BIOM-17. EVALUATION OF CARBONIC ANHYDRASE TYPE IX (CA IX) EXPRESSION AS TARGET FOR RADIOLIGAND THERAPY IN GLIOBLASTOMA

Abstract BACKGROUND Glioblastoma represents an unmet need in neuro-oncology. Radioligand therapies are effective and approved in extracranial malignancies such as prostate cancer and neuroendocrine tumors, but data on their use is limited in brain tumors. In addition, rational target selection in gliomas is complicated by tumor heterogeneity. In extracranial tumors, clinical trials of radionuclide treatments targeting carbonic anhydrase IX (CA IX) are ongoing. METHODS Tumor samples of glioblastoma (isocitrate dehydrogenase [IDH]-wildtype) were retrieved from the Neuro-Biobank of the Medical University of Vienna. Formalin-fixed, paraffin-embedded tissue specimen were stained using rabbit anti-CA IX antibody (clone EP161, Cell Marque) on a Ventana Benchmark Ultra platform (Roche Diagnostics). CA IX expression was assessed semiquantitatively. RESULTS Overall, 29 patient samples were included in this study. Median age at surgery was 65 years (range: 55 – 74), and 22/29 (75.9%) were male. Median overall survival (OS) reached 11.6 months (95% confidence interval: 7.3 – 16.3). In total, 24/29 (82.8%) of specimen were positive for CA IX, of whom 20/29 (69.0%) exhibited moderate to high membranous CA IX expression and 4/29 (13.8%) showed weak immunoreactivity. CA IX staining displayed pronounced spatial heterogeneity, as positive areas were primarily seen in pseudo-palisading tumor cells around necrotic foci. Patients with stronger CA IX staining tended to have longer OS (median: 14.2 months) compared to those with absent or weak CA IX expression (median OS: 6.2 months; p = 0.075). Inclusion of further samples of different glioma subtypes is ongoing. CONCLUSIONS CA IX could represent a promising target for radioligand therapy in glioblastoma given the strong CA IX immunoreactivity in most samples. Intratumoral heterogeneity in CA IX expression should be considered in the design of appropriate compounds and the choice of optimal radionuclides to maximize efficacy.