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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01198197
Recruitment Status : Completed
First Posted : September 9, 2010
Last Update Posted : June 19, 2018
Information provided by:
National Institutes of Health Clinical Center (CC)

Brief Summary:


- 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.


- To investigate the effectiveness of the experimental chemical [11C]NOP-1A in imaging studies of the nociceptin/orphanin FQ peptide (NOP) receptor.


- Healthy volunteers between 18 and 50 years of age who are able to have imaging studies.


  • 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.

Condition or disease Intervention/treatment Phase
Pain Anxiety Depression Drug: NOP-1A Early Phase 1

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 41 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: PET Brain and Whole Body Distribution Studies for Nociceptin/Orphanin FQ Peptide (NOP) Receptor Using [(11)C]NOP-1A
Study Start Date : September 3, 2010
Actual Study Completion Date : February 28, 2014

Resource links provided by the National Library of Medicine

Primary Outcome Measures :
  1. For the PET scans, we will measure the regional densities of NOP receptors as distribution volume (VT). Distribution volume is the ratio at equilibrium of brain uptake to the concentration of parent radioligand in plasma. [ Time Frame: 2 years ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Healthy Volunteers:

Subjects must be adults between 18-50 years old.

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


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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01198197

United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Institute of Mental Health (NIMH)
Principal Investigator: Masahiro Fujita, M.D. National Institute of Mental Health (NIMH)

Publications: Identifier: NCT01198197     History of Changes
Other Study ID Numbers: 100204
First Posted: September 9, 2010    Key Record Dates
Last Update Posted: June 19, 2018
Last Verified: September 5, 2014

Keywords provided by National Institutes of Health Clinical Center (CC):
Nociceptin/Orphanin FQ Peptide (NOP)
PET Imaging
Brain Imaging
Healthy Volunteer

Additional relevant MeSH terms:
Vasodilator Agents
Analgesics, Opioid
Central Nervous System Depressants
Physiological Effects of Drugs
Sensory System Agents
Peripheral Nervous System Agents