title: 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.affiliation: Cancer Research UK Cambridge Research Institute and Department of Biochemistry, University of Cambridge, United Kingdom.
authors.forename: Ferdia A
authors.initials: FA
authors.lastname: Gallagher
authors.forename: Mikko I
authors.initials: MI
authors.lastname: Kettunen
authors.forename: Sam E
authors.initials: SE
authors.lastname: Day
authors.forename: De-en
authors.initials: DE
authors.lastname: Hu
authors.forename: Magnus
authors.initials: M
authors.lastname: Karlsson
authors.forename: Anna
authors.initials: A
authors.lastname: Gisselsson
authors.forename: Mathilde H
authors.initials: MH
authors.lastname: Lerche
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Brindle
mesh_terms: D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D002247:Carbon Isotopes / Q000378:metabolism; D002470:Cell Survival; D004195:Disease Models, Animal; D018698:Glutamic Acid / Q000737:chemistry / Q000378:metabolism*; D056945:Hep G2 Cells; D006801:Humans; D007656:Ketoglutaric Acids / Q000378:metabolism; D008223:Lymphoma / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D019289:Pyruvic Acid / Q000378:metabolism
chemical_list: D002247:Carbon Isotopes; D007656:Ketoglutaric Acids; D018698:Glutamic Acid; D019289:Pyruvic Acid; D000410:Alanine Transaminase