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

✍ Scribed by Ferdia A. Gallagher; Mikko I. Kettunen; Sam E. Day; De-en Hu; Magnus Karlsson; Anna Gisselsson; Mathilde H. Lerche; Kevin M. Brindle

Publisher
John Wiley and Sons
Year
2011
Tongue
English
Weight
274 KB
Volume
66
Category
Article
ISSN
0740-3194

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✦ Synopsis

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. Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.

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