多巴胺转运蛋白显像剂^(18)F-β-FP-CIT的合成与质量控制

Synthesis and quality control of ^(18)F-β-FP-CIT as a dopamine transporter imaging agent

目的 研制多巴胺转运蛋白显像剂1 8F N 3 氟丙基 2 β 甲酯基 3 β (4 碘苯基 )降托烷(1 8F β FP CIT)。 方法 1 8F β FP CIT经两步法制备 :1,3 二溴丙烷在相转移催化剂氨基聚醚钾复合物(K K2 2 2 ) + 1 8F- 存在下发生亲核氟化反应 ,生成1 8F 氟丙基溴 ,后者与前体 2 β 甲酯基 3β (4 碘苯基 )降托烷 (nor β CIT)反应生成1 8F β FP CIT。测定1 8F β FP CIT主要质量控制指标。 结果 1 8F β FP CIT平均总放化产率约为 8% ,总放化合成时间约为 90～ 110min ,放射化学纯度大于 99% ,其他主要质量控制指标达到放射性药物质量要求。结论 合成的1 8F β FP

Objective To develop 18 F N 3 fluoropropyl 2 β carbomethoxy 3 β (4 iodophenyl)nortropane( 18 F β FP CIT)as dopamine transporter imaging agent. Methods The labelling of 18 F β FP CIT was performed via a two step synthesis. The 18 F fluoropropyl bromide was prepared through a nucleophilic substitution by the use of the aminopolyether potassium complex (K/K222) + 18 F - as a phase transfer reagent, and then by N fluoroalkylation of 2 β carbomethoxy 3 β (4 iodophenyl)nortropane (nor β CIT) with 18 F fluoropropyl bromide the 18 F β FP CIT was formed. Contents and analytical methods of quality control for 18 F β FP CIT were investigated and the main quality criteria were achieved through strict control of the determining parameters by standard procedures. Results The mean overall radiochemical yield from starting 18 F fluoride was about 8%, the total radiochemical synthesis time was about 90～110 min, and the radiochemical purity was better than 99% by HPLC and TLC. Tests on sterility and apyrogenicity of 18 F β FP CIT obtained by standard procedures were negative, and tests on other main quality criteria met the requirements of the local pharmacopoeia. Conclusion 18 F β FP CIT injection can be used in the animal and human PET study.