Nicotinic Receptor Availability in Slow and Fast Nicotine Metabolizers
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.
Observational
Observational Model: Cohort, Time Perspective: Prospective
Change in α4β2* nAChR binding potential
This study uses a mixed design. A within-subject positron emission tomography (PET) study comparing α4β2* nAChR availability, using 2-[18F]FA PET imaging, at two timepoints (1) during smoking as usual; and (2) after 24 hours of overnight abstinence. The order of the PET scans will be counterbalanced across subjects to prevent order effects that could bias the study results. Nicotine metabolite ratio (NMR) serves as the between-subject factor. The minimum amount of time between scans will be separated by one week. The maximum amount of time allowable between scans will be 4 weeks.
Week 1 and up to Week 5
No
Caryn Lerman, PhD
Principal Investigator
University of Pennsylvania
United States: Food and Drug Administration
812051
NCT01704573
October 2010
December 2012
Name | Location |
---|---|
Center for Interdisciplinary Research on Nicotine Addiction, University of Pennsylvania | Philadelphia, Pennsylvania 19104 |