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Abstract

Tumors have a greater reliance on anaerobic glycolysis for energy production than normal tissues. We developed a noninvasive method for imaging glucose uptake in vivo that is based on magnetic resonance imaging and allows the uptake of unlabeled glucose to be measured through the chemical exchange of protons between hydroxyl groups and water. This method differs from existing molecular imaging methods because it permits detection of the delivery and uptake of a metabolically active compound in physiological quantities. We show that our technique, named glucose chemical exchange saturation transfer (glucoCEST), is sensitive to tumor glucose accumulation in colorectal tumor models and can distinguish tumor types with differing metabolic characteristics and pathophysiologies. The results of this study suggest that glucoCEST has potential as a useful and cost-effective method for characterizing disease and assessing response to therapy in the clinic.

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  • 19 July 2013

     In the version of this article initially published online, the water molecules in Figure 1a had two oxygens and one hydrogen, rather than two hydrogens and one oxygen. The errors have been corrected for all versions of this article.

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Acknowledgements

This work was funded by King's College London and UCL Comprehensive Cancer Imaging Centre, and The Institute of Cancer Research Cancer Imaging Centre, Cancer Research UK and EPSRC in association with the Medical Research Council (MRC), the Department of Health (England) (C1060/A10334, C1519/A10331, C16412/A6269 and C309/A8274) and the British Heart Foundation and was supported by researchers at the National Institute for Health Research UCL Hospital Biomedical Research Centre.

Author information

Author notes

    • Mark F Lythgoe
    •  & Xavier Golay

    These authors jointly directed this work.

Affiliations

  1. University College London (UCL) Centre for Advanced Biomedical Imaging, Division of Medicine and Institute of Child Health, London, UK.

    • Simon Walker-Samuel
    • , Rajiv Ramasawmy
    • , Francisco Torrealdea
    • , Simon Richardson
    • , Miguel Gonçalves
    •  & Mark F Lythgoe
  2. UCL Institute of Neurology, London, UK.

    • Francisco Torrealdea
    • , Marilena Rega
    • , David L Thomas
    •  & Xavier Golay
  3. UCL Cancer Institute, London, UK.

    • Vineeth Rajkumar
    • , S Peter Johnson
    •  & R Barbara Pedley
  4. Cancer Research UK and Engineering and Physical Sciences Research Council (EPSRC) Cancer Imaging Centre, The Institute of Cancer Research and Royal Marsden National Health Service Foundation Trust, Sutton, Surrey, UK.

    • Harold G Parkes
  5. Department of Chemistry, UCL, London, UK.

    • Erik Årstad

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Contributions

S.W.-S. designed and performed experiments, analyzed data, developed the methodology and wrote the paper. R.R. performed glucose tail-vein measurements, assisted with in vivo experiments and developed the arterial spin labeling (ASL) post-processing software. F.T. and M.R. performed most phantom experiments and analyzed data. S.P.J. and R.B.P. developed and set up tumor xenograft models. V.R. performed histology and autoradiography measurements and analyzed data. H.G.P. performed 13C NMR experiments. S.R. designed the bespoke apparatus for in vivo imaging. M.G. assisted with in vivo experiments. D.L.T., E.A., R.B.P., X.G. and M.F.L. gave conceptual advice and assisted in the design of experiments. X.G. devised the initial glucoCEST concept and experiment. X.G. and M.F.L. jointly directed this research, helped perform experiments and contributed to the writing and editing of this manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Simon Walker-Samuel.

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DOI

https://doi.org/10.1038/nm.3252

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