2016 Fiscal Year Final Research Report

Development of fluorine-18 labeled 4DST derivatives for clinical use

Research Project

PDF

Project/Area Number	25293271
Research Category	Grant-in-Aid for Scientific Research (B)
Allocation Type	Partial Multi-year Fund
Section	一般
Research Field	Radiation science
Research Institution	Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology
Principal Investigator	Toyohara Jun 地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究副部長 (50425659)
Co-Investigator(Kenkyū-buntansha)	窪田和雄一般財団法人脳神経疾患研究所, PETセンター, その他 (40161674) 木村裕一近畿大学, 生物理工学部, 教授 (60205002)
Co-Investigator(Renkei-kenkyūsha)	ISHIWATA Kiichi 一般社団法人脳神経疾患研究所, 南東北創薬・サイクロトロン研究所, 所長 (50143037) ISHII Kenji 地方独立行政法人東京都健康長寿医療センター, 東京都健康長寿医療センター研究所, 研究部長 (10231135) ODA Keiichi 北海道科学大学, 保険医療学部, 教授 (70224235) SAKATA Muneyuki 地方独立行政法人東京都健康長寿医療センター, 東京都健康長寿医療センター研究所, 研究員 (00403329) NARIAI Tadashi 東京医科歯科大学, 医学部付属病院, 准教授 (00228090)
Project Period (FY)	2013-04-01 – 2017-03-31
Keywords	核医学 / PET / 放射性医薬品
Outline of Final Research Achievements	The thymidine derivative 11C-4DST has the potential to visualize in vivo DNA synthesis rates with positron emission tomography (PET). To expand the use of 4DST needs the fluorine-18 version of this compound. In this study, we tried to synthesize the 18F-4DST analogues for practical use of DNA synthesis imaging. The three candidates were selected. The fluoromethyl version of 4DST was not stable and cannot obtained as an purified form. The fluoroethyl version of 4DST can be labeled with using N3-Boc-3',5'-di-O-tolyl-5-tosyloxyethane precursor. However, biodistribution studies did not show tumor selective uptake. The 5-fluoro version of 4DST could be labeled by 18F anion with Cu-mediated nucleophilic fluorination of tin-precursor. However, the yields were very low. The acute toxicity studies indicate 5-fluoro-4DST is acceptable as PET drug for human use. In contrast, 5-fluror-4DST has mutagenic activity in E. Coli as indicated by the Ames study.
Free Research Field	放射性医薬品科学