Regional brain distribution of translocator protein using [ 11C]DPA-713 PET in individuals infected with HIV

Jennifer Marie Coughlin, Yuchuan Wang, Shuangchao Ma, Chen Yue, Pearl K. Kim, Ashley V. Adams, Heidi V. Roosa, Kenneth L. Gage, Marigo Stathis, Rana Rais, Camilo Rojas, Jennifer L. McGlothan, Crystal Watkins, Ned Sacktor, Tomas R. Guilarte, Yun Zhou, Akira Sawa, Barbara Slusher, Brian S Caffo, Michael Kassiou & 2 others Christopher J. Endres, Martin Gilbert Pomper

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)219-232
Number of pages14
JournalJournal of NeuroVirology
Volume20
Issue number3
DOIs
StatePublished - 2014

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Positron-Emission Tomography
HIV
Gyrus Cinguli
Brain
Neuroglia
Healthy Volunteers
Proteins
AIDS Dementia Complex
Parietal Lobe
Frontal Lobe
Neuroimaging
Biomarkers
N,N-diethyl-2-(2-(4-methoxyphenyl)-5,7-dimethyl-pyrazolo(1,5-a)pyrimidin-3-yl)-acetamide
Therapeutics
Gray Matter

Keywords

  • HIV-associated neurocognitive disorder
  • Microglia
  • Molecular neuroimaging
  • Neuro aids
  • Neuroinflammation
  • Translocator protein

ASJC Scopus subject areas

  • Virology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Neurology

Cite this

Regional brain distribution of translocator protein using [ 11C]DPA-713 PET in individuals infected with HIV. / Coughlin, Jennifer Marie; Wang, Yuchuan; Ma, Shuangchao; Yue, Chen; Kim, Pearl K.; Adams, Ashley V.; Roosa, Heidi V.; Gage, Kenneth L.; Stathis, Marigo; Rais, Rana; Rojas, Camilo; McGlothan, Jennifer L.; Watkins, Crystal; Sacktor, Ned; Guilarte, Tomas R.; Zhou, Yun; Sawa, Akira; Slusher, Barbara; Caffo, Brian S; Kassiou, Michael; Endres, Christopher J.; Pomper, Martin Gilbert.

In: Journal of NeuroVirology, Vol. 20, No. 3, 2014, p. 219-232.

Research output: Contribution to journalArticle

Coughlin, Jennifer Marie ; Wang, Yuchuan ; Ma, Shuangchao ; Yue, Chen ; Kim, Pearl K. ; Adams, Ashley V. ; Roosa, Heidi V. ; Gage, Kenneth L. ; Stathis, Marigo ; Rais, Rana ; Rojas, Camilo ; McGlothan, Jennifer L. ; Watkins, Crystal ; Sacktor, Ned ; Guilarte, Tomas R. ; Zhou, Yun ; Sawa, Akira ; Slusher, Barbara ; Caffo, Brian S ; Kassiou, Michael ; Endres, Christopher J. ; Pomper, Martin Gilbert. / Regional brain distribution of translocator protein using [ 11C]DPA-713 PET in individuals infected with HIV. In: Journal of NeuroVirology. 2014 ; Vol. 20, No. 3. pp. 219-232.
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AU - Kim, Pearl K.

AU - Adams, Ashley V.

AU - Roosa, Heidi V.

AU - Gage, Kenneth L.

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AU - Rojas, Camilo

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AU - Watkins, Crystal

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