心脏神经受体显像剂^(11)C标记羟基麻黄素合成方法优化

Synthesis Method Optimization of Cardiac Nerve Receptor Imaging Agent ^(11)C-mHED

目的:建立简便实用的正电子放射性示踪药物^(11)C标记的羟基麻黄素(^(11)C-mHED)自动化生产的方法,满足临床诊断需要。方法:首先使用加速器通过^(14)N(p,α)^(11)C核反应来生产^(11)C-CO_2,然后使用TRACERlab FXc合成模块将^(11)C-CO_2还原为^(11)C-CH_4,进一步反应生成^(11)C-CH_3I,以此作为甲基化试剂,与间羟胺前体反应得到^(11)C-mHED的混合液,经HPLC进行纯化并用0.9%氯化钠溶液稀释,通过0.22μm的微孔无菌滤膜过滤得到所需的注射液。结果:合成时间从加速器轰击结束开始共33 min,放化产率经过衰减校正后为12%±1%(n=5),化学纯度大于97%,放射化学纯度大于99%。产品的无菌及无热原要求均符合规定。结论:通过对比不同文献的方法和修改多个反应参数,简化了生产流程,节省了合成时间,实现了^(11)C-mHED注射液的计算机远程控制全自动生产,保证了生产的可行性和重现性,可完全满足临床需要。

Objective： To establish a simple and practical automatic synthesis method for positron radioactive tracer 11C-mHED to satisfy the needs of clinical diagnosis. Methods ： Firstly, 11 C-CO2 was produced through 14 N （p,α） 11C nuclear reaction by a cyclotron. Then 11 C-CO2 was reduced to 11 C-CH4 by the TRACERlab FXc synthesis module. 11 C-CH3I, the methylation reagent, was obtained by the next reaction. The mixture from the reaction of 11 C-CH3I and metaraminol was purified and separated by HPLC. Finally, the pro- duction was diluted with 0.9% saline and collected in a sterile vial. Results ： The synthesis time was 33 minutes from the end of the bombardment （EOB）. The radiochemical yield after the decay correction was 12% ± 1% （ n = 5 ）. The chemical purity of the produc- tion was above 97% , and the radiochemical purity was up to 99%. The product solution was proved to be sterile and pyrogen-free. 11 Conclusion： The production flow and time was simplified and reduced by comparing different literatures and modifying parameters. C-mHED can be easily synthesized in an automatic way by computer control, and the reliability and reproducibility of the synthesis process are good. The production can satisfy the needs of clinical routine application.