Pilot imaging of the colony stimulating factor 1 receptor in the brains of virally-suppressed individuals with HIV

Objective: Neuroimmune activation is a putative driver of cognitive impairment in people with HIV (PWH), even in the age of modern antiretroviral therapy. Nevertheless, imaging of the microglial marker, the 18kDa translocator protein (TSPO), with positron emission tomography (PET) in treated PWH has yielded inconclusive findings. One potential reason for the varied TSPO results is a lack of cell-type specificity of the TSPO target. Design: [11C]CPPC is a radiotracer for use with PET to image the colony stimulating factor 1 receptor (CSF1R). The CSF1R is expressed on microglia and central nervous system macrophages, with little expression on other cell types. We used [11C]CPPC PET in virally- §Corresponding author: Jennifer Marie Coughlin 600 N. Wolfe Street, Meyer 3-181, Baltimore, 21287, USA, 443-287-4701, jcoughl2@jhmi.edu. *These authors have contributed equally to the work. Authors’ contributions LR, YD, AGH, MP, and JC jointly developed the concept of the manuscript. LR, YD, SES, RO, CH, KJ, WL, RV, RD, JS, HF, DH, AWH, RFD, AGH, MP, and JC each contributed to data acquisition. LR, YD, WL, and RD led the analysis, with AGH, MP, and JC contributing to interpretation of the findings. All authors were involved in the writing and proof reading of the manuscript. List of Supplemental Digital Content Supplemental Digital Content 1.doc Competing interests Under a license agreement between D&D Pharmatech and the Johns Hopkins University, the University, AGH, and MGP are entitled to royalty distributions related to the technology described in the study. MGP is a founder of and holds equity in D&D Pharmatech. He also is a paid consultant to the company. AGH is a paid consultant to the company. As the spouse of MGP, JMC shares his disclosures. This arrangement has been reviewed and approved by the Johns Hopkins University in accordance with its conflict of interest policies. HHS Public Access Author manuscript AIDS. Author manuscript; available in PMC 2024 July 15. Published in final edited form as: AIDS. 2023 July 15; 37(9): 1419–1424. doi:10.1097/QAD.0000000000003572. Author Manuscript Author Manuscript Author Manuscript Author Manuscript suppressed- (VS)-PWH and HIV-uninfected individuals to estimate the effect sizes of higher CSF1R in the brains of VS-PWH. Methods: Sixteen VS-PWH and 15 HIV-uninfected individuals completed [11C]CPPC PET. [11C]CPPC binding (VT) in nine regions was estimated using a one-tissue compartmental model with a metabolite-corrected arterial input function, and compared between groups. Results: Regional [11C]CPPC VT did not significantly differ between groups after age- and sex- adjustment (unstandardized beta coefficient [B]=1.84, standard error [SE]=1.18, P=0.13). The effect size was moderate (Cohen’s d=0.56, 95%confidence interval [CI] −0.16, 1.28), with strongest trend of higher VT in VS-PWH in striatum and parietal cortex (each P=0.04; Cohen’s d=0.71 and 0.72 respectively). Conclusions: Group difference in [11C]CPPC VT was not observed between VS-PWH and HIV-uninfected individuals in this pilot, although the observed effect sizes suggest the study was underpowered to detect regional group differences in binding.