title: Non-invasive differentiation of benign renal tumors from clear cell renal cell carcinomas using clinically translatable hyperpolarized13C pyruvate magnetic resonance.
abstract: Localized renal tumors are increasingly detected incidentally at imaging. 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 associated with surgery. Here, we investigated hyperpolarized13C pyruvate metabolism in live patient-derived renal tumor tissue slices using a novel magnetic resonance (MR) -compatible bioreactor platform. We demonstrated for the first time that clear cell RCCs (ccRCCs), which account for 70-80% of all RCCs, have increased lactate production as well as rapid lactate efflux compared to benign renal tumors. This difference is attributed to increased lactate dehydrogenase A and monocarboxylate transporter 4 expression in ccRCCs. This distinctive metabolic phenotype can be used to differentiate RCCs from benign renal tumors using clinically translatable hyperpolarized13C pyruvate MR.
authors.affiliation: Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, United States.
authors.forename: Renuka
authors.initials: R
authors.lastname: Sriram
authors.affiliation: Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, United States.
authors.forename: Mark
authors.initials: M
authors.lastname: Van Criekinge
authors.affiliation: Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, United States.
authors.forename: Justin
authors.initials: J
authors.lastname: DeLos Santos
authors.affiliation: Radiology and Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY, United States.
authors.forename: Kayvan R
authors.initials: KR
authors.lastname: Keshari
authors.affiliation: Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, United States.
authors.forename: David M
authors.initials: DM
authors.lastname: Wilson
authors.affiliation: Department of Urology, Stanford University, Stanford, CA, United States.
authors.forename: Donna
authors.initials: D
authors.lastname: Peehl
authors.affiliation: Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, United States.
authors.forename: John
authors.initials: J
authors.lastname: Kurhanewicz
authors.affiliation: Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, United States.
authors.forename: Zhen J
authors.initials: ZJ
authors.lastname: Wang
keywords: Hyperpolarized 13C magnetic resonance (HP 13C MR); aerobic glycolysis; dynamic nuclear polarization (DNP); lactate efflux; patient-derived tissue slice cultures; renal cell carcinoma (RCC)