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

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.