Evaluation of (18)F-nifene binding to α4β2 nicotinic receptors in the rat brain using microPET imaging

MicroPET imaging studies using (18)F-nifene, a new positron emission tomography (PET) radiotracer for nicotinic acetylcholinergic receptors (nAChR) α4β2 receptors in rats, have been carried out. Rats were imaged for 90 min after intravenous injection of (18)F-nifene (0.8 to 1 mCi), and binding potential (BP(ND)) was measured. (18)F-Nifene binding to thalamic and extrathalamic brain regions was consistent with the α4β2 nAChR distribution in the rat brain. Using the cerebellum as a reference, the values for the thalamus varied less than 5% (BP(ND )= 1.30, n = 3), confirming reproducibility of (18)F-nifene binding. (18)F-Nifene microPET imaging was also used to evaluate effects of nicotine in a group of Sprague-Dawley rats under isoflurane anesthesia. Nicotine challenge postadministration of (18)F-nifene demonstrated reversibility of (18)F-nifene binding in vivo. For α4β2 nAChR receptor occupancy (nAChR(OCC)), various doses of nicotine (0, 0.02, 0.1, 0.25, and 0.50 mg/kg nicotine free base) 15 min prior to (18)F-nifene were administered. Low-dose nicotine (0.02 mg) reached > 80% nAChR(OCC )while at higher doses (0.25 mg) > 90% nAChR(OCC )was measured. The small amount of (18)F-nifene binding with reference to the cerebellum affects an accurate evaluation of nAChR(OCC). Efforts are underway to identify alternate reference regions for (18)F-nifene microPET studies in rodents.