title: Automated one-step radiosynthesis of the CB1 receptor imaging agent [(18) F]MK-9470.
abstract: The fluorine-18-labeled positron emission tomography (PET) radiotracer [(18) F]MK-9470 is a selective, high affinity inverse agonist that has been used to image the cannabinoid receptor type 1 in human brain in healthy and disease states. This report describes a simplified, one-step [(18) F]radiofluorination approach using a GE TRACERlab FXFN module for the routine production of this tracer. The one-step synthesis, by [(18) F]fluoride displacement of a primary tosylate precursor, gives a six-fold increase in yield over the previous two-step method employing O-alkylation of a phenol precursor with 1,2-[(18) F]fluorobromoethane. The average radiochemical yield of [(18) F]MK-9470 using the one-step method was 30.3 ± 11.7% (n = 12), with specific activity in excess of 6 Ci/µmol and radiochemical purity of 97.2 ± 1.5% (n = 12), in less than 60 min. This simplified, high yielding, automated process was validated for routine GMP production of [(18) F]MK-9470 for clinical studies.
authors.affiliation: Institute for Neurodegenerative Disorders, New Haven, CT, USA.
authors.forename: David
authors.initials: D
authors.lastname: Thomae
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Morley
authors.forename: Terence
authors.initials: T
authors.lastname: Hamill
authors.forename: Vincent M
authors.initials: VM
authors.lastname: Carroll
authors.forename: Caroline
authors.initials: C
authors.lastname: Papin
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Twardy
authors.forename: H Sharon
authors.initials: HS
authors.lastname: Lee
authors.forename: Richard
authors.initials: R
authors.lastname: Hargreaves
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Baldwin
authors.forename: Gilles
authors.initials: G
authors.lastname: Tamagnan
authors.forename: David
authors.initials: D
authors.lastname: Alagille
mesh_terms: D011725:Pyridines / Q000138:chemical synthesis*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis*
chemical_list: C528731:MK-9470; D011725:Pyridines; D019275:Radiopharmaceuticals
keywords: CB1; Good Manufacturing Practice (GMP); Production; [18F]MK-9470