Nicotine Receptor Levels and Smoking Cessation

Subjects will be asked to complete a short screening session, an orientation phone call, and
two imaging sessions: one PET imaging session and one MRI session.

Intake Session. This session will familiarize subjects with the study procedures and risks,
as well as determine initial eligibility for the study. Subjects will first complete an
Imaging Screening Form with study personnel. Subjects will also complete a Magnet Safety Form
to check for any metal in the body. Finally, subjects will complete a Scanning Registration
Form.

Orientation Call. Dr. Dubroff (the Principal Investigator and study physician) will call
subjects before the PET Scan Session to review the study procedures and risks and answer any
questions subjects might have.

PET Scan Session. Subjects will receive a telephone call the day before the session to remind
them to stop smoking at 9:00pm that night. At the session, they will provide a series of
samples. These include:

- A urine sample to assess for the presence of study-prohibited drugs and medications
(including cocaine, opiates, benzodiazepines, amphetamines, methamphetamines, tri-cyclic
antidepressants, methadone, PCP, and barbiturates).

- Women of childbearing age will be required to take a urine pregnancy test.

- A breath alcohol concentration (BrAC) measurement.

- A breath carbon monoxide (CO) reading.

- Have your weight measured.

After subjects arrive at the PET center, they will have two intravenous (I.V.) lines placed.
A sterile solution will be dripped through the tubing to keep them open. Subjects will have
blood pressure and heart rate taken prior to injection and three 10ml tubes of blood will be
drawn to determine the baseline levels of radioactive tracer. After this, subjects will be
injected with a radioactive tracer (a chemical that has a radioactive molecule attached to
it) called 2-[18F]FA that will be pumped through one of the I.V. lines over an 8-hour period.
During the waiting period subjects will complete two questionnaires, a brief IQ test, and
five computer games. They will have repeated blood pressure and heart rate readings taken
soon after the initial injection and every 45 minutes afterwards. The investigators will draw
3 ml (half a teaspoon) of blood from the second I.V. line every 15-30 minutes to measure
radiotracer levels.

Just prior to beginning the scan, subjects will be asked two questions about cravings. These
questions will be asked every 30 minutes during the scan and then once more after subjects
have exited the scan. The investigators will draw one 3ml tube of blood at the beginning of
the PET scan and every 30 min during the PET scan (total 5 teaspoons) from the second I.V.
line to measure radiotracer levels.

Exclusion Criteria:

In addition to the exclusion criteria used for PNAT trial [NCT01314001], participants in
this trial will be excluded if they meet the following criteria:

Imaging-Related Exclusion Criteria:

1. Weigh over 299 lbs.

2. Self-reported history of head trauma or brain (or CNS) tumor.

3. Self-reported history of claustrophobia (contraindicated for PET and MRI).

4. Cochlear implant or bilateral hearing aids.

5. Pacemakers, certain metallic implants, or presence of metal in the eye as
contraindicated for MRI.

6. History of gunshot wound (including BB guns).

7. Circumstances or conditions that may interfere with magnetic resonance imaging (MRI).

8. CO reading greater than 15ppm at the PET Scan Session (or at least a 50% reduction
from the PNAT Intake Session).

9. BrAC reading greater than or equal to 0.01 at the PET Scan Session.

10. Positive urine drug screen for cocaine, phencyclidine, amphetamines, methamphetamines,
tricyclic antidepressants, opiates, methadone, benzodiazepines, or barbiturates at the
PNAT Intake Session or PET Scan Session.

11. Positive urine pregnancy (females only) screen at the PET Scan Session and/or MRI Scan
Session.

12. Inability to give blood at the PET Scan Session (blood samples are required to analyze
PET data).

13. Prior exposure to radioactive tracers in imaging studies or for medical reasons may be
exclusionary.

General Exclusion Criteria:

1. Any medical condition, illness, disorder or concomitant medication that could
compromise participant safety or treatment, as determined by the Principal
Investigator or Co-investigators.

2. Inability to provide informed consent or complete the study procedures within 10 hours
and/or correctly, as determined by the Principal Investigator or Co-investigators.

3. Any physical or visual impairment that would prevent completion of the cognitive
tasks.

4. Participation (within the last 6 months) in other studies at our center involving
similar cognitive testing procedures.