Test-retest Reproducibility of [11C]PHNO PET Using the Constant Infusion Paradigm
Condition: Nicotine Dependence; Healthy
MeSH terms: Tobacco Use Disorder
Study type: Interventional

Summary: 
      A research study designed to examine amphetamine-induced dopamine release using the PET
      imaging agent [11C]PHNO in tobacco smokers while currently smoking and during acute
      withdrawal and in nonsmokers. Twenty healthy men and women tobacco smokers and twenty healthy
      nonsmokers will be recruited. Each subject will participate in 1 MRI and up to 2 [11C]PHNO
      PET scans. On the study day subjects will participate in two [11C]PHNO scans (ideally, the
      two PET scans will be carried out in the same day). Three hours before the second PET scan,
      amphetamine (0.5 mg/kg, PO) will be administered. In smokers, the scan will occur at 10-21
      days of smoking abstinence.
    

Detailed description: 
      To determine amphetamine-induced DA release in tobacco smokers while currently smoking and
      during acute withdrawal and in nonsmokers. Twenty healthy men and women tobacco smokers and
      twenty healthy nonsmokers will be recruited. Each subject will participate in 1 MRI and up to
      2 [11C]PHNO PET scans. On the PET study day subjects will participate in two [11C]PHNO scans
      (ideally, the two PET scans will be carried out in the same day). Three hours before the
      second PET scan, amphetamine (0.5 mg/kg, PO) will be administered. In smokers, the set of
      scans will occur at 10-21 days of smoking abstinence. Smoking abstinence will be determined
      by carbon monoxide and urine cotinine (a breakdown product of nicotine in cigarette smoke)
      levels. Subjects will be asked to breathe into a breathalyzer to measure carbon monoxide and
      to provide a urine sample to measure cotinine. Smoking abstinence will be confirmed by carbon
      monoxide and cotinine levels that are reduced as compared to actively smoking. We hypothesize
      that smokers at 10-21 days of withdrawal will have amphetamine-induced DA release that is
      blunted compared to healthy nonsmokers.

      Magnetic resonance imaging (MRI) scans (3 T) will be collected in each subject to co-register
      PET and MRI for image analysis. Within two weeks of the PET study, an MRI will be acquired at
      the Yale University MRI Center. Subjects will be taken through a ferromagnetic metal detector
      before entering the scan room. The acquisition sequence is a 3D fast spoiled grass (FSPGR) MR
      pulse sequence with an IR prep of 300 ms. (TE= 3.3 ms, flip angle=17 degrees; slice
      thickness= 1.2 mm) optimized for delineating gray matter/white matter/CSF boundaries. The
      small voxel size (0.93 X 1.2 X 0.93 mm) provides high-resolution volumetric images. MR images
      provide a matching anatomical atlas for creating individualized region-of-interest templates
      for each subject.

      Subject preparation consists of two intravenous (IV) catheterizations and immobilization of
      the head. PET scans are acquired as subjects rest using an HRRT PET scanner (207 slices,
      resolution better than 3 mm FWHM). This resolution permits visualization of the PHNO and
      raclopride uptake in the ventral/dorsal striatum, in globus pallidus (GP) and substantia
      nigra (SN). A transmission scan using an orbiting 137Cs point-source is obtained for each
      emission scan. Motion correction will be performed dynamically with measurements from the
      Vicra (NDI Systems, Waterloo, Ontario) used by a dedicated list-mode reconstruction
      algorithm.
    

Intervention name(s): Amphetamine
Intervention type(s): Drug
Intervention description(s): All subjects will receive amphetamine to induce elevated dopamine levels in the brain at 0.5mg/kg
Other intervention name(s): dextro-amphetamine
Intervention MeSH terms: Amphetamine; Dextroamphetamine
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Other
Keywords: Cigarette Smokers; Healthy Non Smokers; Amphetamine; PET; Controls