Abstract #4537

EPR imaging of oxygen consumption driven by NQO1-activated compounds in FH-deficient renal tumors

Yuki Shibata¹, Daniel R Crooks¹, Shun Kishimoto¹, Jeeva Munasinghe², Kristofer Ervin², Jeffrey Brender³, Murali C Krishna³, and William Marston Linehan¹

¹Urologic Oncology Branch, National Cancer Institute, National Institution of Health, Bethesda, MD, United States, ²National Institute of Neurological Disorders and Stroke, National Institution of Health, Bethesda, MD, United States, ³Radiation Biology Branch, National Cancer Institute, National Institution of Health, Bethesda, MD, United States

Synopsis

Keywords: Preclinical Image Analysis, Electron Paramagnetic Resonance

Motivation: Renal tumors in patients affected by Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC) are aggressive and metastasize early. The high expression of NAD(P)H quinone oxidoreductase 1 (NQO1) in HLRCC could be a therapeutic target.

Goal(s): Our goal was to determine if NQO1-activated substrates can be used as a therapeutic approach for HLRCC renal tumors.

Approach: In vitro experiments and EPR, DCE, and photoacoustic imaging were performed to study the effect of NQO1-activated substrates on oxygen levels and tumor growth in HLRCC.

Results: Our study demonstrated by EPR imaging that oxygen consumption is induced by NQO1-activated substrates, resulting in ROS production and tumor cytotoxicity.

Impact: We found that NQO1-activated substrates induced non-mitochondrial oxygen consumption in FH-deficient renal tumor cells, triggering oxidative stress-induced cancer cell death. Our results suggest a promising path for NQO1-targeted therapy in HLRCC, necessitating further research and treatment development.

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