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

Abstract

Dynamic nuclear polarization can be used to increase the sensitivity of solution state (13)C magnetic resonance spectroscopy by four orders of magnitude. We show here that [1-(13)C]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 (13)C 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.

• Authors: Ferdia A Gallagher, Mikko I Kettunen, Sam E Day, De-en Hu, Magnus Karlsson, Anna Gisselsson, Mathilde H Lerche, Kevin M Brindle
• Journal: Magnetic resonance in medicine (Magn Reson Med) Vol. 66 Issue 1 Pg. 18-23 (Jul 2011) ISSN: 1522-2594 [Electronic] United States
• PMID: 21695718 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Wiley-Liss, Inc.

Chemical References

• Carbon Isotopes
• Ketoglutaric Acids
• Glutamic Acid
• Pyruvic Acid
• Alanine Transaminase

Topics

• Alanine Transaminase (metabolism)
• Animals
• Carbon Isotopes (metabolism)
• Cell Survival
• Disease Models, Animal
• Glutamic Acid (chemistry, metabolism)
• Hep G2 Cells
• Humans
• Ketoglutaric Acids (metabolism)
• Lymphoma (metabolism)
• Magnetic Resonance Spectroscopy
• Mice
• Pyruvic Acid (metabolism)