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.