Abstract 6288: Evaluation of therapeutic strategy for the treatment of kidney cancer using multimodal imaging

INTRODUCTION: As the most common type of kidney cancer, renal cell carcinoma (RCC) emerges in the form of highly vascularized tumors. Our team has recently demonstrated the therapeutic effects of two novel heme-targeting agents (heme-sequestering peptide 2 (HSP2) and cyclopamine tartrate (CycT)) which effectively suppress angiogenic activities and normalize tumor vasculatures in non-small cell lung cancer (NSCLC) cells and mouse tumor models [1,2]. We have now applied non-invasive multimodal imaging to evaluate these heme related treatments of kidney cancer. METHODS: Magnetic Resonance Imaging (MRI) and MultiSpectral Optoacoustic Tomography (MSOT) are ideally suited for investigations of the kidney and RCC given their extensive vasculature. MRI was performed at 9.4-T using high-resolution axial T2-weighted multi-slice images encompassing the entire kidney tumor were obtained with a fat suppressed fast spin-echo sequence in about 8 minutes. The MSOT system illuminates the mouse from all sides, providing effective excitation (700, 780, 800, 820, 850 nm) even at depth, revealing rudimentary anatomy, as well as functional oxy- and deoxyhemoglobin. We used MSOT and MRI modalities to determine the degree to which CycT modified hypoxia in orthotopic PDX renal XP 334 tumor xenografts in mice. RESULTS: Both MSOT and MRI showed anatomical differences between treated and control tumors with treated tumors being significantly smaller (p < 0.002). Dynamic hemoglobin changes to oxygen-breathing challenge through MSOT as a response to control and CycT group in kidney tumors. CONCLUSION: MR and MSOT imaging allowed us to monitor and evaluate the effects of the novel heme targeting drugs CycT, which significantly suppressed orthotopic kidney PDX 334 tumor growth. MSOT demonstrates dynamic hemoglobin changes to oxygen-breathing challenge in response to CycT and untreated control groups in kidney tumors. Combining MR imaging with other non-invasive imaging modalities provides a clear guide on monitoring and targeting treatments for tumors in mice. REFERENCES: [1] S. Sohoni, et al., Elevated Heme Synthesis and Uptake Underpin Intensified Oxidative Metabolism and Tumorigenic Functions in Non-Small Cell Lung Cancer Cells, Cancer Res, 79 (2019) 2511-2525. [2] P. Ghosh, et al., Oxygen-Enhanced Optoacoustic Tomography Reveals the Effectiveness of Targeting Heme and Oxidative Phosphorylation at Normalizing Tumor Vascular Oxygenation, Cancer Research, 80 (2020) 3542. Acknowledgments