Radiopharmaceutical Chemistry Laboratory, Turku PET Centre, University of Turku, Turku, Finland.
Department of Chemistry, University of Turku, Turku, Finland.
J Labelled Comp Radiopharm. 2020 Jul;63(9):408-418. doi: 10.1002/jlcr.3845. Epub 2020 Jul 1.
Here, we describe the development of an in-house-built device for the fully automated multistep synthesis of the cannabinoid CB receptor imaging tracer (3R,5R)-5-(3-([ F]fluoromethoxy-d )phenyl)-3-(((R)-1-phenylethyl)amino)-1-(4-(trifluoromethyl)phenyl)pyrrolidin-2-one ([ F]FMPEP-d ), following good manufacturing practices. The device is interfaced to a HPLC and a sterile filtration unit in a clean room hot cell. The synthesis involves the nucleophilic F-fluorination of an alkylating agent and its GC purification, the subsequent F-fluoroalkylation of a precursor molecule, the semipreparative HPLC purification of the F-fluoroalkylated product, and its formulation for injection. We have optimized the duration and temperature of the F-fluoroalkylation reaction and addressed the radiochemical stability of the formulated product. During the past 5 years (2013-2018), we have performed a total of 149 syntheses for clinical use with a 90% success rate. The activity yield of the formulated product has been 1.0 ± 0.4 GBq starting from 11 ± 2 GBq and the molar activity 600 ± 300 GBq/μmol at the end of synthesis.
在这里，我们描述了一种内部构建的设备的开发，用于根据良好生产规范，全自动进行多步骤合成大麻素 CB 受体成像示踪剂（3R,5R）-5-（3-([F]氟甲氧基-d)苯基）-3-(((R)-1-苯乙基)氨基)-1-（4-（三氟甲基）苯基）吡咯烷-2-酮（[F]FMPEP-d）。该设备与 HPLC 和无菌过滤单元接口，位于洁净室热室中。合成包括亲核 F-氟化烷基化试剂及其 GC 纯化、随后前体分子的 F-氟烷基化、F-氟烷基化产物的半制备 HPLC 纯化以及其用于注射的制剂。我们已经优化了 F-氟烷基化反应的持续时间和温度，并解决了制剂产品的放射化学稳定性问题。在过去的 5 年（2013-2018 年）中，我们总共进行了 149 次用于临床使用的合成，成功率为 90%。从 11 ± 2GBq 开始，制剂产品的放射性活度产率为 1.0 ± 0.4GBq，合成结束时的摩尔活度为 600 ± 300GBq/μmol。
