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Cited by 301

The DOI matches its Crossref record; 27 of the 27 references it cites were found in a registry or an index.

Production of hyperpolarized [1,4- 13 C 2 ]malate from [1,4- 13 C 2 ]fumarate is a marker of cell necrosis and treatment response in tumors

Open access
Gallagher, Ferdia A., Kettunen, Mikko I., Hu, De-En, Jensen, Pernille R., Zandt, René in ‘t, Karlsson, Magnus, Gisselsson, Anna, Nelson, Sarah K., Witney, Timothy H., Bohndiek, Sarah E., Hansson, Georg, Peitersen, Torben, Lerche, Mathilde H., Brindle, Kevin M.·2009·Proceedings of the National Academy of Sciences

Abstract

Dynamic nuclear polarization of 13 C-labeled cell substrates has been shown to massively increase their sensitivity to detection in NMR experiments. The sensitivity gain is sufficiently large that if these polarized molecules are injected intravenously, their spatial distribution and subsequent conversion into other cell metabolites can be imaged. We have used this method to image the conversion of fumarate to malate in a murine lymphoma tumor in vivo after i.v. injection of hyperpolarized [1,4- 13 C 2 ]fumarate. In isolated lymphoma cells, the rate of labeled malate production was unaffected by coadministration of succinate, which competes with fumarate for transport into the cell. There was, however, a correlation with the percentage of cells that had lost plasma membrane integrity, suggesting that the production of labeled malate from fumarate is a sensitive marker of cellular necrosis. Twenty-four hours after treating implanted lymphoma tumors with etoposide, at which point there were significant levels of tumor cell necrosis, there was a 2.4-fold increase in hyperpolarized [1,4- 13 C 2 ]malate production compared with the untreated tumors. Therefore, the formation of hyperpolarized 13 C-labeled malate from [1,4- 13 C 2 ]fumarate appears to be a sensitive marker of tumor cell death in vivo and could be used to detect the early response of tumors to treatment. Given that fumarate is an endogenous molecule, this technique has the potential to be used clinically.

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Metadata

Authors
Gallagher, F. A., Kettunen, M. I., Hu, D.-E., Jensen, P. R., Zandt, R. I. ‘., Karlsson, M., Gisselsson, A., Nelson, S. K., Witney, T. H., Bohndiek, S. E., Hansson, G., Peitersen, T., Lerche, M. H., & Brindle, K. M.
Venue
Proceedings of the National Academy of Sciences
Published
2009-11-24
Volume
106
Issue
47
Pages
19801-19806
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2016200811
Cited by
301
References
27
FWCI
8.79
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Production of hyperpolarized [1,4- 13 C 2 ]malate from [1,4- 13 C 2 ]fumarate is a marker of cell necrosis and treatment response in tumors. https://app.cochat.ai/papers/10.1073/pnas.0911447106
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Gallagher, F. A., Kettunen, M. I., Hu, D.-E., Jensen, P. R., Zandt, R. I. ‘., Karlsson, M., Gisselsson, A., Nelson, S. K., Witney, T. H., Bohndiek, S. E., Hansson, G., Peitersen, T., Lerche, M. H., & Brindle, K. M. (2009). Production of hyperpolarized [1,4- 13 C 2 ]malate from [1,4- 13 C 2 ]fumarate is a marker of cell necrosis and treatment response in tumors. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0911447106

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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