| Project/Area Number |
16K19799
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Radiation science
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2018: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 核医学 / 低酸素 / 質量イメージング / PET / 2-nitroimidazole / イメージング / 放射線 / 薬学 / 癌 |
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| Outline of Final Research Achievements |
18F-FMISO has been used for hypoxia imaging of PET. However, its accumulation mechanism is still unclear because of its difficulty in distinguishing the metabolic states of FMISO in tumor by conventional radio isotope analysis methods. To reveal it, we performed in vitro and ex vivo studies in combination with imaging mass spectrometry (IMS).
In the IMS study, the amino-FMISO conjugated with glutathione (amino-FMISO-GS) showed a closely similar distribution pattern to autoradiography. In the cellular uptake study of FMISO, FaDu cells (high glutathione level) showed a higher radioactivity level compared with T24 cells (low glutathione level), and the levels of the amino-FMISO-GS in FaDu cells were higher than those in T24 cells in hypoxic condition. Our study suggests that FMISO is accumulated in hypoxic cells by the process of glutathione conjugation following reductive metabolism. Its accumulation might depend on glutathione levels in the cells as well as hypoxic condition.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究にて得られた知見は2-nitroimiedazole系イメージング剤の低酸素領域への集積メカニズム解明に大きく寄与するものであり，今後の新規低酸素イメージング剤の研究開発において新たな指標となりうることが期待される。また、GSTやMRP1を競合阻害する治療薬も報告されており、amino-FMISO-GSの生成および細胞外排泄において競合阻害する可能性があることから、これらの薬剤を併用時におけるFMISO-PET診断において、偽陽性・偽陰性診断を引き起こす可能性を示唆しており、今後のFMISO-PET診断に影響を与えるものと考えられる。
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