^(18)F-fallypride的全自动化合成及microPET/CT显像效果评估

Automatic synthesis of ^(18)F-fallypride and evaluation of microPET/CT imaging effect

目的建立(S)-(-)-N-(1-烯丙基吡咯烷-2-氨基甲基)-5-(3-[^(18)F]丙基)-2,3-二甲氧基苯甲酰胺(^(18)F-fallypride)的全自动化合成方法,探讨其microPET/CT显像及生物分布。方法采用AIO合成模块、一次性卡套和试剂盒自动化合成^(18)F-fallypride,经组合柱(HLB+中性氧化铝柱)纯化得到终产物,测定其放化纯及产率。建立帕金森病(PD)ICR模型小鼠及SD模型大鼠,观察^(18)F-fallypride在24只PD模型小鼠体内的生物分布;另取12只SD大鼠(模型组6只、对照组6只)行microPET/CT显像,观察^(18)F-fallypride在各脑区的摄取。结果通过合成模块自动化合成的^(18)F-fallypride产率为(10±1)%(n=5,未衰减校正),总合成时间约40 min,放化纯>95%,在生理盐水和血清中室温放置120 min放化纯仍>95%。PD模型小鼠生物分布示^(18)F-fallypride主要经肾代谢,肝毒性小,脾摄取值低。MicroPET/CT显像示^(18)F-fallypride在脑部纹状体摄取明显,PD模型组SUV比值有低于对照组的趋势(5.00±0.93与6.53±1.96)。结论利用改进的多功能模块成功自动化制备^(18)F-fallypride,操作简便、合成产率稳定、质量控制结果符合使用标准,可满足后续生产质量管理规范(GMP)体系标准化生产的要求。

Objective To establish an optimized automatic synthesis method of ^(18)F-fallypride,and evaluate its biodistribution and microPET/CT characteristics.Methods ^(18)F-fallypride was automatically prepared by AIO synthesis module and disposable cassette&reagents kit.The crude product was purified by a dedicated coupled column(HLB+Alumin-N)to obtain the final product.Radiochemical purity and radiolabeling yield were determined.Parkinson′s disease(PD)model mice and rats were established.The radioactive distribution of different organs of PD model mice(n=24)were monitored.The distribution process of the agent in the SD rat brain(PD model,n=6;normal rat,n=6)were evaluated by microPET/CT imaging.Results The radiochemical yield of ^(18)F-fallypride synthesized by automatic synthesis module was stable at(10±1)%(n=5,no decay corrected).The total synthesis time was about 40 min.The radiochemical purity of ^(18)F-fallypride was more than 95%,and the radiochemical purities were also over 95%after being stored in saline and serum for 120 min at room temperature.^(18)F-fallypride was mainly excreted by the kidneys,and it was less radioactive intake in the liver and spleen in PD mice.MicroPET/CT imaging showed that higher accumulation of ^(18)F-fallypride was noted in corpus striatum and the SUV ratio of PD group was lower than that of control group(5.00±0.93 vs 6.53±1.96).Conclusion ^(18)F-fallypride can be successfully prepared automatically by improved multifunctional module,with the advantages of convenient preparation,stable radiochemical yield,satisfying purity and quality control,so it can be used in the follow-up standardized production of Good Manufacture Practice(GMP)system.