European journal of nuclear medicine and molecular imaging · 2026
Whole-body TSPO-PET reveals stage-dependent disruption of systemic immune organ interactions in glioblastoma.
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Mueller Gloria, Zatcepin Artem, Bartos Laura M, Hoermann Leonie, Wesser Lena, Park Ha Eun, Thevis Justus F, Haertel Marlies, Kunze Lea H, Palumbo Giovanna, Kolabas Zeynep Ilgin, Lindner Simon, Werner Rudolf A, Albert Nathalie L, von Baumgarten Louisa, Ziegler Sibylle, Brendel Matthias
Аннотация
PURPOSE: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.