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Abstract #4538

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

Kazumasa Horie1, Shun Kishimoto1, Kota Yamashita1, Kazutoshi Yamamoto1, Jeffery R Brender1, Nallanthamby Devasahayam1, Hellmut Merkle2, Murali C Krishna1, and W Marston Linehan1
1NCI, Bethesda, MD, United States, 2NINDS, Bethesda, MD, United States

Synopsis

Keywords: Preclinical Image Analysis, Electron Paramagnetic Resonance

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.

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Keywords