title: Automated production at the curie level of no-carrier-added 6-[(18)F]fluoro-L-dopa and 2-[(18)F]fluoro-L-tyrosine on a FASTlab synthesizer.
abstract: An efficient, fully automated, enantioselective multi-step synthesis of no-carrier-added (nca) 6-[(18)F]fluoro-L-dopa ([(18)F]FDOPA) and 2-[(18)F]fluoro-L-tyrosine ([(18)F]FTYR) on a GE FASTlab synthesizer in conjunction with an additional high- performance liquid chromatography (HPLC) purification has been developed. A PTC (phase-transfer catalyst) strategy was used to synthesize these two important radiopharmaceuticals. According to recent chemistry improvements, automation of the whole process was implemented in a commercially available GE FASTlab module, with slight hardware modification using single use cassettes and stand-alone HPLC. [(18)F]FDOPA and [(18)F]FTYR were produced in 36.3 ± 3.0% (n = 8) and 50.5 ± 2.7% (n = 10) FASTlab radiochemical yield (decay corrected). The automated radiosynthesis on the FASTlab module requires about 52 min. Total synthesis time including HPLC purification and formulation was about 62 min. Enantiomeric excesses for these two aromatic amino acids were always >95%, and the specific activity of was >740 GBq/µmol. This automated synthesis provides high amount of [(18)F]FDOPA and [(18)F]FTYR (>37 GBq end of synthesis (EOS)). The process, fully adaptable for reliable production across multiple PET sites, could be readily implemented into a clinical good manufacturing process (GMP) environment.
authors.affiliation: Cyclotron Research Center, Université de Liège, Liège, Belgium.
authors.forename: C
authors.initials: C
authors.lastname: Lemaire
authors.affiliation: Cyclotron Research Center, Université de Liège, Liège, Belgium.
authors.forename: L
authors.initials: L
authors.lastname: Libert
authors.affiliation: GE Healthcare MDx Chemistry Systems, Ans, Belgium.
authors.forename: X
authors.initials: X
authors.lastname: Franci
authors.affiliation: Cyclotron Research Center, Université de Liège, Liège, Belgium.
authors.forename: J-L
authors.initials: JL
authors.lastname: Genon
authors.affiliation: GE Healthcare MDx Chemistry Systems, Ans, Belgium.
authors.forename: S
authors.initials: S
authors.lastname: Kuci
authors.affiliation: Cyclotron Research Center, Université de Liège, Liège, Belgium.
authors.forename: F
authors.initials: F
authors.lastname: Giacomelli
authors.affiliation: Cyclotron Research Center, Université de Liège, Liège, Belgium.
authors.forename: A
authors.initials: A
authors.lastname: Luxen
mesh_terms: D057205:Automation, Laboratory; D060326:Chemistry Techniques, Synthetic / Q000295:instrumentation / Q000379:methods; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D019275:Radiopharmaceuticals / Q000138:chemical synthesis*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis
chemical_list: D019275:Radiopharmaceuticals; C545932:(18F)fluoroethyltyrosine; C043437:fluorodopa F 18; D014443:Tyrosine; D004295:Dihydroxyphenylalanine
keywords: 2-[18F]fluoro- l-tyrosine; F-18, [18F]FDOPA; GMP; automation; solid-phase extraction