P12.43.B DISTAL INFLAMMATION IN NORMAL-APPEARING BRAIN AND BRAINSTEM OF POST-TREATMENT HIGH-GRADE GLIOMA PATIENTS: EVIDENCE FROM TSPO PET IMAGING

Abstract BACKGROUND High-grade gliomas (HGG) are highly aggressive and incurable brain tumours. Inflammatory components in the tumour microenvironment are linked to progression and therapy resistance. Neuroinflammation can be detected using dedicated positron emission tomography (PET) radiotracers that bind to the 18kDa translocator protein (TSPO), a biomarker attributed to microglia/macrophage activation. Studies of TSPO-PET, in tumour sites, have demonstrated an association between TSPO expression and glioma grade/survival, but the effect on regions distant from the primary tumour site remains unclear. We therefore sought to investigate TSPO binding within ‘normal’-appearing brain (NAB) regions of both newly-diagnosed and post-treatment HGG using [11C](R)PK11195 PET. MATERIAL AND METHODS Twenty-one patients (12 newly-diagnosed and 9 post-treatment) underwent MRI and [11C](R)PK11195 PET. [11C](R)PK11195 distribution volume ratio (DVR), a marker of specific binding and TSPO expression, maps were generated using the simplified reference tissue model. Brain Hammer’s atlas was used to define global, contralateral, and ipsilateral grey (GM), white matter (WM), and brainstem regions of interest. The tumour volume, delineated as FLAIR hyperintensity with an additional one-voxel margin in all directions, was excluded. RESULTS The ipsilateral cortex (GM) demonstrated significantly higher [11C](R)PK11195 BPND than the contralateral cortex in both newly diagnosed HGG (1.071 vs 1.017, p<0.001, paired test) and post-treatment HGG (1.088 vs 1.055, p<0.001, paired test). Markedly, the hemispheric difference was greater in the newly diagnosed group. On a global level, the post-treatment HGG demonstrated higher [11C](R)PK11195 BPND in brain cortex (GM, 1.066 vs. 1.043) and whole brain (GM&WM, 1.043 vs. 1.012), although the differences were not statistically significant (p>0.05, unpaired test). Notably, brainstem [11C](R)PK11195 BPND was significantly elevated in post-treatment HGG patients compared to newly-diagnosed patients (1.15 vs 1.079, p=0.014, unpaired t-test). CONCLUSION We investigated TSPO binding in NAB of newly-diagnosed and post-treatment HGG patients using [11C](R)PK11195PET. Ipsilateral cortical regions demonstrated significantly higher TSPO binding, indicating localised neuroinflammation beyond the primary tumour site. Post-treatment patients showed elevated global TSPO binding, suggesting a potential increase in neuroinflammatory burden. Critically, the significant increase in brainstem TSPO binding following treatment points to the potential for distal neuroinflammatory changes. This distal inflammatory effect may contribute to clinical decline, warranting further investigation into underlying mechanisms and potential therapeutic strategies in HGG.