多巴胺转运蛋白显像剂^(11)C-β-CFT的全自动化合成

Full Automated Synthesis of ^(11)C-β-CFT as a Dopamine Transporter Imaging Agent

通过对反应条件的优化及合成模块的改进,探索了一种高效、全自动化合成11C-β-CFT的方法。以11CO2为起始原料与LiAlH4、HI或HBr反应生成11CH3I(或11CH3Br),再转化成Triflate-11CH3,最后与nor-β-CFT进行甲基化反应合成11C-β-CFT。整个合成工艺实现了全自动化,产品校正放化产率为70.2%±1.8%,放化纯度大于95%。用新方法合成的11C-β-CFT无菌注射液经pH测定、HPLC检测、内毒素检查、细菌培养及异常毒性检查,均符合注射液要求。用制备的11C-β-CFT对正常志愿者与帕金森病患者进行PET显像,PET显像显示正常对照者双侧纹状体影像清晰,帕金森病患者双侧纹状体不对称性摄取减低。该工艺实现了11C-β-CFT全自动化,放化产率高,工艺简单,有利于工作人员放射防护,显像效果良好,可满足临床需要。

To develop an automatic and efficient synthesis of ^11C-β-CFT as a dopamine transporter imaging agent for clinical use, ^11C-β-CFT was prepared from ^11C-Triflate-CH3 by methylation with nor-β-CFT,and then purified by a C-18 Sep-Pak. Fully automated radiosynthesis of ^11C-β-CFT was carried out. The corrected radiochemical yield of ^11C-β-CFT was 70.2%±1. 8% from nCH3I or ^11CH3Br, and the radiochemical purity was above 95%. PET imaging was performed on healthy volunteers and patients with Parkinson＇s Disease （PD）. PET imaging showed high radioactivity uptake of ^11C-β-CFT in the bilateral striatums symmetrically for the healthy volunteers, but lower radioactivity uptake in the bilateral striatums asymmetrically for the PD patients. This simple automated synthesis of ^11C-β-CFT is efficient with high yields, helpful with the radiation protection of personnel, and satisfactory to clinical applications.