Development of the PET imaging probe targeting Fibroblast Growth Factor Receptor
| 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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Report
(4 results)
Research Products
(30 results)
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[Journal Article] 18F-Labeled PSMA-Targeted Radiotracers: Leveraging the Advantages of Radiofluorination for Prostate Cancer Molecular Imaging.2020
Author(s)
Rudolf A. Werner, Constantin Lapa, Sara Sheikbahaei, Takahiro Higuchi, Frederik L. Giesel, Spencer Behr, Alexander Drzezga, Hiroyuki Kimura, Andreas K. Buck, Martin G. Pomper, Michael A. Gorin, Steven P. Rowe.
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Journal Title
Theranostics
Volume: 10(1)
Issue: 1
Pages: 1-16
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Initial clinical evaluation of PET/CT with 18F-FSU-880 targeting prostate-specific membrane antigen.2019
Author(s)
Tsuneo Saga, Yuji Nakamoto, Takayoshi Ishimori, Takahiro Inoue, Yoichi Shimizu, Hiroyuki Kimura, Shusuke Akamatsu, Takayuki Goto, Hiroyuki Watanabe, Kosuke Kitaguchi, Masao Watanabe, Masahiro Ono, Hideo Saji, Osamu Ogawa, Kaori Togashi.
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Journal Title
Cancer Science
Volume: 110 (2)
Issue: 2
Pages: 742-750
DOI
Related Report
Peer Reviewed
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[Journal Article] PET probe detecting non-small cell lung cancer susceptible to epidermal growth factor receptor tyrosine kinase inhibitor therapy2018
Author(s)
Akira Makino , Anna Miyazaki , Ayaka Tomoike , Hiroyuki Kimura , Kenji Arimitsu , Masahiko Hirata , Yoshiro Ohmomo , Ryuichi Nishii , Hidehiko Okazawa , Yasushi Kiyono , Masahiro Ono , Hideo Saji
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Journal Title
Bioorganic & Medical Chemistry
Volume: 26
Issue: 8
Pages: 1609-1613
DOI
Related Report
Peer Reviewed
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[Journal Article] 18F-Labeled Pyrido[3,4-d]pyrimidine as an Effective Probe for Imaging of L858R Mutant Epidermal Growth Factor Receptor.2017
Author(s)
Hiroyuki Kimura, Haruka Okuda, Masumi Ishiguro, Kenji Arimitsu, Akira Makino, Ryuichi Nishii, Anna Miyazaki, Yusuke Yagi, Hiroyuki Watanabe, Ikuo Kawasaki, Masahiro Ono, and Hideo Saji
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Journal Title
ACS Med Chem Lett.
Volume: 8
Issue: 4
Pages: 418-422
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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