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(−)-[18F]Flubatine was selected for clinical imaging of α4 β2 nicotinic acetylcholine receptors because of its high affinity and appropriate kinetic profile. A fully automated synthesis of (−)-[18F]flubatine as a sterile isotonic solution suitable for clinical use is reported, as well as the first evaluation in nonhuman primates (rhesus macaques). (−)-[18F]Flubatine was prepared by fluorination of the Boc-protected trimethylammonium iodide precursor with [18F]fluoride in an automated synthesis module. Subsequent deprotection of the Boc group with 1-M HCl yielded (−)-[18F]flubatine, which was purified by semi-preparative HPLC. (−)-[18F]Flubatine was prepared in 25% radiochemical yield (formulated for clinical use at end of synthesis, n = 3), >95% radiochemical purity, and specific activity = 4647 Ci/mmol (171.9 GBq/µmol). Doses met all quality control criteria confirming their suitability for clinical use. Evaluation of (−)-[18F]flubatine in rhesus macaques was performed with a Concorde MicroPET P4 scanner (Concorde MicroSystems, Knoxville, TN). The brain was imaged for 90 min, 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 45 min. Injection of 2.5 µg/kg of nifene at 60 min initiated a slow washout of [18F]flubatine, with about 25% clearance from the thalamus by the end of imaging at 90 min. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]