靶向磷酸二酯酶5正电子核素探针的一步法合成  

One-step radio synthesis of phosphodiesterase 5 targeted Positron emission tomography tracer

作　　者：张晓锋 李鹏 赵卫威 吴小艾[2] 闫守财 杨建伟 ZHANG Xiaofeng;LI Peng;ZHAO Weiwei;WU Xiaoai;YAN Shoucai;YANG Jianwei(PET-CT Center,the Affiliated Cancer Hospital,Zhengzhou Unirersity,Henan,Zhengzhou,450008 P.R.China;Laboratory of Clinical Nuclear Medicine,West China Hospital,Sichuan University,Chengdu,Sichuan,610041 P.R.China)

机构地区：[1]郑州大学附属肿瘤医院PET-CT中心,河南郑州450008 [2]四川大学华西医院核医学科,四川成都610041

出　　处：《华西药学杂志》2020年第6期608-612,共5页West China Journal of Pharmaceutical Sciences

基　　金：四川省科技厅重点项目(编号:2017JY0324)。

摘　　要：目的研究靶向磷酸二酯酶5(PDE5)正电子核素探针制备的新方法。方法以去甲基西地那非为原料,通过亲核反应引入侧链制备18F正电子核素标记的前体与标准品,并采用经典18F亲核取代反应一步法制备靶向PDE5的核素标记探针。结果成功制备了靶向PDE5的正电子核素探针,并通过在线制备HPLC系统纯化了该探针,收率达到了35%。结论采用一步法标记该靶向PDE5的核素探针,避免了传统两步法制备探针容易出现的收率低、副反应多、时间长等缺点,简化了操作步骤,提高了收率,有助于该探针的临床应用。OBJECTIVE To investigate novel approach to the phosphodiesterase 5(PDE5)targeted Positron emission tomography(PET)radio-tracer.METHODS N-Desmethyl sildenafil was selected as starting material and was linked with side chains via SN2 reactions to prepare precursor of radio-labeled compound and reference standard.The 18F-labeled compound was also prepared via the SN2 reaction with 18F-KF.RESULTS The 18F-labeled sildenafil analogue was successfully prepared via one step SN2 reaction and purified with the online semiprep-HPLC system,with overall yield of 35%.CONCLUSION Compared with published two-step methods to prepare 18F-labeled sildenafil analogue as PDE5 PET tracer,one-step method shows superior advantages such as higher yield,time-saving,convenience in set-up,and handling the reaction conditions.And therefore it is helpful for the clinic translation of this PET tracer.

关 键 词：磷酸二酯酶 抑制剂 正电子核素探针 一步法标记 正电子发射断层显像 西地那非 衍生物 标记前体 

分 类 号：R914[医药卫生—药物化学]