Automated GMP production and long‐term experience in radiosynthesis of CB₁ tracer [¹⁸F]FMPEP‐d₂.

Lahdenpohja, Salla; Keller, Thomas; Forsback, Sarita; Viljanen, Tapio; Kokkomäki, Esa; Kivelä, Riikka V.; Bergman, Jörgen; Solin, Olof; Kirjavainen, Anna K.

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

ALKYLATING agents; CURRENT good manufacturing practices; CANNABINOID receptors; CLEAN rooms; NUCLEOPHILIC reactions; POSITRON emission tomography

Journal of Labelled Compounds & Radiopharmaceuticals, 2020, Vol 63, Issue 9, p408

0362-4803

Academic Journal

10.1002/jlcr.3845