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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。
OBJECTIVE To prepare A18 positron-imaging agent (18) F-AV45 precursor AV105 and to synthesize ~ (18) F-AV45 using domestic fluorinated multifunctional modules. Methods AV105 was synthesized from 4-aminostyrene by Boc protection, methylation, Heck reaction and hydroxyl protection. AV105 was subjected to nucleophilic fluorination reaction at 130 ℃. After hydrolysis with hydrochloric acid, (18) F-AV45, and the amount of precursor, hydrochloric acid concentration were screened. The structure of the tagged precursor AV105 and the synthetic intermediates in each step was confirmed by NMR and MS. Results The 18F-AV45 reagent was successfully synthesized. The labeling efficiency was (20.3 ± 2.2)% (n = 5 without attenuation correction) and the radiochemical purity (RCP) was more than 98% by HPLC. Conclusion The synthesis and labeling of ~ (18) F-AV45 precursors were preliminarily discussed, and the reaction conditions were optimized. The imaging agents provided by this method could meet the requirements of clinical research.