Whole-body TSPO-PET reveals stage-dependent disruption of systemic immune organ interactions in glioblastoma.

Abstract

Strong expression of the 18 kDa translocator protein (TSPO) is observed in glioma and tumor-associated myeloid cells within the tumor microenvironment. However, TSPO expression also extends beyond the tumor and may reflect systemic immune regulation. We therefore assessed inter-organ associations of TSPO expression in mice at different stages of glioblastoma using whole-body TSPO-PET imaging. Whole-body TSPO-PET images were acquired using [¹⁸F]GE-180 in sham-inoculated mice (n = 18) and glioblastoma-bearing mice at early (5-13 days, n = 20) and late (18-19 days, n = 29) stages. The tumor and organs (brain, heart, lungs, skull, and various bones) were segmented to compare TSPO-PET signals between mouse cohorts. Pearson correlation served to analyze cohort-specific organ-organ interaction, and deviations were quantified using correlation abnormality scores. [¹⁸F]DPA-714 TSPO-PET scans (n = 53) of a validation cohort served for longitudinal assessment of TSPO organ-organ interaction, which was analyzed relative to tumor stage and survival. Late-stage glioblastoma mice showed increased TSPO expression in the tumor region, but no significant TSPO alterations in other organs. In contrast, organ-organ interactions, including lungs and non-tumor brain regions, were disrupted in early- and late-stage glioblastoma mice compared to sham mice. Late-stage glioblastoma mice had high correlation abnormality scores across several organ systems, as was also observed in data obtained with the second TSPO tracer. Longitudinal TSPO organ-organ interactions, but not TSPO-PET signals in single organs, were associated with tumor stage and survival. Glioblastoma induces stage-dependent systemic TSPO alterations and organ-organ interaction changes, suggesting that whole-body TSPO-PET network analysis may track tumor-associated immune dynamics.