PET Imaging of Peripheral Benzodiazepine Receptors in Patients With Carotid Atherosclerosis

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: NCT00547976
Recruitment Status : Completed
First Posted : October 23, 2007
Last Update Posted : April 27, 2012
Information provided by:
National Institutes of Health Clinical Center (CC)

Brief Summary:
Inflammation in the vascular wall is important in atherosclerosis and the blockage of the artery. The peripheral benzodiazepine receptor is involved in inflammation and in this protocol we will attempt to take pictures, using PET camera, of inflammation in patients with atherosclerosis and compare those of healthy people.

Condition or disease Intervention/treatment Phase
Atherosclerosis Healthy Drug: [C-11]PBR28 Phase 1

Detailed Description:


Inflammation in the vascular wall plays an important role in the pathophysiology of atherosclerosis, including development of plaque, plaque destabilization and rupture. Clinical and basic scientific data demonstrate the importance of peripheral white blood cells in this process. Therefore, a noninvasive method to detect inflammatory activity in atherosclerosis may be of great value to help determine prognosis, direct therapy and perhaps assess novel therapies for stabilization of atherosclerotic plaque.

The peripheral benzodiazepine receptor (PBR) is distinct from central benzodiazepine receptors associated with GABAA receptors and has been associated with immune function. PBR is expressed in macrophages, therefore, they may be a clinically useful marker to detect inflammation. Our preliminary autoradiographic data demonstrate specific PBR binding in carotid atherosclerosis samples. Though PBR has been imaged in vivo with positron emission tomography (PET) using [(11)C]1-(2-chlorophenyl-N-methylpropyl)-3-isoquinoline carboxamide (PK11195), we developed a new ligand, [(11)C]N-acetyl-N-(2-methoxybenzyl)-2-phenoxy-5-pyridinamine (PBR28) that shows greater specific signal than [(11)C]PK11195 in non-human primates.

The objective of this protocol is to assess the utility of [(11)C]PBR28 PET to detect inflammation in unstable atherosclerosis plaques and large vessels with inflammation.

Study population

Twenty patients with carotid atherosclerosis, 20 patients with large vessel vasculitis including Takayasu's and Giant Cell arteritis, and 20 age-matched healthy subjects will have one PET scan.


A [(11)C]PBR28 PET scan and a [18 F] fluorodeoxyglucose (FDG) PET scan will be performed in patients with carotid atherosclerosis. If the patient has endarterectomy after the PET scan, endarterectomy samples will be evaluated by in vitro autoradiography using [3H]PK 11195 and immunohistological staining with macrophage markers. Patients with large vessel vasculitis and healthy subjects will also have a [(11)C]PBR28 PET scan [18 F]FDG PET scan.

Outcome measures

Binding of [(11)C]PBR28 in atherosclerotic lesions, aortic arch and its branches will be compared with the binding in the contralateral carotid artery and those in healthy subjects. Binding of [(11)C]PBR28 will also be compared with accumulation of [18 F]FDG in each region. In addition, if the patients with atherosclerosis have endarterectomy, the binding in the atherosclerotic lesions will be compared with immunohistological staining of macrophage markers.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 5 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: PET Imaging of Peripheral Benzodiazepine Receptors in Patients With Carotid Atherosclerosis
Study Start Date : October 2007
Actual Primary Completion Date : August 2009
Actual Study Completion Date : August 2009

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Atherosclerosis

Primary Outcome Measures :
  1. Binding of [11C]PBR28 at peripheral benzodiazepine receptor [ Time Frame: 3 years ]

Secondary Outcome Measures :
  1. PET [F-18]FDG uptake [ Time Frame: 3 years ]

Information from the National Library of Medicine

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, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years to 89 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Age 18 - 89

Ability to provide written informed consent


Severe systemic disease based on history, physical examination or laboratory tests that would prevent participation in the study

Prior participation in other research protocols in the last year such that radiation exposure would exceed the annual guideline of RSC

Pregnancy and breast feeding


Inability to lie flat for a few hours for the PET scans

Medically unstable

The blood glucose level is greater than 150 mg/dL after fasting

Any other condition which in the opinion of the PI would prevent satisfactory participation in and completion of the study.

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): NCT00547976

United States, Maryland
Suburban Hospital
Bethesda, Maryland, United States, 20814
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Institute of Mental Health (NIMH)

Responsible Party: Robert B. Innis, M.D./National Institute of Mental Health, National Institutes of Health Identifier: NCT00547976     History of Changes
Other Study ID Numbers: 080006
First Posted: October 23, 2007    Key Record Dates
Last Update Posted: April 27, 2012
Last Verified: April 2012

Keywords provided by National Institutes of Health Clinical Center (CC):
Unstable Plaque

Additional relevant MeSH terms:
Carotid Artery Diseases
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases