(-)-[18F]Flubatine: evaluation in rhesus monkeys and a report of the f irst fully automated radiosynthesis validated for clinical use

(-)-[F-18]Flubatine was selected for clinical imaging of (42) nicotinic acetylcholine receptors because of its high affinity and appropriate kinetic profile. A fully automated synthesis of (-)-[F-18]flubatine as a sterile isotonic solution suitable for clinical use is reported, as well as the first evaluation in nonhuman primates (rhesus macaques). (-)-[F-18]Flubatine was prepared by fluorination of the Boc-protected trimethylammonium iodide precursor with [F-18]fluoride in an automated synthesis module. Subsequent deprotection of the Boc group with 1-M HCl yielded (-)-[F-18]flubatine, which was purified by semi-preparative HPLC. (-)-[F-18]Flubatine was prepared in 25% radiochemical yield (formulated for clinical use at end of synthesis, n=3), >95% radiochemical purity, and specific activity=4647Ci/mmol (171.9GBq/mu mol). Doses met all quality control criteria confirming their suitability for clinical use. Evaluation of (-)-[F-18]flubatine in rhesus macaques was performed with a Concorde MicroPET P4 scanner (Concorde MicroSystems, Knoxville, TN). The brain was imaged for 90min, and data were reconstructed using the 3-D maximum a posteriori algorithm. Image analysis revealed higher uptake and slower washout in the thalamus than those in other areas of the brain and peak uptake at 45min. Injection of 2.5 mu g/kg of nifene at 60min initiated a slow washout of [F-18]flubatine, with about 25% clearance from the thalamus by the end of imaging at 90min. Copyright (c) 2013 John Wiley & Sons, Ltd.