Imaging of Cannabinoid Receptors Using New Radioactive Tracer
Condition: Healthy
Study type: Interventional
Phase: Phase 1

Summary: 
      This study will test a new radioactive tracer, [(11)C]MePPEP, for use in positron emission
      tomography (PET) imaging. The tracer is used to visualize cannabinoid receptors, proteins in
      the brain that mediate a variety of natural chemicals. These receptors may be important in
      behavioral diseases such as addiction, obesity and psychiatric diseases.

      Healthy normal volunteers between 18 and 65 years of age may be eligible for this study.

      Ten participants undergo whole body PET imaging to determine where the [(11)C]MePPEP tracer
      is distributed in the body in order to calculate radiation exposure from the tracer. Another
      10 subjects undergo brain imaging with [(11)C]MePPEP to measure cannabinoid receptors in the
      brain.

      All participants are evaluated with a medical history and physical examination, blood and
      urine tests and an electrocardiogram (ECG) before scanning. They then have a PET scan. For
      this procedure, a catheter (plastic tube) is placed in a vein in the arm through which the
      tracer is injected. A special mask is fitted to the head and attached to the bed to help keep
      the head in place during the scan. Subjects undergoing brain imaging also have a catheter
      placed in an artery in the wrist from which blood samples are collected during the procedure.
      The scan lasts about 2 to 2.5 hours.

      Subjects undergoing brain imaging also have magnetic resonance imaging (MRI) within 1 year of
      the PET scan. For MRI, the subject lies on a bed that moves into the tubular scanner, wearing
      earplugs to protect the ears from loud noises that occur during the scan. The procedure takes
      about 1 hour.
    

Detailed description: 
      BRAIN IMAGING:

      OBJECTIVE:

      The central cannabinoid receptor, CB(1) is one of the most abundant neuromodulatory receptors
      in the brain. It is found on glutamatergic, dopaminergic and GABA-ergic synaptic terminals
      and belongs to the G-protein coupled receptor family. The CB(1) is a target for drug therapy,
      including the use of an antagonist as an appetite suppressant. The central cannabinoid
      receptor CB(1) has never been visualized in humans. In collaboration with Eli Lilly, we
      developed a promising PET ligand for the CB(1) receptor: [(11)C]MePPEP. This study is known
      by Eli Lilly as H6O-MC-GCEB.

      STUDY POPULATION:

      In the current protocol, we wish to evaluate [(11)C]MePPEP in approximately 15 healthy
      subjects.

      DESIGN:

      Brain imaging studies will consist of subject evaluation followed by PET and MRI scans.

      OUTCOME MEASURES:

      We intend to determine the kinetics of brain uptake and washout, clearance in the plasma, and
      the distribution volume of [(11)C]MePPEP calculated with compartmental modeling. Distribution
      volume is proportional to the density of receptors and is equal to the ratio at equilibrium
      of uptake in brain to the concentration of parent radiotracer in plasma.

      WHOLE BODY DOSIMETRY:

      OBJECTIVE:

      Should the brain imaging studies prove to be successful, we will continue with whole body
      dosimetry studies. Preliminary dosimetry studies with [(11)C]MePPEP have been performed in
      nonhuman primates; however, these need to be continued in humans before further investigation
      of this novel tracer can continue. This study is known by Eli Lilly as H6O-MC-GCEC.

      STUDY POPULATION:

      In the current protocol, we wish to evaluate [(11)C]MePPEP in approximately 10 additional
      healthy subjects.

      DESIGN:

      The whole body dosimetry studies will consist of subject evaluation followed by a PET scan.

      OUTCOME MEASURES:

      We intend to determine the whole body distribution of activity and thereby calculate
      radiation exposure to organs of the body.
    

Intervention name(s): [(11)C] MePPEP
Intervention type(s): Drug
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: PET; CB1 Receptor; Cannabinoid; [11C] MePPEP; Brain Imaging; Healthy Volunteer; HV