Magnetic resonance imaging of tumor glycolysis using hyperpolarized 13C-labeled glucose

Nature Medicine volume 20, pages93–97(2014)Cite this article

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Abstract

In this study, we monitored glycolysis in mouse lymphoma and lung tumors by measuring the conversion of hyperpolarized [U-2H, U-13C]glucose to lactate using 13C magnetic resonance spectroscopy and spectroscopic imaging. We observed labeled lactate only in tumors and not in surrounding normal tissue or other tissues in the body and found that it was markedly decreased at 24 h after treatment with a chemotherapeutic drug. We also detected an increase in a resonance assigned to 6-phosphogluconate in the pentose phosphate pathway. This technique could provide a new way of detecting early evidence of tumor treatment response in the clinic and of monitoring tumor pentose phosphate pathway activity.

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Figure 1: [U-2H, U-13C]glucose signals are detectable in vivo.
Figure 2: 13C spectroscopic imaging showing the spatial distribution of labeled glucose and lactate.
Figure 3: 13C MR spectrum from an untreated subcutaneous EL4 lymphoma tumor.

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Acknowledgements

The work was supported by a Cancer Research UK Programme grant (C197/A3514) and by a Translational Research Program Award from The Leukemia & Lymphoma Society to K.M.B. T.B.R. is a recipient of an Intra-European Marie Curie (FP7-PEOPLE-2009-IEF, Imaging Lymphoma) fellowship and a Long-term European Molecular Biology Organization (EMBO-ALT-1145-2009) fellowship. E.M.S. is a recipient of a fellowship from the European Union Seventh Framework Programme (FP7/2007-2013) under the Marie Curie Initial Training Network METAFLUX (project number 264780). E.M.S. acknowledges the educational support of Programme for Advanced Medical Education from Calouste Gulbenkian Foundation, Champalimaud Foundation, Ministerio de Saude and Fundacao para a Ciencia e Tecnologia, Portugal. The polarizer and related materials were provided by GE Healthcare. The authors thank F. Gallagher for help with the polarizer. The laboratory is a member of and receives support from the Cancer Research UK & Engineering and Physical Science Research Council Cancer Imaging Center in Cambridge and Manchester.

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Author notes

  1. Mikko I Kettunen and Kevin M Brindle: These authors contributed equally to this work.

Affiliations

  1. Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK
    • Tiago B Rodrigues
    • , Eva M Serrao
    • , Mikko I Kettunen
    •  & Kevin M Brindle
  2. Department of Biochemistry, University of Cambridge, Cambridge, UK
    • Brett W C Kennedy
    • , De-En Hu
    • , Mikko I Kettunen
    •  & Kevin M Brindle
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Contributions

T.B.R. and M.I.K. designed the research; T.B.R., E.M.S., B.W.C.K., D.-E.H. and M.I.K. performed the research; T.B.R. and M.I.K. analyzed data; and T.B.R., M.I.K. and K.M.B. 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, Cancer Research UK and GE Healthcare.

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Rodrigues, T., Serrao, E., Kennedy, B. et al. Magnetic resonance imaging of tumor glycolysis using hyperpolarized 13C-labeled glucose. Nat Med 20, 93–97 (2014) doi:10.1038/nm.3416

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