PET Brain and Whole Body Distribution Studies for Nociceptin/Orphanin FQ Peptide (NOP) Receptor Using [11C]NOP-1A

Nociceptin/orphanin FQ peptide (NOP) receptor is a new class of opioid receptor cloned in 1994 before identifying the endogenous ligand. Within a year, endogenous ligand was identified and soon many ligands were developed and evaluated in vitro and in vivo for NOP receptor distribution and activity. NOP receptor is widely distributed in brain, spinal cord and in peripheral organs such as heart, lungs, kidney, intestine and liver. Being a G-protein coupled receptor, its activation leads to changes in intracellular signal transduction mediated by adenylyl cyclase, Ca(2+) and K(+) ion channels, mitogen-activated kinase and phospholipase C. Based on preclinical studies, NOP receptor is implicated in regulation of pain, anxiety and depression, drug abuse, feeding, learning/memory, and motor activity.

Since the time of cloning the receptor and identification of endogenous ligand, numerous compounds have been designed targeting this receptor. However, there are no PET radioligands currently available to study NOP distribution and activity in humans. We wish to test a newly developed PET radioligand, [(11)C]NOP-1A to study the role of NOP receptors in humans.

The purpose of this protocol is (1) to perform brain imaging using [(11)C]NOP-1A in healthy volunteers to characterize the brain uptake and distribution (2) to perform whole body PET studies in healthy volunteers in order to estimate radiation absorbed doses for [(11)C]NOP-1A, (3) to perform brain test-retest studies in healthy volunteers in order to further examine the precision of the measurement of receptor binding and to determine optimal parameters for future experiments using [(11)C]NOP-1A, and, (4) to compare [(11)C]NOP-1A concentrations in artery and vein of healthy volunteers to assess the feasibility of replacing the arterial line with a less invasive venous line for brain scans.

Successful development of a PET radioligand to image NOP receptor will have a strong impact on further understanding and clinical management of neuropsychiatric disorders that are mediated by opioid receptor system. Future experiments will include studies on any relevant neuropsychiatric disorder.

• INCLUSION CRITERIA:

Healthy Volunteers:

Subjects must be adults between 18-50 years old.

Subjects must be able and willing to give written informed consent.

Exclusion criteria

Current psychiatric illness or severe systemic disease based on history and physical exam.

If women, pregnancy or breast feeding (betaHCG will be measured in all female patients within 24 hours of scan and must be negative)

Clinically significant laboratory abnormalities.

Serious medical problems including but not limited to chronic neurological disease such as multiple sclerosis, autoimmune diseases or any cardiopulmonary disease.

Head trauma resulting in a period of unconsciousness lasting longer than 10 minutes.

Recent exposure to radiation (i.e., PET from other research) which when combined with this study would be above the allowable limits.

Positive urine drug screen at screening.

Inability to lie flat on camera bed for about 2.5 hours

Subjects who have metallic foreign bodies that would be affected by the MRI magnet, or fear of enclosed spaces likely to make the subject unable to undergo an MRI scan.