腺苷A_(2A)受体显像剂~(11)C-KW6002的合成与初步生物学评价

腺苷A_(2A)受体与中枢神经退行性疾病密切相关,正电子核素标记的腺苷A_(2A)受体显像剂可用于帕金森病(PD)的诊断与疗效评价。本研究采用碳-11标记(E)-1,3-二乙基-8-(3,4-二甲氧基苯乙烯)-7-甲基-3,7-双氢-1H-嘌呤-2,6-二酮](KW6002)制备~(11)C-KW6002,并进行正常鼠与PD模型鼠microPET显像。结果显示,以去甲基KW6002为标记前体,在NaOH条件下与三氟甲基磺酰基碳-11甲烷(~(11)CH_3-Trifcate)反应,标记率达56%(衰变校正,n=3)。经制备HPLC分离和固相萃取,产品放化纯度99.5%,比活度为1.5×10~(14)Bq/g。~(11)C-KW6002的microPET显像结果显示,正常大鼠双侧纹状体呈对称显像,PD模型鼠中毁损侧纹状体放射性较对侧明显增加,而同一模型的~(11)C-CFT显像为毁损侧纹状体放射性缺失。表明~(11)C-KW6002为具有临床应用的潜在腺苷A_(2A)受体显像剂。

The Synthesis and Evaluation of 11C-KW6002 as the PET Adenosine 2A Receptor Imaging Agent

PET with selective adenosine 2A receptor (A2A) radiotracers can be used to study a neurodegenerative disorders in vivo and to diagnose of PD.The PET radiotracer ne-KW6002 for imaging A2A was synthesized and evaluated,in normal and PD module rats.The results showed that the labeling yield was 56％ (decay corrected yield,n=-3) when 11CH3-Triflate reacted with nor-KW6002 under NaOH.The radiochemical purity of product was 99.50％ with specific activity of 1.5 × 1014 Bq/g.The balance of radioactivity in striatum was observed in normal rats with microPET.A significant raised radioactivity on the striatum of lesion compared with the normal side.The radioactivity was found absence on the striatum of lesion with 11C-CFT.11C-KW6002 is a potential PET radiotracer for imaging A2A.