PET肿瘤显像剂S-11C-甲基-L-半胱氨酸的制备与质量控制

目的 S-11C-甲基-L-半胱氨酸是一种肿瘤显像剂,是11C-MET类似物,我们自行研制合成了11C-MCYS,并对其质量控制.方法由医用回旋加速器生产11CO2,11CO2通过11CH3I全自动合成系统转化为11C-碘代甲烷(11CH3I).11CH3I与前体L-半胱氨酸的碱性溶液在Sep-Pak Plus C18小柱上发生烷基化反应,经Sep-Pak Plus C18小柱分离,得到11C-MCYS.并对新制剂进行质量控制.结果回旋加速器生产的11CO2传输到11CH3I全自动合成模块,11CO2经氢化锂铝还原转化为11CH3OH,再经氢碘酸(HI)碘代法生产出11CH3I,11CO2转化为11CH3I的时间约为8-10min,未校正放化产率约60%-70%.11C-MCYS放化合成时间约为2min,放化纯度大于98%,总合成时间约12min.主要质量控制指标达到正电子放射性药物质量要求.结论11C-MCYS的合成操作简便,产品化学纯度、放化纯度、pH值都符合注射剂的要求,符合进一步的动物探索性研究要求.

Synthesis and quality control of S-11C-methyl-L-cysteine,A New Amino Acid PET Tracer for Cancer Imaging

Objective 11C-MCYS is a tumor imaging agent, as an analogue of 11C-MET. We expore the method and quality control of 11C-MCYS. Methods 11CO2 was produced by 14N（p,α）11C nuclear reactions, which was delivered to the radiochemical laboratory. 11CO2 was trapped and released into the synthesis module. Production of 11CH3I consisted of the reduction of l11co2 with LiA1H4, hydrolysis of the intermediately formed organometallic complex and subsequent iodinatlon of llC-methanol with hydrogen iodide, 11CH3I was delivered to a Sep-Pak plus C18 cartridge previously loaded with a solution of L-cysteine（2-3mg） dissolved in NaOH 0.5mol/L in ethanol/water 50/50{v/v, 0.210ml）. 11C-MCYS was eluted with NaH2PQ 0.05mol/L buffer（5ml, pH 3-4） and collected in a vented sterile vial. Contents and analytical methods of quality control for 11C-MCYS were investigated. Results 11CH3I was prepared routinely in our laboratories by utilizing a simple remotely controlled chemical module. The uncorrected radiochemical yield of 11CH3r was 60-70% from 11CO2 and the synthesis time was 8-10min after release of 11CO2. 11C-MCYS was prepared by adopting on-column methylation described above. The uncorrected radiochemical yield of 11C-MCYS was 60%-70% with the synthesis time of 2 rain. The radiochemical purity of 11C-MCYS was above 98%, and the total synthesis time about 12 min. Conlusion It is easy to perform the automated synthesis of 11C-MCYS. All quality criteria of 11C-MCYS met the requirements of the positron radio-pharmaceuticals.