Aβ显像剂^(18)F-AV45的合成研究

Study on the synthesis of Aβ imaging agent ^(18)F-AV45

目的制备Aβ正电子显像剂^(18)F-AV45前体AV105,并利用国产氟多功能模块合成^(18)F-AV45。方法以4-氨基苯乙烯为起始原料,经Boc保护、甲基化、Heck反应、羟基保护合成AV105;AV105于130℃条件下进行亲核氟代反应,经盐酸水解、碱中和得到^(18)F-AV45,并对前体用量、盐酸浓度进行了筛选。标记前体AV105及各步合成中间体的结构均经核磁共振谱和质谱确证。结果成功合成显影剂18F-AV45,标记率为(20.3±2.2)%(n=5,未经衰减校正),HPLC检测其放化纯度(RCP)大于98%。结论初步探讨了^(18)F-AV45前体的合成与标记过程,并对反应条件进行了优化,该方法提供的显像剂可满足临床研究的要求。

Synthesis of 18 F-AV45 precursors were reported and a new automated synthesis procedure of 18F-AV45 was developed by using PET-MF-2V-IT-I synthesis module. The chemical structure of the precursor AV105 and all intermediates were verified by 1H-NMR and LC-MS. Synthesis of 18F-AV45 was performed including nucleophilic fluorination with 18 F, hydrolysis of the protecting group, neutralization and purification with semi-preparative HPLC system, is F-AV45 was obtained with a radiochemical yield of （20. 3 ± 2. 2）% （n = 5 ,no decay corrected） within a total synthesis time of about 70 min and radiochemical purity of 〉98% determined by HPLC. The present studies show that 18F-AV45 can be manufactured and used for clinic.