PET Brain and Whole Body Distribution Studies for Nociceptin/Orphanin FQ Peptide (NOP) Receptor Using [11C]NOP-1A
Condition: Pain; Anxiety; Depression
MeSH terms: Depression
Study type: Interventional
Phase: Early Phase 1

Summary: 
      Background:

      - A small brain protein called nociceptin/orphanin FQ peptide (NOP) receptor may be involved
      in several brain diseases such as anxiety, depression, drug abuse, and seizures. Researchers
      are interested in testing a new radioactive chemical that will help locate NOP receptors in
      the brain during imaging studies such as positron emission tomography (PET) scans. Because
      this chemical has not yet been approved by the Food and Drug Administration, it is considered
      to be an experimental drug.

      Objectives:

      - To investigate the effectiveness of the experimental chemical [11C]NOP-1A in imaging
      studies of the nociceptin/orphanin FQ peptide (NOP) receptor.

      Eligibility:

      - Healthy volunteers between 18 and 50 years of age who are able to have imaging studies.

      Design:

        -  This study will involve three or four outpatient visits to the National Institutes of
           Health Clinical Center. All participants will be screened with a full physical
           examination, medical history, blood and urine tests, and electrocardiogram.

        -  Participants will be involved in one or more parts of this three-part study as directed
           by study researchers. Part 1 consists of brain imaging to study how the brain responds
           to the chemical. Part 2 is a whole body imaging study to evaluate how the chemical is
           distributed throughout the body after being administered. Part 3 is a set of testing and
           retesting scans to determine how precise the drug is in locating the NOP receptors in
           the brain.

        -  Part 1: Participants will have a brain magnetic resonance imaging (MRI) scan. Then the
           study drug will be administered and participants will have a brain PET scan. Blood
           samples will be taken during the PET scan, and urine samples will be taken after the
           scan. These tests will take up to 3 hours to perform.

        -  Part 2: Participants will have a whole body PET scan that will last a maximum of 3
           hours.

        -  Part 3: Participants will receive the study drug and have two additional PET scans.
           Blood samples will also be taken during this part.
    

Detailed description: 
      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.
    

Intervention name(s): NOP-1A
Intervention type(s): Drug
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: Nociceptin/Orphanin FQ Peptide (NOP); PET Imaging; Brain Imaging; Healthy Volunteer; HV