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

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 g...

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Bibliographic Details
Published in:Journal of labelled compounds & radiopharmaceuticals 2020-07, Vol.63 (9), p.408-418
Main Authors: Lahdenpohja, Salla, Keller, Thomas, Forsback, Sarita, Viljanen, Tapio, Kokkomäki, Esa, Kivelä, Riikka V., Bergman, Jörgen, Solin, Olof, Kirjavainen, Anna K.
Format: Article
Language:English
Subjects:
Alkylation
Automation
Cannabinoid CB1 receptors
Cleanrooms
Fluorination
fluoroalkylation
GMP
Good Manufacturing Practice
High-performance liquid chromatography
nucleophilic 18F‐fluorination
positron emission tomography
Purification
Radiochemistry
radiopharmaceutical
Synthesis
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Summary: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. [18F]FMPEP‐d2 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
ISSN:0362-4803
1099-1344
DOI:10.1002/jlcr.3845