Imaging glial cell activation with [11C]-R-PK11195 in patients with AIDS.
Glial cell activation occurs in response to brain injury and is present in a wide variety of inflammatory processes including dementia associated with human immunodeficiency virus (HIV). HIV-infected glial cells release cytokines and chemokines that, along with viral neurotoxins, contribute to neuronal damage and apoptosis. The purpose of this study was to determine if glial cell activation in HIV-positive (HIV+) patients could be detected noninvasively, in vivo, using [11C]-R-PK11195 with positron emission tomography (PET). [11C]-R-PK11195 is a selective radioligand for the peripheral benzodiazepine receptor (PBR), and is known to reflect the extent of glial cell activation. A subaim was to determine if nondemented HIV+ patients could be distinguished from those with HIV-associated dementia (HAD) on the basis of [11C]-R-PK11195 binding. Five healthy volunteers and 10 HIV+ patients underwent PET with [11C]-R-PK11195. Time-radioactivity curves (TACs) were generated from dynamic PET images in nine regions of interest (ROIs) drawn on coregistered magnetic resonance imaging (MRI) scans. The average radioactivity was calculated in each ROI and was normalized to the average radioactivity in white matter. Patients with HAD showed significantly higher [11C]-R-PK11195 binding than controls in five out of eight brain regions (P < .05, Mann-Whitney U test). Nondemented HIV+ patients did not show significantly increased binding compared to controls. HIV+ patients overall (demented and nondemented) showed significantly higher radioligand binding than controls in five brain regions (P < 0.05). Patients with HAD did not show significant differences in binding when compared to HIV+ nondemented patients. The findings of this pilot study support a role for glial cell activation in HAD, and that PET with [11C]-R-PK11195 can detect the concomitants of neuronal damage in individuals infected with HIV.
Hammoud
Dima A
DA
Department of Radiology, the Johns Hopkins Medical Institutions, Baltimore, Maryland 21287-2182, USA.
Endres
Christopher J
CJ
Chander
Ankit R
AR
Guilarte
Tomas R
TR
Wong
Dean F
DF
Sacktor
Ned C
NC
McArthur
Justin C
JC
Pomper
Martin G
MG
D015526:AIDS Dementia Complex / Q000000981:diagnostic imaging* / Q000276:immunology / Q000473:pathology; D000328:Adult; D000970:Antineoplastic Agents; D001921:Brain / Q000000981:diagnostic imaging / Q000276:immunology / Q000473:pathology; D002250:Carbon Radioisotopes; D005260:Female; D006801:Humans; D007546:Isoquinolines; D008297:Male; D008875:Middle Aged; D009457:Neuroglia / Q000000981:diagnostic imaging* / Q000276:immunology / Q000821:virology; D010865:Pilot Projects; D049268:Positron-Emission Tomography / Q000379:methods*
D000970:Antineoplastic Agents; D002250:Carbon Radioisotopes; D007546:Isoquinolines; C037850:PK 11195