PET Imaging of Brain Peripheral Benzodiazepine Receptors

This study has been completed.
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00283920
First received: January 29, 2006
Last updated: October 3, 2007
Last verified: October 2007
  Purpose

This study will use positron emission tomography (PET) and magnetic resonance imaging (MRI) to measure peripheral benzodiazepine receptors (PBRs) in the brain. PBRs were initially found in peripheral organs such as kidneys, endocrine glands and lungs, but later studies identified PBRs in the CNS. PBRs can be a marker to detect nervous system inflammation. Development of a test to image PBRs may improve the management of brain disorders such as multiple sclerosis, Alzheimer's disease, Parkinson's disease, and others in which inflammation is involved in progression of the disease.

Healthy volunteers from 18 to 40 years old may be eligible for this study. Candidates are screened with tests that may include some or all of the following: diagnostic interview; ratings of mood, anxiety, functioning, and other parameters; neuropsychological testing; physical examination; electrocardiogram; blood and urine tests; and personal, social and family histories.

Participants undergo the following procedures:

  • Evaluation: Subjects provide a medical history, including detailed questions about their psychological health, and have a physical examination and blood and urine tests.
  • PET scanning: PET uses small amounts of a radioactive chemical called a tracer that "labels" active areas of the brain. The tracer used in this study is [11C]PBR28. For the procedure, the subject lies on the scanner bed. A special mask is fitted to the head and attached to the bed to help keep the head still during the scan so the images will be clear. A brief scan is done just before the radioactive tracer is injected to provide measures of the brain that will help to precisely calculate information from subsequent scans. After the tracer is injected through a catheter (plastic tube) placed in the arm, pictures are taken for 2 to 3 hours, during which the subject lies still on the scanner bed. Subjects return to the clinic the following day for more blood and urine sample collections.
  • MRI: The MRI scan is done within 1 year of the PET scan (either before or after the PET). MRI uses magnetic fields and radio waves to produce images of the brain. The patient lies on a table that is moved into the scanner (a narrow cylinder), wearing earplugs to muffle loud knocking and thumping sounds that occur during the scanning process. He or she can communicate with the staff at all times during the procedure.

Condition Intervention Phase
Healthy Volunteer
Drug: [(11)C] PBR28
Phase 1

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: PET Imaging of Brain Peripheral Type Benzodiazepine Receptors

Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment: 25
Study Start Date: January 2006
Estimated Study Completion Date: October 2007
Detailed Description:

The peripheral benzodiazepine receptor (PBR) is distinct from central benzodiazepine receptors associated with GABA(A) receptors. Although PBR was initially identified in peripheral organs such as kidneys, endocrine glands and lungs, later studies identified PBR in the central nervous system. In normal conditions, PBR is expressed in low levels in some neurons and glial cells. PBR can be a clinically useful marker to detect neuroinflammation because activated microglial cells in inflammatory areas express much greater levels of PBR than in microglial cells in resting conditions.

PBR has been imaged with positron emission tomography (PET) using [(11)C]1-(2-chlorophenyl-N-methylpropyl)-3-isoquinoline carboxamide (PK11195). However, this classical ligand provides only low levels of specific signals and is not sensitive to detect changes occurred in vivo. Recently we developed a new ligand, N-acetyl-N-(2-methoxybenzyl)-2-phenoxy-5-pyridinamine [(11)C]PBR28, which showed much greater specific signals than [(11)C]PK11195 in non-human primates. In the present protocol, we plan to perform a kinetic brain imaging study in healthy human subjects to measure PBR in brain regions with [(11)C]PBR28. Successful development of a PET ligand to image PBR will have a strong impact on clinical management of brain disorders with inflammation such as multiple sclerosis and ischemia and neurodegenerative disorders such as Alzheimer's and Parkinson's disease where inflammation is involved in the disease progression.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria
  • INCLUSION CRITERIA:

    1. All subjects must be healthy and aged 18-65 years.

EXCLUSION CRITERIA:

  1. Current psychiatric illness, substance abuse or severe systemic disease based on history and physical exam.
  2. ECG with clinically significant abnormalities. Any existing physical exam and ECG within one year will be reviewed and if none already exists in the chart, these will be obtained and reviewed.
  3. Laboratory tests with clinically significant abnormalities.
  4. Prior participation in other research protocols or clinical care in the last year such that radiation exposure would exceed the annual limits.
  5. Pregnancy and breast feeding.
  6. Claustrophobia.
  7. Presence of ferromagnetic metal in the body or heart pacemaker.
  8. Positive HIV test.
  9. A history of brain disease.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00283920

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00283920     History of Changes
Other Study ID Numbers: 060073, 06-M-0073
Study First Received: January 29, 2006
Last Updated: October 3, 2007
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Pharmacokinetics
Compartmental Analysis
Distribution Volume
Identitiability
Healthy Volunteer
HV

ClinicalTrials.gov processed this record on September 18, 2014