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Detecting tumor response to treatment using hyperpolarized 13C magnetic resonance imaging and spectroscopy

Nature Medicine volume 13, pages 1382–1387 (2007)Cite this article

An Erratum to this article was published on 01 December 2007

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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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Figure 1: Flux of hyperpolarized 13C label between pyruvate and lactate in an EL-4 cell suspension.
Figure 2: Effect of addition of exogenous lactate and induction of cell death on flux of hyperpolarized 13C label between pyruvate and lactate in an EL-4 cell suspension.
Figure 3: Induction of cell death depletes EL-4 cells of NAD(H).
Figure 4: Flux of hyperpolarized 13C label between pyruvate and lactate in EL-4 tumors.
Figure 5: 13C spectroscopic imaging of EL-4 tumors before and after drug treatment.

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  • 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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Author notes

  1. Sam E Day and Mikko I Kettunen: These authors contributed equally to this work.

Authors and Affiliations

  1. Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge, CB2 0RE, UK

    Sam E Day, Mikko I Kettunen, Ferdia A Gallagher, De-En Hu & Kevin M Brindle

  2. Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge, CB2 1GA, UK

    Sam E Day, Mikko I Kettunen, Ferdia A Gallagher, De-En Hu & Kevin M Brindle

  3. Department of Radiology, University of Cambridge, Level 5, Box 219 Addenbrooke's Hospital, Hills Road, Cambridge, CB2 2QQ, UK

    Ferdia A Gallagher

  4. Imagnia AB, Box 8225 200 41, Malmö, Sweden

    Mathilde Lerche & Klaes Golman

  5. GE Healthcare, The Grove Centre GC/18, White Lion Road, Amersham, HP7 9LL, UK

    Jan Wolber & Jan Henrik Ardenkjaer-Larsen

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Contributions

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.

Corresponding author

Correspondence to Kevin M Brindle.

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Competing interests

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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