EPR imaging assessment of reduced tumor oxygenation induced by HIF-2a inhibitor Belzutifan in VHL-deficient renal cell carcinoma models

Motivation: In the previous study, EPR oximetry unveiled physiological responses to a VEGF inhibitor, but the potential of EPR oximetry in upstream inhibition of the HIF pathway remained unclear. Goal(s): To determine if Belzutifan, a HIF-2α inhibitor, affects tumor oxygenation as measured by EPR oximetry and to offer a non-invasive biomarker of its therapeutic efficacy. Approach: Three xenograft models of clear cell carcinoma were treated with Belzutifan and changes in tumor oxygen levels were assessed using EPR oximetry. Results: We observed significant alterations in tumor oxygenation exclusively in responding tumors, which we attributed to diminished VEGF expression. Impact: This research underlines the significance of EPR oximetry as a non-invasive tool to detect early responses to HIF-2α inhibitors like Belzutifan, which could profoundly affect the management and therapeutic approach for cancer treatment, guiding personalized medicine.