title: Hyperpolarized 13C-pyruvate magnetic resonance reveals rapid lactate export in metastatic renal cell carcinomas.
abstract: Renal cell carcinomas (RCC) are a heterogeneous group of tumors with a wide range of aggressiveness. Noninvasive methods to confidently predict the tumor biologic behavior and select appropriate treatment are lacking. Here, we investigate the dynamic metabolic flux in living RCC cells using hyperpolarized (13)C-pyruvate magnetic resonance spectroscopy (MRS) combined with a bioreactor platform and interrogated the biochemical basis of the MRS data with respect to cancer aggressiveness. RCC cells have significantly higher pyruvate-to-lactate flux than the normal renal tubule cells. Furthermore, a key feature distinguishing the localized from the metastatic RCC cells is the lactate efflux rate, mediated by the monocarboxylate transporter 4 (MCT4). The metastatic RCC cells have significantly higher MCT4 expression and corresponding higher lactate efflux, which is essential for maintaining a high rate of glycolysis. We show that such differential cellular transporter expression and associated metabolic phenotype can be noninvasively assessed via real-time monitoring of hyperpolarized (13)C-pyruvate-to-lactate flux.
authors.affiliation: Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA 94158, USA. kayvan.keshari@ucsf.edu
authors.forename: Kayvan R
authors.initials: KR
authors.lastname: Keshari
authors.forename: Renuka
authors.initials: R
authors.lastname: Sriram
authors.forename: Bertram L
authors.initials: BL
authors.lastname: Koelsch
authors.forename: Mark
authors.initials: M
authors.lastname: Van Criekinge
authors.forename: David M
authors.initials: DM
authors.lastname: Wilson
authors.forename: John
authors.initials: J
authors.lastname: Kurhanewicz
authors.forename: Zhen J
authors.initials: ZJ
authors.lastname: Wang
mesh_terms: D002247:Carbon Isotopes; D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000473:pathology; D002460:Cell Line; D045744:Cell Line, Tumor; D006019:Glycolysis; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D009362:Neoplasm Metastasis; D019289:Pyruvic Acid / Q000378:metabolism
chemical_list: D002247:Carbon Isotopes; D019344:Lactic Acid; D019289:Pyruvic Acid