Non-Invasive Differentiation of Benign Renal Tumors from Clear Cell Renal Cell Carcinomas Using Clinically Translatable Hyperpolarized ¹³C 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 ¹³C 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 ¹³C pyruvate magnetic resonance.