PET Imaging of Cannabinoid CB1 Receptors Using [18F]FMPEP-d2
Condition: CB1; Cannabinoid; PET; Brain Imaging
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this protocol is to measure brain CB1 receptors in the hope to better
      understand how they work, so that one day we can understand how the CB1 receptors are
      involved in psychiatric, neurological, and behavioral disorders.
    

Detailed description: 
      BRAIN IMAGING

      Objective

      The central cannabinoid receptor (CB1) 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 G-protein coupled receptor family. The CB1 is a target for drug therapy,
      including the use of an antagonist as an appetite suppressant. The central cannabinoid
      receptor CB1 has never been visualized in humans. In collaboration with Eli Lilly, we
      developed a promising PET ligand for the CB1 receptor: [18F]FMPEP-d2
      ((3R,5R)-5-(3-(fluoromethoxy)phenyl)-3-((R)-1-phenylethylamino)-1-(4-(trifluoromethyl)phenyl)
      pyrrolidin-2-one).

      Study Population

      In the current protocol, we wish to evaluate [18F]FMPEP-d2 in approximately 10 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 [18F]FMPEP-d2 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 [18F]d2-FMPEP have been performed in
      nonhuman primates; however, these need to be continued in humans before further investigation
      of this novel tracer can continue.

      Study Population

      In the current protocol, we wish to evaluate [18F]FMPEP-d2 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.

      BRAIN IMAGING WITH TEST/RE-TEST

      Objective

      Should the brain imaging and dosimetry studies prove to be successful, we will continue with
      test/retest brain imaging studies. Test/retest studies with [18F]FMPEP-d2 will provide
      evidence of reproducibility and strengthen the assurance that this radioligand can be used to
      assess pathology. Previous investigations in developing a CB1 receptor PET tracer have
      demonstrated the need to test reproducibility (Terry, In Writing; Burns et al 2007).

      Study Population

      In the current protocol, we wish to evaluate [18F]FMPEP-d2 in approximately 10 additional
      healthy subjects.

      Design

      The brain imaging test/retest studies will consist of subject evaluation followed by one MRI
      and two PET scans.

      Outcome Measures

      We intend to determine the reproducibility of the outcome measures from the brain imaging,
      namely, distribution volume.
    

Intervention name(s): [18F]FMPEP-d2
Intervention type(s): Drug
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: CB1 Receptor; PET; Cannabinoid; [18F]FMPEP-d2; Brain Imaging; Healthy Volunteer; HV