Automated GMP production and long‐term experience in radiosynthesis of CB1 tracer [18F]FMPEP‐d2. (1st July 2020)

• Record Type: Journal Article
• Authors: Lahdenpohja, Salla; Keller, Thomas; Forsback, Sarita; Viljanen, Tapio; Kokkomäki, Esa; Kivelä, Riikka V.; Bergman, Jörgen; Solin, Olof; Kirjavainen, Anna K.
• Is Part Of: Journal of labelled compounds & radiopharmaceuticals. Volume 63:Number 9(2020)
• Page Start: 408
• Page End: 418
• Publication Date: 2020-07-01
• Subjects: fluoroalkylation -- GMP -- nucleophilic 18F‐fluorination -- positron emission tomography -- radiochemistry -- radiopharmaceutical; Tracers (Chemistry) -- Periodicals; Radiopharmaceuticals -- Periodicals; 615.8424
• DOI: 10.1002/jlcr.3845
• Languages: English
• ISSNs: 0362-4803

Abstract

Abstract : Here, we describe the development of an in‐house‐built device for the fully automated multistep synthesis of the cannabinoid CB1 receptor imaging tracer (3 R, 5 R )‐5‐(3‐([ 18 F]fluoromethoxy‐ d 2 )phenyl)‐3‐((( R )‐1‐phenylethyl)amino)‐1‐(4‐(trifluoromethyl)phenyl)pyrrolidin‐2‐one ([ 18 F]FMPEP‐ d 2 ), 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. Abstract : [ 18 F]FMPEP‐ d 2 production at Turku PET Centre during 2013–2018: 149 syntheses for clinical use 90% success rate 16 ± 6% RCY 1.0 ± 0.4 GBq activity yield 600 ± 300 GBq/μmol