In vivo positron emission tomography studies on the novel nicotinic receptor agonist [11C]MPA compared with [11C]ABT-418 and (S)(-)[11C]nicotine in rhesus monkey

The novel C-11-labeled nicotinic agonist (R,S)-1-[C-11]methyl-2(3-pyridyl)azetidine ([C-11]MPA) was evaluated as a positron emission tomography (PET) ligand for in vivo characterization of nicotinic acetylchorine receptors in the brain of Rhesus monkeys in comparison with the nicotinic ligands (S)-3-methyl-5-(1-[C-11]methyl 2-pyrrolidinyl)isoxazol ([C-11]ABT-418) and (S)(-)[C-11]nicotine. The nicotinic receptor agonist [C-11]MPA demonstrated rapid uptake into the brain to a similar extent as (S)(-) [C-11]nicotine and [C-11]ABT-418. When unlabeled (S)(-)nicotine (0.02 mg/kg) was administered 5 min before the radioactive tracers, the uptake of [C-11]MPA was decreased by 25% in the thalamus, 19% in the temporal cortex, and 11% in the cerebellum, whereas an increase was found for the uptake of (S)(-)[C-11]nicotine and [C-11]ABT-418. This finding indicates specific binding of [C-11]MPA to nicotinic receptors in the brain in a simple classical displacement study. [C-11]MPA seems to be a more promising radiotracer than (S)(-)[C-11]nicotine or [C-11]ABT-418 for PET studies to characterize nicotinic receptors in the brain. NUCL MED BIOL 26;6:633-640 1999. (C) 1999 Elsevier Science Inc. All rights reserved.