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In vivo imaging of glucose uptake and metabolism in tumors

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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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Figure 1: Schematic diagram illustrating the principles underlying glucoCEST.
Figure 2: In vivo glucoCEST data from subcutaneous tumor xenograft models.
Figure 3: Comparison of glucoCEST with ex vivo [18F]FDG autoradiography and in vivo Gd-DTPA uptake.
Figure 4: Example glucoCEST, [18F]FDG autoradiography and fluorescence microscopy images obtained from the same tumor section (two LS174T and two SW1222 human colorectal xenograft models).
Figure 5: Results of [U-13C] NMR of tumor fragments and in vitro z spectra of the sugars and amino acids identified from them.

Change history

  • 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.

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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.

Corresponding author

Correspondence to Simon Walker-Samuel.

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Supplementary Figures 1–7 and Supplementary Methods (PDF 1008 kb)

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Walker-Samuel, S., Ramasawmy, R., Torrealdea, F. et al. In vivo imaging of glucose uptake and metabolism in tumors. Nat Med 19, 1067–1072 (2013). https://doi.org/10.1038/nm.3252

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