Abstract
Measurements of early tumor responses to therapy have been shown, in some cases, to predict treatment outcome. We show in lymphoma-bearing mice injected intravenously with hyperpolarized [1-13C]pyruvate that the lactate dehydrogenase–catalyzed flux of 13C label between the carboxyl groups of pyruvate and lactate in the tumor can be measured using 13C magnetic resonance spectroscopy and spectroscopic imaging, and that this flux is inhibited within 24 h of chemotherapy. The reduction in the measured flux after drug treatment and the induction of tumor cell death can be explained by loss of the coenzyme NAD(H) and decreases in concentrations of lactate and enzyme in the tumors. The technique could provide a new way to assess tumor responses to treatment in the clinic.
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Change history
12 November 2007
In the version of this article initially published, Equation 2 was incorrect. Additionally, peak 1 in Figure 1a was incorrectly defined in the figure legend. The errors have been corrected in the HTML and PDF versions of the article.
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Acknowledgements
F.A.G. received a Cancer Research UK and Royal College of Radiologists (UK) clinical research training fellowship, and S.E.D. received a US National Institutes of Health–Cambridge studentship. This work was supported by a Cancer Research UK programme grant to K.M.B. (C197/A3514). The polarizer and related materials were provided by GE Healthcare.
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S.E.D. conducted the cell experiments and operated the polarizer with F.A.G. M.I.K. was responsible for MRS and imaging experiments. S.E.D., F.A.G. and M.I.K. were jointly responsible for data analysis. D.-E.H. was responsible for tumor implantation and animal handling during the MRS experiments. M.L., J.W., K.G. and J.H.A.-L. provided advice and assistance with the pyruvate preparation and operation of the polarizer. K.M.B. organized the study, devised the kinetics analysis and wrote the paper.
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The hyperpolarizer is on loan from GE Healthcare and is the subject of a research agreement between the University of Cambridge and GE Healthcare. GE Healthcare also supplied the 13C-labeled pyruvate and the trityl radical used in the hyperpolarization process.
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Supplementary Figs. 1–5, Supplementary Data, and Supplementary Methods (PDF 684 kb)
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Day, S., Kettunen, M., Gallagher, F. et al. Detecting tumor response to treatment using hyperpolarized 13C magnetic resonance imaging and spectroscopy. Nat Med 13, 1382–1387 (2007). https://doi.org/10.1038/nm1650
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DOI: https://doi.org/10.1038/nm1650
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