多发性硬化症显像剂^(11)C-CIC的合成

Synthesis of ^(11)C-CIC for PET Imaging of Multiple Sclerosis

自动化合成了靶向髓磷脂(myelin)的PET显像剂4-(4-(4-氨基苯乙烯基)-2,5-二甲氧基苯乙烯基)-[N-甲基-11碳]苯胺(11 C-CIC),通过研究其在小鼠生物体及大鼠大脑中的分布,判断其作为多发性硬化(multiple sclerosis,MS)诊断或疗效评价的可行性。在多功能模块上将11 C-CH3-Triflate直接与前体反应,经HPLC分离、纯化得到11 C-CIC,采用NH小鼠用于研究11 C-CIC的生物学分布,Wistar大鼠行Micro PET/CT显像。11 C-CIC合成效率为55%~65%(n>10),放化纯度大于99%,比活度为60GBq/μmol。11 C-CIC的体外稳定性较差,加入10g/L的抗坏血酸能防止其分解。11 C-CIC初始脑摄取为2.78%ID/g,放射性主要通过肝、肾排泄。Micro PET/CT显像表明,大鼠大脑对11 C-CIC摄取较好。结果表明,制备11 C-CIC时需加入抗坏血酸以提高其体外稳定性,11 C-CIC有可能应用于髓鞘斑显像,用于诊断或评价MS的进展。

Multiple sclerosis（MS）is an inflammatory neurodegenerative disorder of central nervous system.Imaging of myelin tracts in vivo would greatly improve the diagnosis and monitoring of MS.The ^11C-CIC was synthesized with ^11C-CH3-Triflate at high yields,and was confirmed by biodistribution and imaging.^11C-CH3-Triflate was distilled and trapped into a reaction vial containing the 2mg precursor.The final production was purified by semi-HPLC to get ^11C-CIC.The in vitro stability of ^11C-CIC was studied at RT with or without Vc.The normal NH mice were sacrificed at different time after injection of ^11C-CIC for biodistribution.The micro PET/CT was performed at30 min post-injection.The radiochemical yield was 55%-65% decay corrected to ^11CH3-Triflate.The radiochemical purity was over 99% at specific activity of 60GBq/μmoL.The HPLC showed the poor stability of ^11C-CIC in vitro.The ^11C-CIC was very stable after the 10g/L Vc used as stabilizer.The initial uptake of the cerebrum was 2.78%ID/g.The radioactivity were excreted from the digestive system and urine.The micro PET/CT imaging showed good uptake in the cerebrum.The stability of ^11C-CIC can be improved with Vc as stabilizer.The ^11C-CIC was a candidate for imaging of myelin tracts for diagnosis or monitor MS.