2023 Fiscal Year Final Research Report

Development of a radioactive probe targeting the cell cycle regulatory factor CDK2

Research Project

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Project/Area Number	17K10369
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Radiation science
Research Institution	Health Sciences University of Hokkaido
Principal Investigator	Kitaura Hirotake 北海道医療大学, 薬学部, 准教授 (10281817)
Co-Investigator(Kenkyū-buntansha)	大倉一枝北海道医療大学, 薬学部, 教授 (60094827) 大島伸宏北海道医療大学, 薬学部, 助教 (80508648) 久下裕司北海道大学, アイソトープ総合センター, 教授 (70321958) 東川桂北海道大学, アイソトープ総合センター, 助教 (10756878) 水野雄貴北海道大学, アイソトープ総合センター, 助教 (90805194)
Project Period (FY)	2017-04-01 – 2024-03-31
Keywords	がんのイメジング / CDK2 / サイクリン依存性キナーゼ / 細胞周期制御因子
Outline of Final Research Achievements	We developed a cancer imaging diagnostic radiotracer targeting the cell cycle regulatory factor CDK2 protein, which exhibits high activity in various types of cancer. We designed, synthesized, and evaluated novel CDK2-binding inhibitory compounds, leading to the identification of a promising compound (I-KAN). I-KAN demonstrated potent CDK2 inhibition activity (IC50 = 0.096 μM) and proliferation suppression activity in A431 cells (CC50 = 1.8 μM). Cellular uptake of 125I-KAN in A431 cells showed a 500% dose/mg protein increase after 60 minutes. We conducted Western blot analysis and cellular uptake experiments using various cancer cell lines, and found that the gastric cancer cell line MKN45, which exhibits higher CDK2 expression, is optimal for establishing a xenograft mouse model for our cancer imaging studies.
Free Research Field	放射性医薬品
Academic Significance and Societal Importance of the Research Achievements	がんの画像診断にて広汎に使用されている18F-FDGは、糖代謝の激しい脳や肝臓等では診断が困難な状況が見られる。そこで、CDK2のようながんの細胞増殖の激しさを指標とする診断薬を開発できれば、このような臓器内における腫瘍において画像診断の精度が向上する可能性があり、学術的及び社会的意義が高いと考える。