title: Regional brain distribution of translocator protein using [(11)C]DPA-713 PET in individuals infected with HIV.
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, [(11)C]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, [(11)C]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.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Coughlin
authors.forename: Yuchuan
authors.initials: Y
authors.lastname: Wang
authors.forename: Shuangchao
authors.initials: S
authors.lastname: Ma
authors.forename: Chen
authors.initials: C
authors.lastname: Yue
authors.forename: Pearl K
authors.initials: PK
authors.lastname: Kim
authors.forename: Ashley V
authors.initials: AV
authors.lastname: Adams
authors.forename: Heidi V
authors.initials: HV
authors.lastname: Roosa
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: Gage
authors.forename: Marigo
authors.initials: M
authors.lastname: Stathis
authors.forename: Rana
authors.initials: R
authors.lastname: Rais
authors.forename: Camilo
authors.initials: C
authors.lastname: Rojas
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: McGlothan
authors.forename: Crystal C
authors.initials: CC
authors.lastname: Watkins
authors.forename: Ned
authors.initials: N
authors.lastname: Sacktor
authors.forename: Tomas R
authors.initials: TR
authors.lastname: Guilarte
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhou
authors.forename: Akira
authors.initials: A
authors.lastname: Sawa
authors.forename: Barbara S
authors.initials: BS
authors.lastname: Slusher
authors.forename: Brian
authors.initials: B
authors.lastname: Caffo
authors.forename: Michael
authors.initials: M
authors.lastname: Kassiou
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Endres
authors.forename: Martin G
authors.initials: MG
authors.lastname: Pomper
mesh_terms: D015526:AIDS Dementia Complex / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000628:therapy; D000081:Acetamides; D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism / Q000821:virology; D002247:Carbon Isotopes; D005838:Genotype; D006801:Humans; D017628:Microglia / Q000378:metabolism; D008875:Middle Aged; D009483:Neuropsychological Tests; D010641:Phenotype; D049268:Positron-Emission Tomography / Q000379:methods*; D011720:Pyrazoles; D011743:Pyrimidines; D018079:Receptors, GABA / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
chemical_list: D000081:Acetamides; D044966:Anti-Retroviral Agents; D015415:Biomarkers; D002247:Carbon Isotopes; C507091:N,N-diethyl-2-(2-(4-methoxyphenyl)-5,7-dimethyl-pyrazolo(1,5-a)pyrimidin-3-yl)-acetamide; D011720:Pyrazoles; D011743:Pyrimidines; D018079:Receptors, GABA; C499229:TSPO protein, human