一锅法自动化合成3’-脱氧-3’-^(18)F-氟代胸苷和O-(2-^(18)F-氟代乙基)-L-酪氨酸  

Automated synthesis of 3’-deoxy-3’-[^(18)F]fluorothymidine and O-(2-^(18)F-fluoroethyl)-L-tyrosine as tumor imaging agents

作　　者：唐刚华[1,2] 唐小兰[3] 王明芳[1] 李葆元[1] 梁明泉[1] 

机构地区：[1]南方医科大学南方医院核医学科PET中心,广州510515 [2]中山大学附属第一医院核医学科PET-CT中心,广州510080 [3]华南农业大学理学院,广州510642

出　　处：《核技术》2009年第2期154-160,共7页Nuclear Techniques

基　　金：广东省科技计划资助项目(2003C34304);中山大学“百人计划”引进人才科研启动基金(80000-3171313);国家高技术研究发展计划(863计划)专题课题(2008AA02Z430)

摘　　要：采用"一锅法"和TRACERlab FXF-N自动化合成装置,以3-N-t-叔丁氧羰基-1-[5’-O-(4,4’-二甲氧基三苯甲基)-2’-脱氧-3’-O-(4-硝基苯磺酰基)-β-D-苏型阿呋喃糖基]胸腺嘧啶为前体,在同一反应瓶中经亲核氟化、盐酸水解两步反应及HPLC分离纯化制备18F-FLT注射液。以乙二醇二对甲苯磺酸酯为起始原料,在同一反应瓶中经亲核氟化和烷基化两步反应及HPLC分离纯化得18F-FET注射液。18F-FLT和18F-FET总合成时间分别约为60min和50min,未校正的放化产率均大于20%,放化纯度均大于95%。18F-FLT和18F-FET注射液质量控制指标符合放射性药物质量要求。For early diagnosis for malignant tumors with the different metabolic imaging agents, a fully automated synthetic technology of 3＇-deoxy-3＇-[^18F]fluorothymidine （^18F-FLT） and O-（2-^18F-fluoroethyl）-L-tyrosine （^18F-FET） was studied in this paper. Automated synthesis of ^18F-FLT and ^18F-FET was performed by one-pot two-step reaction procedure at TRACERlab FXF.N system, ^18F-FLT injection was obtained via two-step reaction including nucleophilic fluorination of 3-N-t-butoxycarbonyl- 1-[5 ＇-O-（4,4＇-di-methoxytfiphenylmethyl）-2＇-deoxy-3＇-O-（4-nitrobenzenesulfonyl）- β-D-threopentofuranosyl]thymine, the precursor molecule, with ^18F-fluoride and subsequent hydrolysis of the protecting group with 1 mol/L HCl at the same reaction vessel, and purification with HPLC system. ^18F-FET injection was also prepared via two-step reaction including nucleophilic fluorination of 1,2-di（4-methylphenylsulfonyloxy）ethane as the starting material and following by alkylation of L-tyrosine at the same reaction vessel, and purification with HPLC system. Fully automated synthesis of ^18F-FLT and ^18F-FET was completed within the total synthesis time of about 50 and 60 min, respectively. The uncorrected radiochemical yields of ^18F-FLT and ^18F-FET were above 20% and radiochemical purities were more than 95%. The quality control indexes of ^18F-FLT and ^18F-FET injection meet the requirements of radiopharmaceuticals quality.

关 键 词：18F-FLT 18F-FET 肿瘤显像剂 自动化合成 质量控制 

分 类 号：R817.4[医药卫生—影像医学与核医学]