Automated GMP production and long-term experience in radiosynthesis of CB1 tracer [18 F]FMPEP-d 2,Journal of Labelled Compounds and Radiopharmaceuticals

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Automated GMP production and long-term experience in radiosynthesis of CB1 tracer [18 F]FMPEP-d 2
Journal of Labelled Compounds and Radiopharmaceuticals ( IF 0.9 ) Pub Date : 2020-07-01 , DOI: 10.1002/jlcr.3845
Salla Lahdenpohja ₁ , Thomas Keller ₁ , Sarita Forsback _{1,

2} , Tapio Viljanen ₁ , Esa Kokkomäki ₁ , Riikka V Kivelä ₃ , Jörgen Bergman ₁ , Olof Solin _{1,

2,

4} , Anna K Kirjavainen ₁

Affiliation

Here we describe the development of an in-house-built device for the fully automated multi-step synthesis of the cannabinoid CB1 receptor imaging tracer (3R,5R)-5-(3-([18 F]fluoromethoxy-d2 )phenyl)-3-(((R)-1-phenylethyl)amino)-1-(4-(trifluoromethyl)phenyl)pyrrolidin-2-one ([18 F]FMPEP-d2 ), 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 18 F-fluorination of an alkylating agent and its GC purification, the subsequent 18 F-fluoroalkylation of a precursor molecule, the semipreparative HPLC purification of the 18 F-fluoroalkylated product and its formulation for injection. We have optimized the duration and temperature of the 18 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.

中文翻译：

自动化 GMP 生产和 CB1 示踪剂 [18 F]FMPEP-d 2 放射合成的长期经验

在这里，我们描述了用于全自动多步合成大麻素 CB1 受体成像示踪剂 (3R,5R)-5-(3-([18 F]氟甲氧基-d2 )苯基) 的内部构建设备的开发-3-(((R)-1-苯乙基)氨基)-1-(4-(三氟甲基)苯基)吡咯烷-2-酮([18 F]FMPEP-d2)，遵循良好生产规范。该设备与洁净室热室中的 HPLC 和无菌过滤装置连接。合成过程包括烷基化剂的亲核 18 F-氟化及其 GC 纯化、随后前体分子的 18 F-氟烷基化、18 F-氟烷基化产物及其注射制剂的半制备型 HPLC 纯化。我们优化了 18 F-氟烷基化反应的持续时间和温度，并解决了配方产品的放射化学稳定性问题。在过去的5年（2013年至2018年）中，我们总共进行了149次临床合成，成功率高达90%。配制产品的活性产量从 11 ± 2 GBq 开始为 1.0 ± 0.4 GBq，合成结束时摩尔活性为 600 ± 300 GBq/μmol。

更新日期：2020-07-01

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