Nicotinic Receptor Levels After Stopping Smoking
Condition: Nicotine Addiction
MeSH terms: Tobacco Use Disorder
Study type: Observational

Summary: 
      This positron emission tomography (PET) study examines the effects of 24 hours abstinence
      from smoking on return to availability of neuronal nicotinic receptors in slow and fast
      metabolizers of nicotine.
    

Detailed description: 
      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.
    

Intervention name(s): 2-[18F]-fluro-3-[2(S)-2-azethidinylmethoxy]-pyridine
Intervention type(s): Drug
Intervention description(s): The study will be performed using an Investigational New Drug (IND) Application for the 2-[18F]FA radioligand. The 2-[18F]FA radiotracer allows us to measure nicotine receptors. The PET imaging technique used at these sessions allows us to measure the amount of light that 2-[18F]FA gives off in different regions of the brain, we can estimate how many nicotine receptors are in that region.
2-[18F]FA (radiotracer) is investigational, which means it is not approved by the United States Food and Drug Administration (FDA) for the way that it is being used in this research study. For this reason, we have received approval for all procedures in the current study including the use of 2-[18F]FA from the FDA.
Other intervention name(s): 2-[18F]FA, 2-FA
Observational model: Cohort
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        20 adult, non-treatment seeking smokers, reporting consumption of greater than/equal to 10
        cigarettes per day for at least 6 months will be the target population for the study.
        Participants will first be screened over the phone and then complete an in-person medical
        screen to ensure final eligibility. Enrolled participants will complete 2 PET scans and an
        MRI scan.

        6 smokers who have completed the study and have agreed to be re-contacted for future
        studies will be invited to participate in an additional procedure. Participants will be
        screened over the phone and complete an in-person medical screen to ensure final
        eligibility. Enrolled participants will complete 1 PET scan.
      
Biospecimen description: 
      Two saliva samples will be collected at the medical screening session. A 6ml saliva sample
      will be used for nicotine metabolite ratio (NMR) estimation, and a 2ml saliva sample for DNA
      extraction (using an Oragene collection kit).
    
Keywords: PET Scan