1. Automated one-step radiosynthesis of the CB1receptor imaging agent [18F]MK-9470
- Author
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Richard Hargreaves, Ronald M. Baldwin, Terence G. Hamill, Thomas J. Morley, Nicole M. Twardy, David Thomae, David Alagille, Gilles Tamagnan, Vincent M. Carroll, H. Sharon Lee, and Caroline Papin
- Subjects
Cannabinoid receptor ,medicine.diagnostic_test ,Chemistry ,Organic Chemistry ,Radiosynthesis ,Radiochemistry ,Analytical chemistry ,One-Step ,Biochemistry ,Imaging agent ,Analytical Chemistry ,Positron emission tomography ,Yield (chemistry) ,Drug Discovery ,medicine ,Inverse agonist ,Radiology, Nuclear Medicine and imaging ,Specific activity ,Spectroscopy - 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.
- Published
- 2014