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The effect of hyperpolarized tracer concentration on myocardial uptake and metabolism
Author(s) -
Schroeder Marie A.,
Atherton Helen J.,
Cochlin Lowri E.,
Clarke Kieran,
Radda George K.,
Tyler Damian J.
Publication year - 2009
Publication title -
magnetic resonance in medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.696
H-Index - 225
eISSN - 1522-2594
pISSN - 0740-3194
DOI - 10.1002/mrm.21934
Subject(s) - chemistry , hyperpolarization (physics) , pyruvate dehydrogenase complex , enzyme , in vivo , allosteric regulation , alanine , lactate dehydrogenase , metabolism , nuclear magnetic resonance , biochemistry , nuclear magnetic resonance spectroscopy , amino acid , biology , stereochemistry , physics , microbiology and biotechnology
Hyperpolarized 13 C‐labeled substrates directly provide a source of magnetic resonance (MR) signal to observe the substrates' real‐time uptake and enzymatic conversion. The aim of this study was to optimize the concentration of hyperpolarized [1‐ 13 C]pyruvate infused as a metabolic tracer, by observing the mitochondrial conversion of pyruvate to H 13 CO 3 − in heart tissue. Hyperpolarized pyruvate was infused into rats at concentrations between 20 mM and 80 mM and the relationships between [1‐ 13 C]lactate, [1‐ 13 C]alanine, and H 13 CO 3 − production and the infused pyruvate concentration were investigated. H 13 CO 3 − production reached saturation above 40 mM infused pyruvate concentration, indicating that hyperpolarized MR experiments performed at this concentration maximize the H 13 CO 3 − signal with minimal alterations to in vivo substrate composition. Additionally, the linear dependence of alanine production on pyruvate concentration confirmed that hyperpolarized MR methods in the heart reveal enzyme activity, rather than cellular uptake. H 13 CO 3 − production demonstrated evidence of sigmoidal enzyme kinetics, a reflection of the allosteric nature of the pyruvate dehydrogenase (PDH) enzyme complex. This protocol could be useful to optimize the infused concentration of other hyperpolarized metabolites in different organs, to ensure adequate MR signal with minimum metabolic perturbation. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.