探讨多巴胺转运蛋白显像剂^(11)C-β-CFT合成效率的影响因素

Optimization of the Radiosynthesis of the Dopamine Transporter Imaging Agent of ^(11)C-β-CFT

本文以^(11)C-Triflate-CH3为甲基化试剂合成多巴胺转运蛋白显像剂^(11)C-β-CFT,探讨^(11)C-β-CFT合成效率的影响因素,优化合成条件,提高其合成效率。使用国产合成模块PET-CM-3H-IT-Ⅰ全自动化合成^(11)C-β-CFT,通过研究合成过程中反应溶剂、轰靶时间、前体量及淋洗终产品条件等影响因素,得到优化后^(11)C-β-CFT的生产条件:轰靶时长10~24 min,前体浓度为0.5~1.0g/L,以0.2 mL体积比V(丙酮)∶V(乙腈)=1∶1为溶剂,反应条件为室温。从传输^(11)C-CO2到终产品的总合成时间为16min,产量为(8.07±1.94)GBq(n=76);此条件下^(11)C-β-CFT的合成效率为(76.93±6.49)%(n=76,^(11)CTriflate-CH3校正效率),产品的放化纯度大于97%,比活度(56.26±1.55)TBq/g。优化后的生产条件可以提高^(11)C-β-CFT合成效率,解决了Sep-Pak C18柱残留产品过多的问题,可实现稳定、全自动化合成^(11)C-β-CFT且保证产品满足临床需求。

The optimization for high synthesis yield was designed with ^（11）C-Triflate-CH_3I as methylation agent for dopamine transporter imaging agent of ^（11）C-β-CFT.The influence factors of the synthesis process were discussed,and the optimum synthetic conditions were established.In the paper,the study showed that the amount of precursor,the irradiation time,eluated condition,the reaction solvent etc could effect the synthetic efficiency.^（11）C-β-CFT was automatic synthesized on PET-CM-3 H-IT-Ⅰ with the optimum process conditions as the irradiation time 10-24 minutes,0.5-1.0 g/L of precursorin 0.2 mL acetone：acetonitrile（1∶1,V∶V）and room temperature.We obtained a radiochemical yield of（76.93±6.49）%（n=76,^（11）C-Triflate-CH3 EOB）.The radiochemical purity of final products were over 97%.The specific activities of final products were over（56.26±1.55）TBq/g.It took 16 minutes from^（11）C-CO2 to ^（11）C-β-CFT and the radio activity of ^（11）C-β-CFT were（8.07±1.94）GBq（n=76）.By optimization of the technological conditions,the target product was suitable for clinical,the synthetic process was reliable and full automated,the product yield was improved and the residual problem of Sep-Pak C18 was resloved.