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

National Institutes of Health (NIH)

Status: Terminated

Conditions: HIV-Dementia; HIV-Associated Cognitive Motor Complex; Healthy; AIDS-Related Dementia Complex; AIDS Dementia Complex; HIV Infections; AIDS Encephalopathy

Treatments: Drug: [11C]PBR28

Study type: Interventional

Funder types: NIH

Identifiers

NCT00459693

070129

07-M-0129

Details and patient eligibility

About

The purpose of this protocol is to measure a receptor in the brain using positron emission tomography (PET) that is involved in inflammation.

Full description

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.

Enrollment: 40 patients

Sex: All

Ages: 18 to 50 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

• 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.