Abstract
Imaging the brain distribution of translocator protein (TSPO), a putative biomarker for glial cell activation and neuroinflammation, may inform management of individuals infected with HIV by uncovering regional abnormalities related to neurocognitive deficits and enable non-invasive therapeutic monitoring. Using the second-generation TSPO-targeted radiotracer, [11C]DPA-713, we conducted a positron emission tomography (PET) study to compare the brains of 12 healthy human subjects to those of 23 individuals with HIV who were effectively treated with combination antiretroviral therapy (cART). Compared to PET data from age-matched healthy control subjects, [11C]DPA-713 PET of individuals infected with HIV demonstrated significantly higher volume-of-distribution (VT) ratios in white matter, cingulate cortex, and supramarginal gyrus, relative to overall gray matter VT, suggesting localized glial cell activation in susceptible regions. Regional TSPO abnormalities were evident within a sub-cohort of neuro-asymptomatic HIV subjects, and an increase in the VT ratio within frontal cortex was specifically linked to individuals affected with HIV-associated dementia. These findings were enabled by employing a gray matter normalization approach for PET data quantification, which improved test–retest reproducibility, intra-class correlation within the healthy control cohort, and sensitivity of uncovering abnormal regional findings.
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Abbreviations
- HAND:
-
HIV-associated neurocognitive disorder
- HAD:
-
HIV-associated dementia
- cART:
-
Combination antiretroviral therapy
- TSPO:
-
Translocator protein
- PET:
-
Positron emission tomography
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Acknowledgments
We acknowledge NIH 5R21MH082277, NIH 5R01MH092443, NIH R01EB012547, NIEHS ES007062, NIH 5T32EB006351, the Lupus Foundation for America and NFL Charities for financial support. We are also grateful to Alimamy Kargbo for performing PET metabolite analyses, to Dean Wong, M.D., Ph.D. for sharing his knowledge and ideas, and to the Johns Hopkins PET Center for provision of the radiotracer.
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NIH 5R21MH082277, NIH 5R01MH092443, NIH R01EB012547, NIH 5T32EB006351, NIEHS ES007062, Lupus Foundation of America, NFL Charities.
Coughlin and Wang equally contributed to this work.
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Coughlin, J.M., Wang, Y., Ma, S. et al. Regional brain distribution of translocator protein using [11C]DPA-713 PET in individuals infected with HIV. J. Neurovirol. 20, 219–232 (2014). https://doi.org/10.1007/s13365-014-0239-5
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DOI: https://doi.org/10.1007/s13365-014-0239-5