Nicotinic Receptor Levels After Stopping Smoking

The nicotine metabolite ratio (NMR), a stable marker of nicotine clearance rate, is a robust predictor of smoking relapse. Individuals who are fast nicotine metabolizers have higher rates of relapse, compared to slow metabolizers, on nicotine replacement or placebo treatment. Nicotine exerts its reinforcing properties, in part, by binding to α4β2\* nicotinic acetylcholine receptors (nAChRs) in the brain. The α4β2\* nAChRs are abundant and have high affinity for nicotine relative to other nAChR subtypes. The goal of this project is to identify abstinence-induced changes in neuronal nicotinic receptor availability that may underlie risk for smoking relapse. The investigators propose to utilize positron emission tomography (PET) imaging to examine the association of variation in nicotine metabolism with return to availability of α4β2\* nAChRs during early abstinence. The investigators will measure α4β2\* receptor availability using the PET radio-ligand 2-\[18F\]FA, administered with bolus injection, on two separate occasions: during smoking as usual and after 24 hours of abstinence. The proposed study will help us understand the neurochemical mechanisms that underlie the higher risk of relapse among faster nicotine metabolizers, thereby pointing to potential targets for tailored therapy for these smokers at increased risk. In addition, the investigators will invite six subjects who have completed the two PET scans described above to complete a third PET scan. During this third PET scan, the investigators plan to measure α4β2\* receptor availability using the PET radio-ligand 2-\[18F\]FA, administered as bolus plus constant infusion after 24 hours of abstinence. The purpose will be to compare α4β2\* nAChR binding potential data from the bolus 2-\[18F\]FA infusion protocol used in the main study to the bolus plus constant infusion protocol used in this third PET scan. The protocol of this third PET scan will help the investigators demonstrate the feasibility at the University of Pennsylvania of administering the radiotracer as a bolus plus constant infusion, and the feasibility of scanning for two hours (versus one hour in the current protocol) paradigm. This data is important pilot data for future NIH grant submissions using this radiotracer.