Non-Invasive Differentiation of Benign Renal Tumors from Clear Cell Renal Cell Carcinomas Using Clinically Translatable Hyperpolarized (13)C Pyruvate Magnetic Resonance

Incidental detection of localized renal tumors at imaging is increasing. Conventional imaging cannot reliably differentiate the 20% of these tumors that are benign from malignant renal cell carcinomas (RCCs), leading to unnecessary surgical resection and resulting morbidity. Here, we investigated hyperpolarized (13)C pyruvate metabolism in live patient-derived renal tumor tissue slices using a novel magnetic resonance-compatible bioreactor platform. We show, for the first time, that clear cell RCCs (ccRCCs), which constitute 70%–80% of all RCCs, exhibit increased lactate production and rapid lactate efflux when compared with benign renal tumors. This difference is because of increased lactate dehydrogenase A and monocarboxylate transporter 4 expression in ccRCCs. Thus, RCCs can be differentiated from benign renal tumors by assessing this distinctive metabolic phenotype using clinically translatable hyperpolarized (13)C pyruvate magnetic resonance.