Premium
Automated GMP production and long‐term experience in radiosynthesis of CB 1 tracer [ 18 F]FMPEP‐ d 2
Author(s) -
Lahdenpohja Salla,
Keller Thomas,
Forsback Sarita,
Viljanen Tapio,
Kokkomäki Esa,
Kivelä Riikka V.,
Bergman Jörgen,
Solin Olof,
Kirjavainen Anna K.
Publication year - 2020
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.3845
Subject(s) - radiosynthesis , chemistry , tracer , radiochemistry , term (time) , nuclear physics , positron emission tomography , nuclear medicine , physics , medicine , quantum mechanics
Here, we describe the development of an in‐house‐built device for the fully automated multistep synthesis of the cannabinoid CB 1 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.