阿片受体PET显像剂11C-卡芬太尼的制备及其生物学分布

Synthesis of opiate receptor radioligand 11C-carfentanil and its biodistribution in rats

目的建立应用国产11C-模块自动化制备阿片受体PET显像剂11C-卡芬太尼（CFN）的方法，研究其在大鼠体内的生物学分布。方法11C-碘代甲烷（CH3I）在线转化为11C-三氟甲基磺酰甲烷（Triilate—CH，），后者通入装有0．5mg前体去甲基卡芬太尼（溶解于0．15ml二甲基亚砜溶液）的V型瓶内，在常温下对前体进行甲基化反应并完成11C-标记，使用Sep—PakC2柱纯化产物。正常SD大鼠尾静脉注入11C-CFN后5，15，30，45min处死，研究其体内生物学分布，以％ID／g表示。采用SPSS13．0软件，非正态分布资料各组间均数比较采用非参数检验。结果在线自动化制备11C-CFN合成时间约20min（加速器轰击结束，EOB），平均产率为（35．5±2．2）％（n=12，不校正），无需经HPLC纯化，放化纯〉98％。11C-CFN在大鼠体内吸收、分布迅速，主要通过肝、肾代谢，脑内放射性摄取高，注射后5min达峰值，以丘脑[（4．26±0．89）％ID／g]和纹状体[（4．05±1．08）％ID／g]的分布最为显著，其次分别为大脑皮质[（2．63±0．89）％ID／g]、脑干[（2．26±0．57）％ID／g]、海马[（2．17±0．55）％ID／g]和小脑[（2．15±0．39）％ID／g]。结论使用国产11C-模块自动化制备11C-CFN简便快速、产率稳定、放化纯高，可用于阿片受体PET显像研究。

Objective To establish an automatic synthesis method for HC-carfentanil （CFN） as an novel opiate receptor radioligand and study its biodistribution in rats. Methods 11C-Triflate-CH3 was bubbled into 0.5 mg precursor desmethyl-CFN （which was dissolved in 0.15 ml DMSO） to generate 11C-CFN in a V-tube at room temperature. Sep-Pak C2 column was used for purification of 11C-CFN, which was eluted by 3ml binary system aqueous solution, 10 ml water thrice, and then 1 ml ethanol. The biodistribution （ % ID/g） of 11C-CFN in SD rats was studied. SPSS 13.0 was used for statistical analysis. Non-normal distribution data were analyzed using nonparametric test. Results The synthesis time for 11 C-CFN was 20 min （end of bombardment, EOB）. The synthesis yield was （35.5 ± 2.2） % on average （n = 12, uncorrected） with the radioehemieal purity over 98%. Biodistribution study in rats showed that the tracer had a high brain uptake, rapid blood clearance, and a metabolic pathway via liver and kidney. The highest tracer uptake was in thalamus （ 4.26 ± 0.89 ） % ID/g and striatum （4.05 ±1.08 ） % ID/g at 5 min after injection, followed by cerebral cortex （2.63 ＋ 0.89） % ID/g, pons （2.26 ± 0. 57 ） % ID/g, hippocampus （2. 17 ± 0.55 ） % ID/g and cerebellum （2. 15 ±0.39） %ID/g. Conclusions The automatic synthesis of nC-CFN is fast and reliable, and this radioligand can be used for opiate receptor imaging.