PET Imaging of Nicotinic Acetylcholine Receptors
Condition: Healthy Volunteers; Nicotine Dependence; Pharmacokinetics
MeSH terms: Tobacco Use Disorder
Study type: Observational

Summary: 
      Background:

      - Central nicotinic acetylcholine receptors (nAChRs) are the primary target for the action of
      nicotine. In addition to being involved in tobacco dependence, they are also involved in a
      variety of brain disorders, including Alzheimer's and Parkinson's diseases. Researchers are
      interested in developing better ways to study the action of nAChRs to improve treatments for
      smoking cessation and other problems affected by these receptors. These new study methods may
      involve different radiotracers, which are drugs that can help show brain activity during
      positron emission tomography (PET) scanning.

      Objectives:

      - To evaluate the feasibility of using a radiotracer, 2-[18F]F-A-85380, in PET scanning of
      the brain.

      Eligibility:

      - Healthy volunteers between 21 and 45 years of age who do not use tobacco.

      Design:

        -  Participants will be asked to avoid consuming alcohol or using a number of
           over-the-counter medications, including antihistamines, cough medicines, and nasal
           decongestants, for 5 days before the study day. Participants provide urine and breath
           samples at the start of the study to be tested for chemicals that may interfere with the
           study.

        -  Participants will visit the clinical center the morning of the day before the scanning
           session to provide blood and urine samples as required. Participants will return and be
           admitted for an overnight stay later that afternoon or evening.

        -  On the day of the study, participants will receive a single dose of the radiotracer
           2-[18F]F-A-85380, and will have a series of PET scans over the next 7 hours and provide
           blood samples during that time. Participants will spend that night at the clinical
           center and leave on the morning after the end of the study.

        -  Participants will return for follow-up visits 2 weeks and 1 month after the end of the
           study.
    

Detailed description: 
      Background: Central nicotinic acetylcholine receptors (nAChRs) mediate a variety of brain
      functions and have been implicated in the pathophysiology of Alzheimer's and Parkinson's
      diseases, other CNS disorders (Tourette's syndrome, epilepsy, etc.), and nicotine dependence.
      These receptors are the primary target for the action of nicotine, which is believed to cause
      tobacco dependence. The availability of a suitable agent that could image nAChRs with PET in
      humans would allow scientists to monitor the nAChRs in vivo for the purpose of determining
      their roles in the pathogenesis of neurodegenerative diseases and nicotine dependence.

      Scientific Goals: The immediate goal of the proposed study is to evaluate the feasibility of
      using a radiotracer, 2-[18F]F-A-85380, developed by scientists in the NIDA Brain Imaging
      Center for external imaging of nAChRs in the human brain.

      Study Population: Healthy adult participants, males and females between 21 and 45 years of
      age, will be recruited for this study. The goal is to complete studies of 7 male and 7 female
      subjects.

      Experimental Design and Method: After being medically cleared and giving informed consent,
      participants will receive a single dose of the radiotracer, 2 [18F]F A 85380-Injection, and
      will undergo a series of PET scans acquired over the next 7 hours after the injection. The
      PET scans will be used to determine the time course of the distribution of the injected
      radioactivity in those organs expected to receive the highest radiation exposure and in the
      brain.

      Benefits to participants and/or society: This protocol will provide no direct benefits to the
      research participants other than routine medical screening and attention from the research
      staff. The knowledge gained in this study may lead to the availability of an agent for
      external monitoring of nAChRs using PET. This agent would be a valuable tool for determining
      the role of nAChRs in the pathogenesis of neuropsychiatric diseases, including nicotine
      dependence and for developing medications for diseases that respond to nicotinic agonists.

      Risks to participants: There is some risk attendant to the PET scans in general, involving
      exposure to radiation, arterial catheterization and venous catheterization. In addition,
      there is risk related to the administration of this radiopharmaceutical, as it will be given
      to humans for the first time in this study. Medical supervision will be provided throughout
      the study. A plan for monitoring potential side effects of this radiotracer is given.
    

Time perspective: Other
Keywords: Nicotinic Acetylcholine Receptors; Neuroimaging; Positron Emission Tomography (PET); Alpha4beta2; Nicotine; Receptor Upregulation