Abstract #4724

EPR oximetry using Ox071 detects acute kidney injury induced by cyclophosphamide

Shun Kishimoto¹, Chandramouli Gadisetti², Nallathamby Devasahayam³, Kazumasa Horie³, Kota Yamashita³, Kazutoshi Yamamoto³, Hellmut Merkle⁴, Jeffrey R. Brender³, Daniel R Crooks³, Murali C Krishna³, and W. Marston Linehan³

¹NCI, BETHESDA, MD, United States, ²Genepria, Rockville, MD, United States, ³NCI, Bethesda, MD, United States, ⁴NINDS, Bethesda, MD, United States

Synopsis

Keywords: Electron Paramagnetic Resonance, Oxygenation, EPR oximetry, Ox071

Motivation: EPR oximetry using Ox071 holds promise in detecting chemotherapy-induced acute kidney injury by monitoring pO₂ distribution.

Goal(s): Using EPR, our study assessed the ability to discern pO₂ variations between healthy kidneys and kidney injury models induced by intraperitoneal cyclophosphamide treatment.

Approach: To validate these changes, we performed ex vivo histological assessments with pimonidazole staining, comparing these results with EPR based pO₂ maps.

Results: Analysis of the hypoxic fraction in tumor tissues via pimonidazole staining revealed a transient reduction at 2 days post-treatment, followed by recovery at 30 days. EPR oximetry results consistently mirrored these trends, affirming its reliability as a non-invasive method.

Impact: Historically, EPR oximetry focused on tumor hypoxia due to Ox063's limitations in well-oxygenated tissues. Using Ox071, a deuterated analog, current research extends oximetry to normoxic tissues, notably the kidneys.

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