの、[18F]FMISO低集積の領域では免疫細胞および成熟した血管が多いことが示された。そこで、Pimonidazole染色による低酸素評価を行ったところ、PD-1群のがん組織全体、がん細胞および免疫細胞における低酸素状態の細胞の割合が有意に低いことが示された。また、治療早期の時点から腫瘍内に浸潤する免疫細胞が増加し、抗腫瘍免疫が活性化していることが示唆された。以上の結果から、抗PD-1療法は腫瘍体積に変化がない治療初期において免疫細胞の浸潤量を増加させ、腫瘍内の低酸素状態にある細胞の割合を減少させることが示された。
さらに、新規開発した乳酸代謝イメージング剤[18F]fluorolactateを用い検討を行った。インビトロでの検討では、より免疫原性が高いMC38細胞と比較して、CT26細胞への集積のほうが高かった。また、抗PD-1療法における代謝の変化を[18F]FDGと比較したが、腫瘍への集積に有意な差は認められなかった。
日本学術振興会, 基盤研究(B), 北海道大学, 23K24270 - エネルギー代謝に着目した核医学イメージングによるがん微小環境評価
科学研究費助成事業
01 Apr. 2022 - 31 Mar. 2026
小川 美香子, 平田 健司, 久下 裕司, 鍛代 悠一
日本学術振興会, 基盤研究(B), 北海道大学, 22H03009 - がん特異的糖鎖抗原を用いた小児がんに対する近赤外光線免疫療法の確立：前臨床モデル
科学研究費助成事業
01 Apr. 2022 - 31 Mar. 2025
長 祐子, 真部 淳, 小川 美香子, 樋田 泰浩, 植木 将弘, 中島 孝平
日本学術振興会, 基盤研究(C), 北海道大学, 22K07884 - PET imaging for cancer treatment inducing ferrotosis
Grants-in-Aid for Scientific Research
01 Apr. 2021 - 31 Mar. 2025
久下 裕司, 安井 博宣, 小川 美香子, 平田 健司, 水野 雄貴
近年、フェロトーシスと呼ばれる新しい細胞死の様式が報告され、フェロトーシスを誘導する薬剤が新たながん治療薬として注目されている。このフェロトーシスの進行には、トランスフェリン受容体1 (TfR1) が深く関与することが知られている。そこで本研究では、TfR1を標的とした新たなPETイメージング剤を開発し、フェロトーシス誘導剤の治療効果予測/判定に有効なイメージング技術を確立することを目的とする。
令和5年度は昨年度に引き続き、cystine dense peptideの1種であるTfRB1G3を母体としたPETイメージング剤の開発を進めた。TfRB1G3にHBED-CC (ガリウムに対するキレート試薬) を縮合した標識前駆体を合成し、67/68Ga標識体を作製した。作製した67Ga標識体を用いてsaturation binding assayを実施したところ、そのKD値は1.6 nMであり、TfR1への非常に高い親和性を示した。また、67Ga標識TfRB1G3をマウス血漿中で１時間インキュベートした後、HPLCを用いてその未変化体比率を評価したところ、90%以上の放射能が未変化体として存在し、生体内における高い安定性が示唆された。さらに、皮下腫瘍移植マウスを用いた体内分布試験を実施した結果、67Ga標識TfRB1G3はTfR1陽性腫瘍への高い集積 (8.6 %ID/g) を示し、その集積は過剰のTfRB1G3の同時投与で1.6 %ID/gまで減少した。これらの結果から、67/68Ga標識TfRB1G3がTfR1発現量を特異的かつ高感度に画像化する核医学イメージング剤として、有望な性質を有していることが示唆された。
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 23K21417 - PET imaging for cancer treatment inducing ferrotosis
Grants-in-Aid for Scientific Research
01 Apr. 2021 - 31 Mar. 2025
久下 裕司, 安井 博宣, 小川 美香子, 平田 健司, 水野 雄貴
近年、フェロトーシスと呼ばれる新しい細胞死様式が報告され、フェロトーシスを誘導する薬剤が新たながん治療薬として注目されている。このフェロトーシスの進行には、トランスフェリン受容体1 (TfR1) が深く関与することが知られている。本研究の目的は、TfR1の特異的イメージングを可能とする新たなPETイメージング剤を合成し、PETによるTfR1イメージングがフェロトーシス誘導剤の治療効果予測/判定やフェロトーシス誘導剤の開発に有効な手段となるか否かを明らかにすることにある。
本目的達成のため、これまでに主に新たなPETイメージング剤の合成検討、及びIn vitro細胞実験を行った。その結果、TfR1への親和性を有する7残基直鎖ペプチド (DT7) を母体とした68Ga標識プローブ（68Ga-DT7）が、T98G (TfR1高発現細胞株) に対してTfR1特異的に集積することを見出した。一方で、その集積量はやや低かったことから、分子内に2つのDT7ペプチドを有する2価DT7を新たに設計し、合成に成功した。しかし、68Gaで標識した2価DT7のT98Gへの集積量は予想に反して低かった。さらに、直鎖上のDT7ペプチドを環状化した環化ペプチドを合成し、T98Gへの集積量を評価したが、TfR1特異的集積量の向上には繋がらなかった。
上記検討結果から、TfR1への親和性がより高いリガンドを母体としたプローブを開発する必要性が示唆された。そこで、cystine dense peptideの１種でありTfR1との高い結合親和性を有するTfRB1G3を母体としたプローブの開発を開始した。
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 21H02858 - Development of photoimmunotherapy that not require external light irradiation
Grants-in-Aid for Scientific Research
09 Jul. 2021 - 31 Mar. 2024
花岡 宏史, 小川 美香子, 石岡 典子
光免疫療法は新たながん治療法として注目されており、臨床において優れた治療効果を示している。しかし光免疫療法においては、がんに対してどのように光を照射するかというのが一つの課題である。一方、放射性薬剤が放出するチェレンコフ光は、光免疫療法の光源として利用可能であると考えられる。そこで本研究では、光免疫療法に用いるのに適した新規放射性薬剤を開発することで、外部からの光照射を必要としないチェレンコフ光による新たな光免疫療法を確立することを計画した。
今年度はチェレンコフ光を利用した光免疫療法の基礎検討として、高エネルギーβ線放出核種であるイットリウム-90(90Y)を用いたチェレンコフ光の検出実験を行った。しかし用いた装置の検出感度が不十分であり、90Yから放出されるチェレンコフ光を検出するには至らなかった。現在、どのように検出を行うか検討中である。
一方、新規放射性薬剤の開発においては、新たな薬剤を設計し、合成に取りかかっている。90Y標識薬剤としては対してクリック反応を起こすテトラジンをリンカーを介してキレート剤に結合した化合物を、76Br標識体としてはBrチロシンを用いることとし、前駆体としてチロシンに対してリンカーを介してテトラジンを結合した化合物を用いる予定である。
またテトラジンとクリック反応するTrans-Cyclooctene（TCO）を結合した抗体とテトラジンを結合した分子が、生体内でクリック反応を起こすことは、マウスを用いた検討により確認することができた。
Japan Society for the Promotion of Science, Grant-in-Aid for Challenging Research (Exploratory), Kansai Medical University, 21K19459 - Ferroptosis imaging with PET: Challenge to assess vulnerability of atherosclerotic plaques
Grants-in-Aid for Scientific Research
09 Jul. 2021 - 31 Mar. 2024
久下 裕司, 安井 博宣, 小川 美香子, 横田 千晶, 水野 雄貴
動脈硬化病変の評価においては、早期治療を必要とする“破綻しやすいプラーク（不安定プラーク）”を的確に診断することが重要である。最近、鉄依存性酸化ストレスに起因するフェロトーシスと呼ばれる細胞死の様式が、動脈硬化の病態にも深く関与していることが報告された。本研究の目的は、フェロトーシス関連分子のPETイメージングにより、不安定プラークの診断が可能となるか検証することにある。
フェロトーシスの進行には、トランスフェリン受容体1 (TfR1) が深く関与することが知られている。令和3年度は、TfR1への高い結合親和性を有する直鎖ペプチド (DT7) を母体とした68Ga標識プローブ（68Ga-DT7）を合成し、in vitro実験条件下でTfR1イメージング剤としての有用性を評価した。その結果、68Ga-DT7は、TfR1特異的に集積したが、細胞集積量は十分ではなかった。そこで、細胞集積量の向上を目指してペプチドの多量体化や環状化などを実施したが、68Ga-DT7の細胞集積量を上回る誘導体の創成には至らなかった。
一方、不安定プラークにおけるフェロトーシスの関与をより多角的に評価するため、プラークにおける酸化ストレスを可視化できるプローブの合成と評価を開始した。合成した標識体は活性酸素種 (ROS)との反応によって錯体が崩壊し、酸化ストレスイメージング剤として機能する可能性が示された。
以上の検討結果から、TfR1への結合親和性がより高いリガンドの68Ga標識体を作製する必要性が示唆された。今後、cystine dense peptideの1種であるTfRB1G3の68Ga標識体を合成し、TfR1イメージング剤としての評価を行う。また、フェロトーシス関連分子のイメージングによる不安定プラークの多角的評価に向けて、酸化ストレスイメージング剤の開発も継続する。
Japan Society for the Promotion of Science, Grant-in-Aid for Challenging Research (Exploratory), Hokkaido University, 21K19433 - Development of photoimmunotherapy via O-glycans and siRNA delivery system using iRGD nanoparticles in lung cancer
Grants-in-Aid for Scientific Research
01 Apr. 2021 - 31 Mar. 2024
加藤 達哉, 櫻井 遊, 畑中 佳奈子, 小川 美香子, 樋田 泰浩, 畑中 豊
本研究はMUC1がん特異的糖鎖抗原のみを選択的に認識する新規モノクローナル抗体（MUC1-Tn抗体）と光感受性物質であるIR700との結合体を用いて、がん細胞のみを特異的に攻撃する新たな治療法を確立し、新規の肺がん治療法の開発を目指すものである。
今年度は、まず本研究の肝となるMUC1-Tn抗体の供給源である㈱医化学創薬と共同で研究をすすめ、MTAを締結し、本実験で想定される抗体量の確保に努め、動物実験まで含めた十分量の抗体を得ることに成功した。
さらに今年度は、研究実施計画に則り、まず今後in vitro実験およびin vivo実験に用いる予定のMUC1-Tn高発現の細胞株の選定を行った。乳癌細胞株であるT47DがMUC1-Tnが高発現していることが判明したが、その後21個の肺癌細胞株のセルブロックを作成し、抗MUC1-Tn抗体を用いて免疫染色を行った。うち2株（RERF-LC-KJ, H2228）に高発現が認められ、今後、in vitroおよびin vivo実験に使用可能と判断した。その他、陰性コントロールとしての細胞株も複数選定した。
また、実験遂行者はすでにIR700と抗MUC1-Tn抗体を合成する技術を習得しており、予備実験として、MUC1-Tn抗体とIR700の結合体を作成し、T47Dに導入後、FACSにて細胞膜表面に抗体が結合していることを確認した。また、タイムラプス顕微鏡でレーザー照射により導入細胞で細胞膜よりブレブが隆起し、細胞死に至ることを確認することができた。したがって今後肺癌細胞株を用いた本実験を開始できる状況にある。
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, 21K08876 - Establishment of near-infrared photoimmunotherapy targeting CD73 using mouse lung cancer model
Grants-in-Aid for Scientific Research
01 Apr. 2021 - 31 Mar. 2024
畑中 豊, 加藤 達哉, 小川 美香子, 畑中 佳奈子
がん微小環境において，低酸素状態下ではATPからAMPを介しアデノシンを生成する
CD39/CD73カスケード分子の発現が誘導され，さらにアデノシンはリンパ球上のA2受容体を介して免疫抑制状態を誘導することから，免疫チェックポイント阻害（ICI）療法に対し抵抗性を示す．
本研究は，先行研究として実施した非小細胞肺癌（NSCLC）の一部でCD73発現が亢進し，またPD-L1発現と相関する点に着目し，(a) NSCLC組織検体を用いたCD73およびPD-L1発現と腫瘍微小環境との関連性について検討し，次いで(b) ヒトおよびマウス肺癌細胞株を用いたCD73-IR700-Cのがん細胞への集積確認と治療効果のin vitro評価，および(c) ヒトおよびマウス肺癌細胞株の移植腫瘍モデルを用いたCD73抗体-IR700結合体（CD73-IR700-C）の腫瘍集積性の確認および近赤外線免疫療法（NIR-PIT）の抗腫瘍効果のin vivo評価を行う．
本年度は以下の課題に取り組んだ．肺扁平上皮癌症例を用いた組織マイクロアレイ（TMA）標本123例を用いた低酸素関連タンパクの臨床病理学的検討：CD73，PD-L1およびHIF-1a発現について検討したところ，先行研究同様，CD73とPD-L1発現間に有意な関連性（p=0.019）が認められ，またCD73とHIF-1a発現間にも関連傾向（p=0.0548）が観察された．これら３分子の生存解析においては，低発現群に比べ高発現群で，それぞれ有意な無再発生存期間（RFS）の短縮が認められ，さらにCD73高発現/HIF-1a高発現群ではさらに短縮した（p=0.0187）．
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, 21K07189 - 硬X線による化合物活性化を利用した新しいがん治療法の開拓
科学研究費助成事業
01 Apr. 2021 - 31 Mar. 2023
小川 美香子
日本学術振興会, 新学術領域研究(研究領域提案型), 北海道大学, 21H00158 - α線治療はなぜ効くのか？ーがん免疫から迫るー
科学研究費助成事業
28 Jun. 2019 - 31 Mar. 2022
小川 美香子, 東川 桂
最近、がん治療では免疫細胞の関与が重要であることが明らかとなってきている。そこで、飛程が長いβ線治療ではがん細胞の周囲にあるT細胞・樹状細胞などの免疫細胞を巻きこみ死滅させる可能性があるが、飛程が短いα線治療では放射標識薬剤が結合したがん細胞のみに影響を与えるのではないかと発想した。すなわち、標的化α治療ではがん免疫が活性化していることにより、大きな治療効果が現れているのではないかと考え、α線治療とがん免疫の関連について検討することを本研究の目的とする。
昨年度までに、還元型At-211を利用した新規標識法を開発した。本年度はさらに多くの化合物へ展開し、9種類の化合物の標識合成に成功した。また、樹脂を使った固相での標識合成も達成した。
また、I-131標識体の合成のため、I-125での事前検討を行った。さらに、昨年に引き続き、X線による外照射によるがん免疫の検討を行った。昨年は腫瘍が小さすぎたのと線量が高すぎたので腫瘍がほぼ消失してしまい、フローサイトメータなどによるアッセイがほとんど行えなかったので、今年度は腫瘍が100 mm3超えてから照射することとし、かつ線量を10 Gyから8 Gyに落とし検討を行った。照射開始日（Day0）とDay3にPD-1抗体を投与し、Day4およびDay10に安楽殺し、フローサイトメトリーにより免疫細胞の評価を行った。この結果、X線照射直後に抗腫瘍免疫を担うCD8 T細胞の減少が観察され、外照射により腫瘍組織内の免疫活性が一時的に低下することが示唆された。CD4 T細胞X線照射直後での変化は少ないものの、照射から1週間後では顕著に減少していた。CD4は免疫記憶などにも関与することからその減少は抗腫瘍免疫の減弱につながると考えられる。放射線照射により免疫原性が高まった際にPD-L1の発現が増加するとの報告があったが変化は認められなかった。
日本学術振興会, 挑戦的研究(萌芽), 北海道大学, 19K22587 - Elucidation of the Mechanism of Photoimmunotherapy Using Molecular Imaging and Development of New Drugs
Grants-in-Aid for Scientific Research
01 Apr. 2019 - 31 Mar. 2022
Ogawa Mikako
Photoimmunotherapy is a novel phototherapy for cancer that uses a drug with a light-sensitive dye IR700 conjugated to an antibody. In this study, PIT was evaluated using in vivo molecular imaging, which is the applicant's area of expertise. Furthermore, we aimed to improve versatility and applicability by developing longer wavelength and peptide drugs.
PET and ARG results suggested that PIT enhanced oxygen supply to the center of the irradiated tumor, thereby eliminating hypoxia. The small molecule drug GUL-IR700 was shown to have the potential to injure cells even through aggregate formation, although the 1O2 contribution was greater than that of antibody-IR700.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 19H03593 - Assessment of unstable plaque by PET, CT, and MRI combination
Grants-in-Aid for Scientific Research
01 Apr. 2018 - 31 Mar. 2021
Tamaki Nagara
Precise assessment of plaque characterization has recently been performed using various imaging modalities in order to identify unstable plaque. PET has been used for identifying active inflammation. CT provides precise assessment of macrocalcification with high spatial resolution images. Furthermore, MRI may identify lipid core and shear stress in the vessel walls.
We have performed immunohistochemical assessment for PET tracer uptake in experimental animal models. These experimental studies permit most suitable conditions for identifying unstable plaques using PET. The clinical studies have done to assess plaque characterization and identify unstable plaques with combined imaging of PET, CT, and MRI.
These experimental and clinical studied may permit most suitable non-invasive imaging for identifying unstable plaques and their tissue characterization in vivo.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Kyoto Prefectural University of Medicine, 18H02769 - 自己会合型環境応答性光音響イメージング剤の開発
科学研究費助成事業
01 Apr. 2018 - 31 Mar. 2020
小川 美香子
日本学術振興会, 新学術領域研究(研究領域提案型), 北海道大学, 18H04723 - Cancer therapy by Cerenkov radiation
Grants-in-Aid for Scientific Research
01 Apr. 2016 - 31 Mar. 2019
Ogawa Mikako
It is difficult to deliver light to deep tissue in human, due to scatter and attenuation of the light. In this study, we aimed to treat cancer by photoimmunotherapy in deep tissue, using Cerenkov luminescence resonance energy transfer (CRET) by PET probe.
It was confirmed that cell death occurs in the same way as excitation of the Q band in the near infrared region by excitation of the Soret band of IR700 molecules that can be excited by Cerenkov light. However, no cell death was observed using 18F-labeled antibody or antibody fragment. Thus, we tried to use X-ray excitation / ionization, and activation of photoreactive compounds was successfully observed.
Japan Society for the Promotion of Science, Grant-in-Aid for Challenging Exploratory Research, Hokkaido University, 16K15568 - Theranostics by combination with nuclear and optical methods
Grants-in-Aid for Scientific Research
01 Apr. 2016 - 31 Mar. 2019
Ogawa Mikako
Photo-immunotherapy (PIT) is a new cancer therapy using near-infrared light. In this research, we aimed to establish "Theranostics" method, which is a fusion technology of "diagnosis" and "therapeutics" of cancer by combining nuclear medicine and light technology. When the mouse tumor was illuminated, the fluorescence disappeared. PET imaging was performed before and after treatment in this mouse, decrease in [18F]FDG and [18F]FMISO was observed immediately after light irradiation before tissue damage observed. That is, it is suggested that the therapeutic effect can be diagnosed by PET.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 16H05382 - Vulnerability Assessment of Atherosclerosis by PET
Grants-in-Aid for Scientific Research
01 Apr. 2015 - 31 Mar. 2018
Tamaki Nagara
PET permits molecular imaging and quantitative assessment of vascular function. We performed quantitative assessment for experimental and clinical atherosclerosis by PET. FDG as a marker of macrophage and FMISO as a hypoxic marker showed altered glucose metabolism and hypoxic response in diabetic atherosclerosis in rabbits. The PET studies indicated reduced myocardial flow reserve (MFR) in relation to altered FFR in patients with coronary artery disease. In addition, impaired peripheral endothelial function was suggested by oscillometry which was correlated with coronary endothelial dysfunction in smokers. Furthermore, active cardiac sarcoidosis was identified by FDG-PET. Thus, PET permits identification of active atherosclerosis and quantitative assessment of vascular dysfunction. PET should play an important role for risk assessment and patient management in the near future.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), 15H04898 - A potential role of lymphatic vessels in drug delivery system
Grants-in-Aid for Scientific Research
01 Apr. 2014 - 31 Mar. 2018
Hirakawa Satoshi
Tumor lymphagiogenesis is promoted by stepwise process although it has not been fully elucidated. Among tumor microenvironment, tumor-associated angiogenesis has been well characterized. Furthermore, it is well understood that vascular system plays a key role in drug delivery during chemotherapy. Therefore, in the present study, we aimed to show a significant role of lymphatic vessels in drug delivery as well as clearance during the therapy. Lymphatic vessels show persistent enlargement during inflammation, leading to reduced draining function. Furthermore, tumor-associated lymphatic vessels are known to show the reduction of flow in tumor progression. Here we subjected transgenic mice which express green fluorescent protein under the Prox1 promoter which is specifically activated in lymphatic endothelial cells, and successfully found that fluorescence-labeled dextran was absorbed by the lymphatic capillary vessels.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hamamatsu University School of Medicine, 26293257 - Imaging and Drug Delivery to Sentinel Lymph Node by Using All-In-One Dendrimers
Grants-in-Aid for Scientific Research
01 Apr. 2014 - 31 Mar. 2017
Kojima Chie, KONDO Eisaku
Because cancer is a leading cause of death in Japan, development of imaging technology for cancer diagnosis and drug delivery systems for cancer therapy are crucial. Dendrimers are synthetic macromolecules with highly controllable structures, which are potent multifunctional imaging agents and drug carriers. The detection of the sentinel lymph node (SLN), the first lymph node draining tumor cells, is important in cancer diagnosis and therapy. First, the optimal dendrimer structure for SLN imaging was investigated. Carboxyl-terminal dendrimers of greater than G4 were mostly located in the SLN. SLN detection was successfully performed by nuclear medicinal imaging and fluorescent imaging using these dendrimers. Finally, triply functional dendrimers with tumor targeting activities, antitumor effects and detectable probes were prepared.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Osaka Prefecture University, 26410227 - Cerenkov luminescence imaging using PET probes
Grants-in-Aid for Scientific Research
01 Apr. 2013 - 31 Mar. 2016
OGAWA Mikako
Optical imaging has advantages in its easy-to-use feature. But, in general, optical imaging probes have large molecular weight and it is difficult to do brain imaging. On the other hands, PET imaging is superior in quantitative analysis, and many brain imaging probes are available. It is now of great interest performing cerenkov luminescence imaging (CLI) by PET probes. In this study, we evaluated the feasibility of CLI for the analysis of brain function.
In [18F]FDG studies, there was a good relationship between the radioactivity and CLI signal in brains. [11C]raclopride and [11C]b-CFT imaging was also successful, and luminescence in the striatum was decreased by haloperidol (D2 receptor ligand) treatment until 30 min post injection of [11C]raclopride. [11C]b-CFT produced more clearer images than [11C]raclopride. Although the quantitativity is inferior to PET imaging, it is revealed that CRI can be applied for brain function analysis in mice.
Japan Society for the Promotion of Science, Grant-in-Aid for Challenging Exploratory Research, 25670528 - development of a novel imaging probe for alteration of mitochondria function based on cancer therapy
Grants-in-Aid for Scientific Research
01 Apr. 2013 - 31 Mar. 2016
Magata Yasuhiro, SAKAHARA HARUMI, SUZUKI CHIE, OGAWA MIKAKO
For the purpose prediction of therapeutic effect and early judgment of the therapy, we developed a novel imaging probe to estimate mitochondria function which relates "apoptosis", or "oxygen". We have already obtained the radioiodinated labeled compound I-125-DPP which accumulates to cells depending on their mitochondrial membrane potential. Unfortunately, this compound was excreted from the cells by P-glycoprotein (P-gp) just after uptake in the cells. In order to improve this problem, we designed and synthesized a new drug I-125-DESP including a styilbene group which is an inhibitor against P-gp. I-125-DESP was uptake 6.7 times higher into cancer cells compared with I-125-DPP. Moreover, almost I-125-DESP was not excreted from the cancer cells. These results indicate POC of the drug design of this compound. Then, we performed in vivo imaging studies with an animal SPECT machine. Unfortunately, high uptake of radioactivity in the liver was observed and tumor could not visualized.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hamamatsu University School of Medicine, 25293262 - PET imaging probes for detection and evaluation of atherosclerotic plaques
Grants-in-Aid for Scientific Research
01 Apr. 2012 - 31 Mar. 2016
OGAWA Mikako
Disruption of atherosclerotic plaques and the following thrombus formation is currently recognized as the primary mechanism of myocardial and cerebral infarctions. In this study, we compared PET imaging agents, [18F]FDG, [18F]FMISO, [18F]NaF, [11C]Choline, [11C]PK11195, using WHHL rabbit in same animals.
[18F]FDG accumulated into atherogenic M1 macrophges, but SN ratio was not very high. [18F]NaF showed the highest SN ratio, and small region was clearly visualized. Macrophage accumulation was seen with [11C]Choline, however, the signal from the heart and liver disturbed the detection with PET. [11C]PK11195 distribution was different from [18F]FDG, and in some animals, the plaque was not detected due to the high heart uptake. [18F]FMISO did not show significant signal around the atherosclerotic regions.
Japan Society for the Promotion of Science, Grant-in-Aid for Young Scientists (A), 24689049 - In vivo imaging of the activity of ganma-secretase for amyloid production in Alzheimer's disease
Grants-in-Aid for Scientific Research
01 Apr. 2011 - 31 Mar. 2014
OUCHI Yasuomi, UEKI Takatoshi, OGAWA Mikako, MAGATA Yasuhiro
Because it has been shown that the degree of beta-amyloid deposition in the Alzheimer's brain does not correlate with the deterioration of cognitive function, we aimed to examine the activity of ganma-secretase that regulates the production of beta-amyloid in vivo. The MRI probe that was designed to emit signals in high-magnetic field MRI worked in the in vitro setting failed to give enough NMR signals in the in vivo measurement, suggesting that a probe with a high permeability for cells and with a large signal-emitting power would be desirable.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hamamatsu University School of Medicine, 23390287 - development of a novel imaging method for cancer therapy based on alteration of mitochondriafunction
Grants-in-Aid for Scientific Research
2010 - 2012
MAGATA Yasuhiro, SAKAHARA Harumi, MATSUSHIMA Yoshitaka, OGAWA Mikako, TAKASHIMA Misato
For the purpose of selection of cancer therapy, prediction of therapeutic effectandearlyjudgment of the therapy, weexplored development of a novel method to estimate mitochondria function which relates "apoptosis", or "oxygen". We obtained a radioiodinated labeled compound IDPP which accumulatesto a cell depending on mitochondrial membrane potential. On the other hand, the relationship between photodynamic therapy and alteration of cell function after PDT was estimated usinguptake value of FDG and MIBI as a marker. High PDT therapeuticeffect isexpected in case of high FDG uptake in tumor cells. And it was indicated thatthe decreasing ratio of MIBI uptake linearly relatedto PDT effect.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hamamatsu University School of Medicine, 22390232 - Development of a molecular imaging probe for vulnerable plaque imaging
Grants-in-Aid for Scientific Research
2009 - 2011
OGAWA Mikako
The rupture of atherosclerotic vulnerable plaques and the subsequent formation of thrombi are the main factors responsible for myocardial and cerebral infarctions. Macrophage infiltration is characteristics for atherosclerotic vulnerable plaques. Macrophages recognize phosphatidylserine(PS) that is exposed on the cell surface of the apoptotic cells to phagocytize these cells. In this study, we prepared PS liposomes for detection of vulnerable plaques. As a result, the atherosclerotic region was detected by this imaging probe.
Japan Society for the Promotion of Science, Grant-in-Aid for Young Scientists (B), Hamamatsu University School of Medicine, 21791181 - Development of novel CT contrast agents with long retention in the vessel
Grants-in-Aid for Scientific Research
2009 - 2011
SAKAHARA Harumi, MAGATA Yasuhiro, YAMAGUCHI Hiroshi, FUCHIGAMI Takeshi, OGAWA Mikako, KOJIMA Chie, SAKAI Toshihiro, TAKASHIMA Misato
The aim of this study is to develop novel CT contrast agent with a longer retention in blood in order to visualize vascular structure in a target tissue or angiogenesis of tumor. For this purpose, we use iodine or gold as a contrast element and human serum albumin or dendrimer modified with PEG as a carrier compound. Iodine modified agent showed a less enhancement effect in vivo because of its instability in blood. Gold modified agent showed a longer enhancement effect in vivo in comparison with a commercially available iodine contrast agent.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hamamatsu University School of Medicine, 21390343 - Elucidation of biological basis of autism as fatty acid metabolic disease
Grants-in-Aid for Scientific Research
2009 - 2011
MATSUZAKI Hideo, ZAIMA Nobuhiro, IWATA Keiko, OGAWA Mikako, TSUJII Masatsugu, SETOU Mitsutoshi, TSUCHIYA Kenji, ITOH Hiroaki, MAGATA Yasuhiro
In this project, we were focusing on impaired Very Low Density Lipoprotein (VLDL) lipid fraction in serum of individuals with autism. Then, we examined the serum levels of fatty acid composition, autistic animal models based on the lipid profile, imaging analyze and a novel therapy method of autism by using the autistic animal model. To identify causal fatty acid of VLDL-specific lipid profile in autism, we analyzed fatty acid composition by GC-MS, which resulted in impairment of some fatty acids including omega-6. Next, we identified that CD38KO mice showed impairment of VLDL fraction and omega-6 fatty acid like autistic human subject, and found that feeding challenge of omega-6 fatty acid could rescue impairment of social recognition behavior in CD38KO mice immediately after birth. In VLDL Receptor transgenic rat (VLDLR-Tg), we examined behavior test and found that the rat showed hyperactivity and an entire impairment of arachidonic acid distribution in tissues of VLDLR-Tg.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research on Innovative Areas (Research a proposed research project), 21200014 - 動脈硬化病変に生じる不安定プラークの検出に有用な核医学イメージング剤に関する検討
科学研究費助成事業
2007 - 2008
小川 美香子
最近、内臓脂肪の蓄積、高血圧、高血糖、高脂血症を特徴とする『メタボリックシンドローム』が、心筋梗塞や脳梗塞といった動脈硬化性疾患の発症要因となるマルチプルリスクファクター症候群として提唱され、適切な対策が求められている。この動脈硬化病変に生じる不安定プラークは、プラークの破綻、血栓形成、血管内腔の狭窄・閉塞という一連の病態を引き起こし、動脈硬化性疾患発症の原因となる。本研究では不安定プラークの検出に有用な、核医学イメージング剤に関する検討を行うものである。
これまでに我々は、[^<18>F]フルオロデオキシグルコース([^<18>F]FDG)が不安定プラークに浸潤するマクロファージの数に応じて集積することを報告してきた。そこで本年度は不安定プラークにおけるマクロファージの成熟段階に応じて[^<18>F]FDGの集積量が変化するかより詳細な検討を行った。すなわち、泡沫化する前のマクロファージとacLDLを添加することにより泡沫化させたマクロファージを培養し、それぞれへの[^<18>F]FDGの取り込み量を検討した。この結果、泡沫化12,24,48時間後すべてにおいて、泡沫化による影響は認められなかった。なお、マクロファージはacLDL添加後48時間で成熟した泡沫細胞となる。本検討結果は、[^<18>F]FDGでは不安定プラークの詳細な進展過程を追跡できないことを示すものであり、不安定プラークの進展過程で変化するマクロファージ表面抗原などを認識するような、新たなイメージング剤開発の必要性が示唆された。
日本学術振興会, 若手研究(B), 浜松医科大学, 19790865 - Development of novel evaluation system and radiopharmaceutical for prediction of tumor treatment effect ; especially oxygen effect of tumor therapy
Grants-in-Aid for Scientific Research
2005 - 2007
MAGATA Yasuhiro, SAKAHARA Harumi, OGAWA Mikako, HIRANO Toru, OHISHI Shinya, TSUKADA Hideo
The tumor treatment by radiation therapy or photo dynamic therapy (PDT) is limited by several biological factors such as tumor size, angiogenesis surrounding the tumor, blood flow. Especially, it is well known that oxygen concentration in the tumor circumstance affects on these therapies and the success rate decreases in the anoxia region. Although many researches have been performed concerning the oxygen effect, it is difficult to generalize the effect by clinical category of the tumor due to a large individual variation. Therefore, it is expected that prediction of the tumor therapy is useful for decision making of therapy planning or prognosis by the therapy. On these basis, we laid a plan to establish a novel evaluation system for prediction of tumor therapy by nuclear medicine technique in this project.
An evaluation system of oxygen concentration in the tumor in vivo was established using an oxymap. PDT therapy is strongly affected by oxygen concentration in the circumstance of the tumor. We selected a novel compound for PDT therapy from a chemical compound library by in silico estimation and confirmed that this compound irradiates a single state oxygen. Because In vitro experiments indicated that this compound kills tumor cells by laser irradiation, this compound or this structure is expected to be a key compound for a new PDT drug. In order to synthesize a novel peptide imaging agent labeled with a positron emitting nuclide, automatic synthesis system of F-18-SFB was established. GPR54 has been reported to relate tumor metastasis ability. We achieved application of this labeling probe to F-18-TOM80 which binds to GPR54. Moreover, consecutive SPECT and PET imaging method was established using a small animal trimodality imaging system which was installed in 2006. Combination of these results will be useful for tumor imaging study in the future.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hamamatsu University School of Medicine, 17390331 - Studies on radiopharmaceuticals with mitochondria membrane potential dependent tumor accumulation
Grants-in-Aid for Scientific Research
2005 - 2007
SAKAHARA Harumi, MAGATA Yasuhiro, OGAWA Mikako
It is well known that lipophilic cation radiopharmaceuticals such as T1-201 or Tc-99m-MIBI (MIBI) accumulate in some tumors and they are useful for tumor diagnosis. Both T1-201 and MIBI are currently used for myocardial blood flow scintigraphy. The uptake mechanism and kinetics in myocaridium cells have been reported to be different in these two radiopharmaceuticals. According to these reports, almost MIBI in the cells exist in the mitochondria fraction and the uptake of MIBI by myocardium cells depends on mitochondria membrane potential. Actually, the membrane potential of the myocardium is higher than that of other organs. In addition, the mitochondria membrane potential of some tumor cells is higher than that of normal cells_ It is expected that MIBI accumulates in the tumor cells depending on the membrane potential. On these basis, the uptake kinetics and patho-physiological studies of such cationic radiopharmaceuticals in the tumor cells was evaluated using in vitro cell culture experimental system in this research.
First of all, we prepared some tumor cell lines for in vitro experiments. Relative mitochondria membrane potential of these cells was evaluated with JC-1 and a large variation of the membrane potential was indicated. In in vitro experiments, a high relationship between the membrane potential and MIBI uptake in the tumor cells was observed. In addition, similar relationship was shown in case of FDG. Because mitochondria membrane potential relates to the activity of energy metabolism, these results suggested that the uptake of both compounds can be used as index of the tumor cells activity. Next, we perforthed MIBI and FDG uptake studies in the tumor cells after photo dynamic therapy (PDT). About 50 % decrease per cell at 1-3 hours post PDT irradiation was observed in only MIBI uptake. It is suggested this phenomenon is derived from the alteration of mitochondria function because of apoptosis induced by PDT. This discrepancy between MIBI and FDG uptake interests us for diagnosis of tumor cell condition after therapy.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hamamatsu University School of Medicine, 17390330 - 神経細胞選択的なエネルギー代射活動イメージング法の開発
科学研究費助成事業
2005 - 2006
小川 美香子
脳循環障害や神経変性疾患において、生理機能を保った神経細胞を特異的に描出することが、適切な治療や病態解明のために重要である。脳には神経細胞のほか、その約10倍ものグリア細胞が存在する。よって、神経細胞選択的なエネルギー代謝イメージング法を開発するためには、神経細胞特異的なエネルギー基質を標的にする必要がある。
これまでに我々は、脳スライスのイメージングシステムを用い、脳の活動時には神経細胞はブドウ糖だけでなくグリア細胞で作られた乳酸も利用していることを見いだした。そこで、乳酸代謝を画像化する核医学イメージング剤を用いれば、神経細胞の活動を非侵襲的に描出することができると考え、[^<18>F]L-fluorolactateの合成・利用を検討してきた。
本年度は、in vivoで検証することとし、脳エネルギー源としての乳酸の役割について[^<18>F]FDG-PETを指標とし検討を行った。20匹のラットを麻酔群、無麻酔群に分け、各群をさらに乳酸投与群、コントロール群に分け(n=5)、[^<18>F]FDG(7.4MBq)を投与後45分間、動物用PET装置にてdynamic PET撮像を行った。得られた画像から速度定数(K1,k2,k3,k4)を求め、CMRglcを計算した。無麻酔群において、乳酸の投与によりCMRglcが有意に上昇した(乳酸投与群:55.1μmol/100g/min、コントロール群:39.7μmol/100g/min)。一方、麻酔群においては乳酸投与による影響は観察されなかった(乳酸投与群:37.1μmol/100g/min、コントロール群:35.3μmol/100g/min)。さらに、無麻酔群においてk3は上昇傾向が認められた。
神経細胞がグルコースの代わりとしてエネルギー源に乳酸を利用するならば、神経細胞の活動が活発な無麻酔群においては、乳酸負荷によりグルコース利用能が低下することとなる。しかしながら、本検討では無麻酔群においてk3およびCMRglcの上昇が観察された。乳酸が糖代謝を活性化する原因について、乳酸の取り込み阻害剤を用いて現在さらに検討を進めている。
日本学術振興会, 若手研究(B), 浜松医科大学, 17790854 - 統合失調症の定量的評価を目的とする分子イメージング法の開発研究
科学研究費助成事業
2005 - 2006
間賀田 泰寛, 小川 美香子, 塚田 秀夫
近年、アルツハイマー病などの神経変成疾患では、臨床症状だけではなく、神経伝達物質やその受容体などの機能分子の変化を核医学の手法を用いて捉えることよる定量的評価が行われている。精神疾患である統合失調症においても死後脳を用いた研究により、ニコチン受容体α7サブタイプ(α7 nAChR)の関与が示唆されているが、現在α7 nAChRを非侵襲的に捉えるイメージング剤は無く、生体内での変化を画像化することはできない。そこで、α7 nAChRの核医学イメージング剤の開発を試みることとした。
17年度、azabicyclo環構造を有する放射性ヨウ素標識体I-TSAを開発し、ラット脳ホモジネートを用いてα7 nAChRへの親和性を検討したところ、Ki値は0.54nMとなり高い親和性を持つことが示されるとともに、高い放射化学的収率で放射性ヨウ素標識体の合成にも成功した。しかしながら、マウス体内動態を検討したところ、高い脳への取り込み、特に受容体の多い海馬からの消失が遅いなど、特徴的な動態を示したが、非放射性のI-TSAの同時投与により非特異的結合が高いことが示唆され、α7 nAChR in vivoイメージング剤として適さないことが示された。そこで18年度は同じくazabicyclo環構造を有する2-amino-5-bromo-benzoic acid 1-azabicyclo[2.2.2]oct-3-yl ester (BrQAA)およびその誘導体を開発した。BrQAAについてα7 nAChRへの親和性を検討したところ、Ki値は約500nMとそれほど高い値は示さなかった。しかしながらその他の誘導体における親和性の検討の結果より、azabicyclo環の窒素原子がα7 nAChRへの親和性を維持するために重要であることが見出され、今後の誘導体開発に重要な知見を与えることが出来た。今後更に、azabicyclo環構造を基本とする誘導体の開発を行っていく予定である。
日本学術振興会, 萌芽研究, 浜松医科大学, 17659364 - 神経細胞選択的なエネルギー代謝イメージング法の開発
科学研究費助成事業
2002 - 2004
小川 美香子
脳循環障害や神経変性疾患において、生理機能を保った神経細胞を特異的に描出することが、適切な治療や病態解明のために重要である。脳には神経細胞のほか、その約10倍ものグリア細胞が存在するといわれており、特にグリア細胞の一種であるアストロサイトの脳エネルギー代謝における役割が注目されている。よって、神経細胞選択的なエネルギー代謝イメージング法を開発するためには、神経細胞特異的なエネルギー基質を見いだし標的にする必要がある。
前年度までに、生きた脳スライスの経時的イメージングシステムを用い、脳の活動時には神経細胞はグルコースだけでなくグリア細胞で作られた乳酸も利用していることを見いだした。このことは、乳酸代謝を画像化する核医学イメージング剤を用いれば、神経細胞の活動を非侵襲的に描出することができる可能性を示すものである。そこで、ポジトロン断層撮像法(PET)によるイメージングが可能であり、TCAサイクルの途中までしか代謝されないことが予想される[^<18>F]L-fluorolactateの合成を試みた。生体で利用可能なL体を立体選択的に合成する必要があるため、[^<18>F]pyruvateから乳酸脱水素酵素を用いて合成することを計画し、まず、[^<18>F]pyruvateの合成を試みた。サイクロトロンより得られる[^<18>F]KFを前駆体のbromopyruvate methylesterに反応させたが、前駆体が標識条件下で不安定であった。そこで、[^<18>F]KFを[^<18>F]FCH_2Brへ変換したのち、酵素反応により[^<18>F]fluoroalanine,[^<18>F]fluoropyruvate,[^<18>F]lactateへと変換させる経路をみいだし、標識合成を行った。さらなる条件検討を行うことにより、[^<18>F]lactateによるPETでの乳酸代謝イメージングが可能になると思われる。
日本学術振興会, 若手研究(B), 浜松医科大学, 14770486
