Detection of tumor glutamate metabolism in vivo using 13C magnetic resonance spectroscopy and hyperpolarized [1- 13C]glutamate

Ferdia A. Gallagher, Mikko I. Kettunen, Sam E. Day, De En Hu, Magnus Karlsson, Anna Gisselsson, Mathilde Hauge Lerche, Kevin M. Brindle

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Dynamic nuclear polarization can be used to increase the sensitivity of solution state 13C magnetic resonance spectroscopy by four orders of magnitude. We show here that [1- 13C]glutamate can be polarized to 28%, representing a 35,000-fold increase in its sensitivity to detection at 9.4 T and 37°C. The metabolism of hyperpolarized glutamate to α-ketoglutarate, catalyzed by the enzyme alanine transaminase, was detected in vitro in human hepatoma cells (HepG2). Incubation of the cells with sodium pyruvate increased the level of the hyperpolarized label in the α-ketoglutarate pool, with an associated increase in the apparent rate constant describing flux of hyperpolarized 13C label between glutamate and α-ketoglutarate. The metabolism of hyperpolarized glutamate was observed in vivo following coadministration of pyruvate in a murine lymphoma model. This represents a new method to probe glutamate metabolism and citric acid cycle activity in vivo; as glutamate is an endogenous molecule, it has the potential to be used in the clinic. Magn Reson Med, 2011. © 2011 Wiley-Liss, Inc. Copyright © 2011 Wiley-Liss, Inc.
Original languageEnglish
JournalMagnetic Resonance in Medicine
Volume66
Issue number1
Pages (from-to)18-23
ISSN0740-3194
DOIs
Publication statusPublished - 2011
Externally publishedYes

Keywords

  • Alanine Transaminase
  • Animals
  • Carbon Isotopes
  • Cell Survival
  • Disease Models, Animal
  • Glutamic Acid
  • Hep G2 Cells
  • Humans
  • Ketoglutaric Acids
  • Lymphoma
  • Magnetic Resonance Spectroscopy
  • Mice
  • Pyruvic Acid
  • alpha-ketoglutaric acid
  • Radiology, Nuclear Medicine and Imaging
  • α-ketoglutarate
  • alanine transaminase
  • glutamate
  • hyperpolarized 13C
  • pyruvate
  • 2 oxoglutaric acid
  • alanine aminotransferase
  • carbon 13
  • gadolinium chelate
  • glutamic acid
  • pyruvate sodium
  • trometamol
  • amino acid metabolism
  • animal experiment
  • animal model
  • article
  • carbon nuclear magnetic resonance
  • citric acid cycle
  • dynamic nuclear polarization
  • enzyme mechanism
  • hepatoma cell
  • human
  • human tissue
  • hyperpolarization
  • in vivo study
  • lymphoma cell
  • mouse
  • nonhuman
  • polarization
  • tumor diagnosis

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