Abstract
607
Objectives Nicotine in tobacco elicits its addictive properties by interaction with the α4β2 nicotinic receptors. Using 18F-Nifene, a high affinity PET tracer (Ki=0.50 nM) with faster kinetics of binding, we have evaluated α4β2 receptor occupancy (OCC) by nicotine in the rat using MicroPET (MPET) imaging.
Methods 18F-Nifene was synthesized as reported (Pichika et al., 2006). Sprague Dawley rats (600 g) anesthetized with isoflurane were used for MPET studies. Test-retest was carried out after iv 18F-Nifene (0.8 to 1 mCi) to evaluate reproducibility. Rats were imaged for 90 mins and binding potential (BPND) measured. Post-18F-Nifene nicotine challenge was used to measure reversibility. For nicotine OCC, various doses (0, 0.02, 0.1, 0.25 and 0.50 mg/kg) 15 mins before 18F-Nifene were administered. Data was analyzed using ASIPRO and PMOD.
Results 18F-Nifene binding to thalamic and extra-thalamic brain regions was consistent with the α4β2 nicotinic receptors distribution in rat brain from in vitro studies. Test-retest values for the thalamus varied less than 5% (BPND =1.30, n=3 rats, using reference cerebellum (CB)), confirming reliability of 18F-Nifene binding. Post-injection of nicotine (0.3 mg/kg, +30 min) rapidly displaced specifically bound 18F-Nifene. Low dose nicotine (0.02 mg) reached 50% OCC while at higher doses (0.5 mg) >90% OCC was observed. The small amounts of 18F-Nifene binding in reference CB may affect accurate evaluation of OCC. Cortical regions exhibited similar high OCC.
Conclusions Dose-dependent effects of nicotine were observed on the binding of 18F-Nifene suggesting its potential use in the study and management of tobacco dependence.
Research Support NIH R01 AG029479
- © 2009 by Society of Nuclear Medicine