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Probing Lactate Dehydrogenase Activity in Tumors by Measuring Hydrogen/Deuterium Exchange in Hyperpolarized l-[1-(13)C,U-(2)H]Lactate

[Image: see text] (13)C magnetic resonance spectroscopy and spectroscopic imaging measurements of hyperpolarized (13)C label exchange between exogenously administered [1-(13)C]pyruvate and endogenous lactate, catalyzed by lactate dehydrogenase (LDH), has proved to be a powerful approach for probing...

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Autores principales: Kennedy, Brett W. C., Kettunen, Mikko I., Hu, De-En, Brindle, Kevin M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2012
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3303201/
https://www.ncbi.nlm.nih.gov/pubmed/22316419
http://dx.doi.org/10.1021/ja300222e
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author Kennedy, Brett W. C.
Kettunen, Mikko I.
Hu, De-En
Brindle, Kevin M.
author_facet Kennedy, Brett W. C.
Kettunen, Mikko I.
Hu, De-En
Brindle, Kevin M.
author_sort Kennedy, Brett W. C.
collection PubMed
description [Image: see text] (13)C magnetic resonance spectroscopy and spectroscopic imaging measurements of hyperpolarized (13)C label exchange between exogenously administered [1-(13)C]pyruvate and endogenous lactate, catalyzed by lactate dehydrogenase (LDH), has proved to be a powerful approach for probing tissue metabolism in vivo. This experiment has clinical potential, particularly in oncology, where it could be used to assess tumor grade and response to treatment. A limitation of the method is that pyruvate must be administered in vivo at supra-physiological concentrations. This problem can be avoided by using hyperpolarized [1-(13)C]lactate, which can be used at physiological concentrations. However, sensitivity is limited in this case by the relatively small pyruvate pool size, which would result in only low levels of labeled pyruvate being observed even if there was complete label equilibration between the lactate and pyruvate pools. We demonstrate here a more sensitive method in which a doubly labeled lactate species can be used to measure LDH-catalyzed exchange in vivo. In this experiment exchange of the C2 deuterium label between injected hyperpolarized l-[1-(13)C,U-(2)H]lactate and endogenous unlabeled lactate is observed indirectly by monitoring phase modulation of the spin-coupled hyperpolarized (13)C signal in a heteronuclear (1)H/(13)C spin–echo experiment.
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spelling pubmed-33032012012-03-14 Probing Lactate Dehydrogenase Activity in Tumors by Measuring Hydrogen/Deuterium Exchange in Hyperpolarized l-[1-(13)C,U-(2)H]Lactate Kennedy, Brett W. C. Kettunen, Mikko I. Hu, De-En Brindle, Kevin M. J Am Chem Soc [Image: see text] (13)C magnetic resonance spectroscopy and spectroscopic imaging measurements of hyperpolarized (13)C label exchange between exogenously administered [1-(13)C]pyruvate and endogenous lactate, catalyzed by lactate dehydrogenase (LDH), has proved to be a powerful approach for probing tissue metabolism in vivo. This experiment has clinical potential, particularly in oncology, where it could be used to assess tumor grade and response to treatment. A limitation of the method is that pyruvate must be administered in vivo at supra-physiological concentrations. This problem can be avoided by using hyperpolarized [1-(13)C]lactate, which can be used at physiological concentrations. However, sensitivity is limited in this case by the relatively small pyruvate pool size, which would result in only low levels of labeled pyruvate being observed even if there was complete label equilibration between the lactate and pyruvate pools. We demonstrate here a more sensitive method in which a doubly labeled lactate species can be used to measure LDH-catalyzed exchange in vivo. In this experiment exchange of the C2 deuterium label between injected hyperpolarized l-[1-(13)C,U-(2)H]lactate and endogenous unlabeled lactate is observed indirectly by monitoring phase modulation of the spin-coupled hyperpolarized (13)C signal in a heteronuclear (1)H/(13)C spin–echo experiment. American Chemical Society 2012-02-09 2012-03-14 /pmc/articles/PMC3303201/ /pubmed/22316419 http://dx.doi.org/10.1021/ja300222e Text en Copyright © 2012 American Chemical Society http://pubs.acs.org This is an open-access article distributed under the ACS AuthorChoice Terms & Conditions. Any use of this article, must conform to the terms of that license which are available at http://pubs.acs.org.
spellingShingle Kennedy, Brett W. C.
Kettunen, Mikko I.
Hu, De-En
Brindle, Kevin M.
Probing Lactate Dehydrogenase Activity in Tumors by Measuring Hydrogen/Deuterium Exchange in Hyperpolarized l-[1-(13)C,U-(2)H]Lactate
title Probing Lactate Dehydrogenase Activity in Tumors by Measuring Hydrogen/Deuterium Exchange in Hyperpolarized l-[1-(13)C,U-(2)H]Lactate
title_full Probing Lactate Dehydrogenase Activity in Tumors by Measuring Hydrogen/Deuterium Exchange in Hyperpolarized l-[1-(13)C,U-(2)H]Lactate
title_fullStr Probing Lactate Dehydrogenase Activity in Tumors by Measuring Hydrogen/Deuterium Exchange in Hyperpolarized l-[1-(13)C,U-(2)H]Lactate
title_full_unstemmed Probing Lactate Dehydrogenase Activity in Tumors by Measuring Hydrogen/Deuterium Exchange in Hyperpolarized l-[1-(13)C,U-(2)H]Lactate
title_short Probing Lactate Dehydrogenase Activity in Tumors by Measuring Hydrogen/Deuterium Exchange in Hyperpolarized l-[1-(13)C,U-(2)H]Lactate
title_sort probing lactate dehydrogenase activity in tumors by measuring hydrogen/deuterium exchange in hyperpolarized l-[1-(13)c,u-(2)h]lactate
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3303201/
https://www.ncbi.nlm.nih.gov/pubmed/22316419
http://dx.doi.org/10.1021/ja300222e
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