Evaluation of LDH-A and glutaminase inhibition in vivo by hyperpolarized 13C-pyruvate magnetic resonance spectroscopy of tumors

Prasanta Dutta, Quy Hoa Le Thi, David L. Vander Jagt, Takashi Tsukamoto, Gary V. Martinez, Chi V. Dang, Robert J. Gillies

Research output: Contribution to journalArticle

Abstract

Hyperpolarized 13C 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 13C-pyruvate to lactate in murine xenografts of P493 human lymphoma. In contrast, a glutaminase inhibitor reduced conversion of 13C-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.

Original languageEnglish (US)
Pages (from-to)4190-4195
Number of pages6
JournalCancer Research
Volume73
Issue number14
DOIs
StatePublished - Jul 15 2013

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Glutaminase
Pyruvic Acid
Magnetic Resonance Spectroscopy
Lactic Acid
Biomarkers
Neoplasms
Heterografts
Alanine
Lymphoma
lactate dehydrogenase 5
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Evaluation of LDH-A and glutaminase inhibition in vivo by hyperpolarized 13C-pyruvate magnetic resonance spectroscopy of tumors. / Dutta, Prasanta; Le Thi, Quy Hoa; Vander Jagt, David L.; Tsukamoto, Takashi; Martinez, Gary V.; Dang, Chi V.; Gillies, Robert J.

In: Cancer Research, Vol. 73, No. 14, 15.07.2013, p. 4190-4195.

Research output: Contribution to journalArticle

Dutta, Prasanta ; Le Thi, Quy Hoa ; Vander Jagt, David L. ; Tsukamoto, Takashi ; Martinez, Gary V. ; Dang, Chi V. ; Gillies, Robert J. / Evaluation of LDH-A and glutaminase inhibition in vivo by hyperpolarized 13C-pyruvate magnetic resonance spectroscopy of tumors. In: Cancer Research. 2013 ; Vol. 73, No. 14. pp. 4190-4195.
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