β淀粉样蛋白PET显像剂^(11)C-DPOD的制备及其在动物体内的分布

Synthesis and Biological Evaluation of ^(11)C-DPOD for PET Imaging Agent of Amyloid-b in Mouse Brain

目的研究脑内β淀粉样蛋白(Aβ)的PET显像剂11C-DPOD即[N-甲基-11C]-3,5-二苯基-1,2,4-苯并噻唑的制备路线和在动物体内的分布情况。方法使用11C-三氟甲基磺酰甲烷(11C-triflate-CH3)和2 mg自制DPOD前体(溶于0.1 mL丁酮中,摇匀后装于3 mL的特制密闭反应瓶中,置-20℃)反应,在80℃水浴中对前体进行甲基化反应并完成11C标记。反应后的液体加入5 mL注射用水稀释,过活化的固相C18柱除去杂质,再用乙醇0.5 mL洗脱保留在柱上的产品。经无菌注射水稀释和0.22μm的微孔无菌滤膜过滤,得到澄清11C-DPOD乙醇水溶液。经尾静脉注射于转基因型阿尔茨海默病(AD)小鼠(AD小鼠)、正常C57老龄小鼠(正常老龄小鼠,作为对照);经肘静脉注射猕猴,进行动态显像。结果11C-DPOD注射液为无色澄清透明液体(pH 7.0),含10%的乙醇,放射性化学纯度>98%,产率为10%~15%。在AD小鼠和正常老龄小鼠体内显像差异无统计学意义;在猕猴体内11C-DPOD主要通过肝脏和胆囊代谢。结论11C-DPOD为合成的可以快速在转基因型痴呆小鼠和猕猴脑分布及清除的新型AβPET显像剂。

Aim To study the synthesis of ^11C-labeled PET amyloid-β （Aβ） imaging agent titled DPOD, a new series of ^11C-6-OH-BTA-1 derivatives, and biological evaluation of ^11C-DPOD for detecting amyloid-β plaques in mouse brain. Methods ^11C-triflate-CH3 was bubbled into 2 mg precursor DPOD, which was dissolved in 0.1 mg methyl ethyl ketone, to generate HC-DPOD in a V-tube at high temperature （about 80 ℃）. The radiolabelled products were purified by HPLC. Then the image of radioactive concentration of transgenic,senile mice and rhesus monkey was made by using PET/CT. All data were analyzed by Stata 10.0 software （P〈0.05）. Results ^11C-DPOD was a kind of colorless transparent liquid with ethyl alcohol about 10%, pH7.0. The radiochemical purity was over 95% and the average radiolabeling yield was from 10% to 15%.^11C-DPOD had the same effect as ^11C-PIB in pharmacokinetics of transgenic and senile mice. Conclusion ^11C-DPOD radioactivity of brain was synthesized by ourselves and washed out quickly thereafter in both transgenic mice and monkey.