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 monkeys.
The novel 11C-labeled nicotinic agonist (R,S)-1-[11C]methyl-2(3-pyridyl)azetidine ([11C]MPA) was evaluated as a positron emission tomography (PET) ligand for in vivo characterization of nicotinic acetylcholine receptors in the brain of Rhesus monkeys in comparison with the nicotinic ligands (S)-3-methyl-5-(1-[11C]methyl-2-pyrrolidinyl)isoxazol ([11C]ABT-418) and (S)(-)[11C]nicotine. The nicotinic receptor agonist [11C]MPA demonstrated rapid uptake into the brain to a similar extent as (S)(-) [11C]nicotine and [11C]ABT-418. When unlabeled (S)(-)nicotine (0.02 mg/kg) was administered 5 min before the radioactive tracers, the uptake of [11C]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)(-)[11C]nicotine and [11C]ABT-418. This finding indicates specific binding of [11C]MPA to nicotinic receptors in the brain in a simple classical displacement study. [11C]MPA seems to be a more promising radiotracer than (S)(-)[11C]nicotine or [11C]ABT-418 for PET studies to characterize nicotinic receptors in the brain.
Sihver
W
W
Subfemtomole Biorecognition Project, Japan Science and Technology Corporation, Osaka. Wiebke.Sihver@pet.uu.se
Fasth
K J
KJ
Ogren
M
M
Lundqvist
H
H
Bergström
M
M
Watanabe
Y
Y
Långström
B
B
Nordberg
A
A
D000818:Animals; D001384:Azetidines / Q000493:pharmacokinetics; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D002531:Cerebellum / Q000000981:diagnostic imaging / Q000378:metabolism; D007555:Isoxazoles / Q000493:pharmacokinetics; D008253:Macaca mulatta; D009538:Nicotine / Q000493:pharmacokinetics; D009928:Organ Specificity; D011759:Pyrrolidines / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D013702:Temporal Lobe / Q000000981:diagnostic imaging / Q000378:metabolism; D013788:Thalamus / Q000000981:diagnostic imaging / Q000378:metabolism; D014055:Tomography, Emission-Computed
D001384:Azetidines; D002250:Carbon Radioisotopes; D007555:Isoxazoles; D011759:Pyrrolidines; D019275:Radiopharmaceuticals; C053182:1-methyl-2-(3-pyridyl)azetidine; C088383:3-methyl-5-(1-methyl-2-pyrrolidinyl)isoxazole; D009538:Nicotine