PET Imaging of Brain Peripheral Benzodiazepine Receptors
Condition: Healthy Volunteer
Study type: Interventional
Phase: Phase 1

Summary: 
      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.
    

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.
    

Intervention name(s): [(11)C] PBR28
Intervention type(s): Drug
Primary purpose: Treatment
Keywords: Pharmacokinetics; Compartmental Analysis; Distribution Volume; Identitiability; Healthy Volunteer; HV