一种靶向DAT的氘代正电子探针的制备与表征  

Preparation and Characterization of A Deuterated Positron Probe Targeting DAT

作　　者：胡潜岳 唐婕 方毅 刘春仪 陈正平 HU Qianyue;TANG Jie;FANG Yi;LIU Chunyi;CHEN Zhengping(School of Pharmacy,Nanjing Medical University,Nanjing 211166,China;Key Laboratory of Nuclear Medicine,National Health Commission,Jiangsu Atomic Medical Research,Jiangsu Key Laboratory of Molecular Nuclear Medicine,Wuxi 214063,China)

机构地区：[1]南京医科大学药学院,江苏南京211166 [2]江苏省原子医学研究国家卫生健康委员会核医学重点实验室,江苏省分子核医学重点实验室,江苏无锡214063

出　　处：《合成化学》2023年第8期587-594,共8页Chinese Journal of Synthetic Chemistry

基　　金：国家自然科学基金资助项目(82172054);江苏省自然科学基金项目(BK20201133,BK20210062)。

摘　　要：多巴胺转运体(DAT)是许多神经退行性疾病的正电子发射断层成像(PET)靶点。目前广泛应用的DAT探针[^(18)F]FP-CIT在N-位易裂解出放射性代谢物,影响成像准确性。本研究合成了一种新型N-位烷基氘代探针[^(18)F]7,有望减缓代谢提高显像准确性。合成方法为:化合物1经过氘氢交换、还原、磺酰化和亲核取代等反应得到化合物5,化合物5与化合物6发生亲核取代得到化合物7。化合物3经磺酰化后得到化合物8,再与化合物6发生亲核取代得到化合物9,最后经磺酰化得到化合物10,所有化合物经过质谱和核磁表征。标记采用^(18)F-与10亲核取代得到探针[^(18)F]7。[^(18)F]7在磷酸盐缓冲液和胎牛血清中6 h内稳定存在,其脂水分配系数为2.2,有透过血脑屏障的潜力。简便的标记方法及良好的理化性质为[^(18)F]7的PET成像提供了坚实的基础。The dopamine transporter(DAT)in the central nervous system is the target of positron emission tomography(PET)of many neurodegenerative diseases.The DAT probe[^(18)F]FP-CIT,which is widely used at present,is easily metabolized at the N-alkyl position,and the radioactive metabolites confound the PET imaging accuracy.In this study,a novel N-alkyl deuterated probe[^(18)F]7 has been synthesized,which is expected to slow down metabolism and improve imaging accuracy.Synthetic method was as following,compound 5 was obtained from compound 1 through deuterium-hydrogen exchange,reduction,sulfonation,and nucleophilic substitution reactions.The non-radioactive compound 7 was synthesized by nucleophilic substitution of compound 5 with 6.Compound 3 was sulfonated and then nucleophilic-substitution reacted with compound 6 to yield compound 9.The labelled precursor compound 10 was obtained by sulfonation of compound 9.All compounds were characterized by mass spectrometry and NMR.The proposed deuterated^(18)F-labelled probe[^(18)F]7 was finally prepared by^(18)F-labelling procedure with^(18)F-and the precursor 10.The probe[^(18)F]7 was stable in phosphate buffer and fetal bovine serum within at least 6 h.The octanol-water partition coefficient of[^(18)F]7 was 2.2,indicating the possibility of penetrating the blood-brain barrier.The easy labelling method and good physicochemical properties laid a solid foundation for the future application of the probe[^(18)F]FP-CIT-d 6([^(18)F]7)in PET imaging.

关 键 词：正电子发射断层成像 氘代 合成 ^(18)F标记 表征 

分 类 号：R817.9[医药卫生—影像医学与核医学]