PET Evaluation of Brain Peripheral Benzodiazepine Receptors Using [11C]PBR28 in HIV-Seropositive Patients With (MCMD)

The peripheral benzodiazepine receptor (PBR) is distinct from central benzodiazepine
receptors associated with GABAa 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
[11C]1-(2-chlorophenyl-N-methylpropyl)-3-isoquinoline carboxamide (PK11195). However, this
classical ligand provides low levels of specific signal. Recently we developed a new ligand,
N-acetyl-N-(2-methoxybenzyl)-2-phenoxy-5-pyridinamine [11C]PBR28, which showed much greater
specific signal than [11C]PK11195 in non-human primates. ln the present protocol we plan to
perform a kinetic brain imaging study with [11C]PBR28 in HlV-seronegative controls,
HIV-seropositive, non-impaired patients, and HlV-seropositive patients with minor cognitive
motor disorder(MCMD). Each subject will recieve a brain-dedicated PET scan with 20
mCi[(11)C]PBR28.

- INCLUSION CRITERIA:

Inclusion criteria (healthy control subjects) aged 18 50 years with history/physical exam,
ECG, and laboratory tests, plus inclusion criteria listed will be included in the protocol.

1. HIV-seropositive based on ELISA and Western blot (except the HIV-seronegative
subjects, who will have ELISA screening).

2. Capable of providing informed consent.

3. Ambulatory at initial visit.

4. If cognitively impaired, the degree of impairment will be MCMD, and not frank
HIV-associated dementia.

EXCLUSION CRITERIA:

1. Current psychiatric illness or severe systemic disease based on history and physical
exam

2. Current dependence on alcohol or substances other than nicotine.

3. Laboratory results from blood or urine tests that show clinically significant
abnormalities.

4. Previous radiation exposure (X-rays, PET scans etc.) that would exceed research
limits.

5. Pregnancy and breast feeding.

6. A history of brain disease.

7. Cannot lie on your back for long periods since the pictures will be taken for about
2.5 hours during which time you will have to lie still on the scanner bed.

8. More than moderate hypertension.

9. Positive result on urine screen for illicit drugs.