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.

Keywords: CB1; Good Manufacturing Practice (GMP); Production; [18F]MK-9470.