PET Imaging of Peripheral Benzodiazepine Receptors in Patients With Carotid Atherosclerosis
Condition: Atherosclerosis; Healthy
MeSH terms: Carotid Artery Diseases; Atherosclerosis
Study type: Interventional
Phase: Phase 1

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.
    

Detailed description: 
      Objective

      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.

      Design

      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.
    

Intervention name(s): [C-11]PBR28
Intervention type(s): Drug
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: Inflammation; Unstable Plaque; Macrophage; Thrombosis; Autoradiography; Atherosclerosis; Vasculitis