TY - JOUR
T1 - Regional brain distribution of translocator protein using [ 11C]DPA-713 PET in individuals infected with HIV
AU - Coughlin, Jennifer M.
AU - Wang, Yuchuan
AU - Ma, Shuangchao
AU - Yue, Chen
AU - Kim, Pearl K.
AU - Adams, Ashley V.
AU - Roosa, Heidi V.
AU - Gage, Kenneth L.
AU - Stathis, Marigo
AU - Rais, Rana
AU - Rojas, Camilo
AU - McGlothan, Jennifer L.
AU - Watkins, Crystal C.
AU - Sacktor, Ned
AU - Guilarte, Tomas R.
AU - Zhou, Yun
AU - Sawa, Akira
AU - Slusher, Barbara S.
AU - Caffo, Brian
AU - Kassiou, Michael
AU - Endres, Christopher J
AU - Pomper, Martin G.
N1 - Funding Information:
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.
PY - 2014/6
Y1 - 2014/6
N2 - 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.
AB - 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.
KW - HIV-associated neurocognitive disorder
KW - Microglia
KW - Molecular neuroimaging
KW - Neuro aids
KW - Neuroinflammation
KW - Translocator protein
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U2 - 10.1007/s13365-014-0239-5
DO - 10.1007/s13365-014-0239-5
M3 - Article
C2 - 24567030
AN - SCOPUS:84905407732
SN - 1355-0284
VL - 20
SP - 219
EP - 232
JO - Journal of neurovirology
JF - Journal of neurovirology
IS - 3
ER -