| Project/Area Number |
17K10377
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Radiation science
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| Research Institution | Kyoto Pharmaceutical University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 繊維芽細胞増殖因子受容体 / PETプローブ / 繊維芽細胞増殖因子受容体1 / イメージングプローブ / SPECT / PET / 分子イメージング / I-123 / PET/SPECT分子イメージングプローブ / 放射線科学 / 放射性医薬品 |
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| Outline of Final Research Achievements |
Fibroblast Growth Factor Receptor 1 (FGFR1), known as a kind of tyrosine kinase receptor, is suggested that it promotes exacerbation of certain tumors. This research contains a drug design, synthesis, and evaluation of a new PET probe targeting FGFR1. In vitro kinase assay, nonradioactive 9 showed inhibitory activity to FGFR1 (IC50 = 172.6 nmol/L). In vivo biodistribution study, [18F]9 showed high accumulation and high retention to FGFR1 amplification tumor (3.23% dose/g). On the other hand, high blood retention of RI was observed (2.92% dose/g), which will be a cause of high background. In conclusion, though some improvements for high hydrophilicity or low protein binding rate are necessary, [18F]9 is the first compound as FGFR1-targeting nuclear medicinal imaging probe, and [18F]9 provide beneficial information to FGFR1 imaging in the future.
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| Academic Significance and Societal Importance of the Research Achievements |
これまでに、FGFRを標的としたPET/SPECT分子イメージングプローブの開発は報告が無く、本プローブ開発は独創的な研究であると考えられる。開発したプローブを用いがん化のメカニズム、薬剤耐性へのメカニズムを解明し、遺伝子情報を含んだ新規核医学診断法の開発、さらに分子標的薬の開発への効率的なワークフローの構築へと繋げることが出来ると考えている。また、FGFRを標的とした分子標的薬の開発が世界的に進められており、本研究で得られた成果を創薬に応用することも可能である。
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