title: Evaluation of LDH-A and glutaminase inhibition in vivo by hyperpolarized 13C-pyruvate magnetic resonance spectroscopy of tumors.
abstract: Hyperpolarized (13)C magnetic resonance spectroscopy provides a unique opportunity to detect real-time metabolic fluxes as a means to measure metabolic treatment responses in vivo. Here, we show that pharmacologic inhibition of lactate dehydrogenase-A suppressed the conversion of hyperpolarized (13)C-pyruvate to lactate in murine xenografts of P493 human lymphoma. In contrast, a glutaminase inhibitor reduced conversion of (13)C-pyruvate to alanine without affecting conversion of pyruvate to lactate. These results illustrate the ability to monitor biomarkers for responses to antimetabolic therapy in real-time, paving the way for clinical development of imaging biomarkers to monitor metabolic pharmacodynamics.
authors.affiliation: Department of Cancer Imaging and Metabolism, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
authors.forename: Prasanta
authors.initials: P
authors.lastname: Dutta
authors.forename: Anne
authors.initials: A
authors.lastname: Le
authors.forename: David L
authors.initials: DL
authors.lastname: Vander Jagt
authors.forename: Takashi
authors.initials: T
authors.lastname: Tsukamoto
authors.forename: Gary V
authors.initials: GV
authors.lastname: Martinez
authors.forename: Chi V
authors.initials: CV
authors.lastname: Dang
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Gillies
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D002247:Carbon Isotopes / Q000378:metabolism*; D045744:Cell Line, Tumor; D005972:Glutaminase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000080864:Lactate Dehydrogenase 5; D019344:Lactic Acid / Q000378:metabolism; D008223:Lymphoma / Q000188:drug therapy* / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D051379:Mice; D019289:Pyruvic Acid / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000964:Antimetabolites, Antineoplastic; D002247:Carbon Isotopes; D007527:Isoenzymes; D019344:Lactic Acid; D019289:Pyruvic Acid; D007770:L-Lactate Dehydrogenase; D000080864:Lactate Dehydrogenase 5; D005972:Glutaminase