Imaging glial cell activation with [¹¹C]-R-PK11195 in patients with AIDS

Abstract

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.

The high affinity peripheral benzodiazepine receptor ligand DAA1106 binds to activated and infected brain macrophages in areas of synaptic degeneration: Implications for PET imaging of neuroinflammation in lentiviral encephalitis

“…However, translation of these studies to human subjects has been less promising. [ 11 C](R)-PK11195 PET retention in the brain did not differ between HIV infected patients on retroviral drugs with and without neurological deficits (Hammoud et al, 2005. These findings may be in part due to decreased brain inflammation seen in neurologically impaired HIV infected subjects on antiretroviral therapy (ART) without frank dementia (Gray et al, 2003b, Gray et al, 2003a.…”

The Role of Medical Imaging in Defining CNS Abnormalities Associated with HIV-Infection and Opportunistic Infections

“…However, the function of the dopamine D2 receptor, prominent in the basal ganglia, is evidently not affected. Increased monocyte activation in the frontal lobes, measured using a labeled benzodiazopene receptor ligand ([ 11 C]PK11195), has also been implicated in the neuropathology of HIV-associated dementia [88]. As additional substrates for PET imaging are explored, additional neuronal injury caused by HIV infection will no doubt be uncovered.…”

Quantification of (R)-[11C]PK11195 binding in rheumatoid arthritis

“…In the brain, (R)- [ 11 C]PK11195 binds to activated microglia [7] which are part of the brain's immune system. (R)- [ 11 C] PK11195 has been used extensively to image brain inflammation using PET [8][9][10][11][12][13][14][15][16]. Methods have been published regarding the quantification of (R)- [ 11 C] PK11195 binding in the brain [17][18][19].…”