This article has been updated


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.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

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.


  1. 1.

    & Determination of pH using water protons and chemical exchange dependent saturation transfer (CEST). Magn. Reson. Med. 44, 799–802 (2000).

  2. 2.

    et al. Progress and promise of FDG-PET imaging for cancer patient management and oncologic drug development. Clin. Cancer Res. 11, 2785–2808 (2005).

  3. 3.

    et al. Imaging of glucose uptake in breast tumors using non-labeled D-glucose. Proceedings of the 19th Scientific Meeting, International Society for Magnetic Resonance in Medicine, 551 (Montreal, 2011).

  4. 4.

    , , , & Assessment of tumour glucose uptake using gluco-CEST. Proceedings of the 19th Scientific Meeting, International Society for Magnetic Resonance in Medicine, 182 (Montreal, 2011).

  5. 5.

    et al. Predicting response to radioimmunotherapy from the tumor microenvironment of colorectal carcinomas. Cancer Res. 67, 11896–11905 (2007).

  6. 6.

    , , , & Quantitative description of proton exchange processes between water and endogenous and exogenous agents for WEX, CEST, and APT experiments. Magn. Reson. Med. 51, 945–952 (2004).

  7. 7.

    , , , & Extracranial measurements of amide proton transfer using exchange-modulated point-resolved spectroscopy (EXPRESS). NMR Biomed. 25, 829–834 (2012).

  8. 8.

    , & Evaluation of response to treatment using DCE-MRI: the relationship between initial area under the gadolinium curve (IAUGC) and quantitative pharmacokinetic analysis. Phys. Med. Biol. 51, 3593–3602 (2006).

  9. 9.

    , , , & High-resolution 13C nuclear magnetic resonance studies of glucose metabolism in Escherichia coli. Proc. Natl. Acad. Sci. USA 75, 3742–3746 (1978).

  10. 10.

    , , & Estimation of glucose carbon recycling in children with glycogen storage disease: A 13C NMR study using [U-13C]glucose. Proc. Natl. Acad. Sci. USA 86, 4690–4694 (1989).

  11. 11.

    , & Simultaneous in vivo monitoring of hepatic glucose and glucose-6-phosphate by (13)C-NMR spectroscopy. Magn. Reson. Med. 44, 556–562 (2000).

  12. 12.

    et al. Fundamental limitations of [18F]2-deoxy-2-fluoro-D-glucose for assessing myocardial glucose uptake. Circulation 91, 2435–2444 (1995).

  13. 13.

    & The hallmarks of cancer. Cell 100, 57–70 (2000).

  14. 14.

    & Tumor metabolic rates in sarcoma using FDG PET. J. Nucl. Med. 39, 250–254 (1998).

  15. 15.

    Quantitative Analysis in Nuclear Medicine Imaging (Springer, 2005).

  16. 16.

    , , , & In vivo imaging of the dynamics of glucose uptake in the cytosol of COS-7 cells by fluorescent nanosensors. J. Biol. Chem. 278, 19127–19133 (2003).

  17. 17.

    , , & Dynamic modulation of intracellular glucose imaged in single cells using a FRET-based glucose nanosensor. Pflugers Arch. 456, 307–322 (2008).

  18. 18.

    , , , & Amide proton transfer (APT) contrast for imaging of brain tumors. Magn. Reson. Med. 50, 1120–1126 (2003).

  19. 19.

    , , , & Using the amide proton signals of intracellular proteins and peptides to detect pH effects in MRI. Nat. Med. 9, 1085–1090 (2003).

  20. 20.

    et al. Analysis of the regional uptake of radiolabeled deoxyglucose analogs in human tumor xenografts. J. Nucl. Med. 45, 101–107 (2004).

  21. 21.

    et al. Improving apparent diffusion coefficient estimates and elucidating tumour heterogeneity using Bayesian adaptive smoothing. Magn. Reson. Med. 65, 438–447 (2011).

  22. 22.

    , & Intrascanner and interscanner variability of magnetization transfer-sensitized balanced steady-state free precession imaging. Magn. Reson. Med. 65, 1112–1117 (2011).

  23. 23.

    , , & Magnetization transfer with echo planar imaging. MAGMA 5, 259–265 (1997).

  24. 24.

    & Rapid quantitation of magnetization transfer using pulsed off-resonance irradiation and echo planar imaging. Magn. Reson. Med. 53, 103–109 (2005).

  25. 25.

    , , , & Evaluating the glucose tolerance test in mice. Am. J. Physiol. Endocrinol. Metab. 295, E1323–E1332 (2008).

  26. 26.

    & Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet. Med. 15, 539–553 (1998).

  27. 27.

    et al. Procedure guideline for tumor imaging with 18F-FDG PET/CT 1.0. J. Nucl. Med. 47, 885–895 (2006).

  28. 28.

    , , , & Procedure guideline for general imaging: 1.0. Society of Nuclear Medicine. J. Nucl. Med. 37, 2087–2092 (1996).

  29. 29.

    et al. Whole-body MRI versus PET in assessment of multiple myeloma disease activity. AJR Am. J. Roentgenol. 192, 980–986 (2009).

  30. 30.

    et al. [Cost considerations for whole-body MRI and PET/CT as part of oncologic staging] Radiologe 48, 384–396 (2008).

  31. 31.

    et al. Whole-body dual-modality PET/CT and whole-body MRI for tumor staging in oncology. J. Am. Med. Assoc. 290, 3199–3206 (2003).

  32. 32.

    Molecular Imaging: Radiopharmaceuticals for PET and SPECT (Springer, London, 2009).

  33. 33.

    et al. Guidelines for the welfare and use of animals in cancer research. Br. J. Cancer 102, 1555–1577 (2010).

  34. 34.

    , , , & Extracranial measurements of amide proton transfer using exchange-modulated point-resolved spectroscopy (EXPRESS). NMR Biomed. 25, 829–834 (2012).

  35. 35.

    et al. Cardiac arterial spin labeling using segmented ECG-gated Look-Locker FAIR: variability and repeatability in preclinical studies. Magn. Reson. Med. 69, 238–247 (2013).

  36. 36.

    et al. In vivo quantitative mapping of cardiac perfusion in rats using a noninvasive MR spin-labeling method. J. Magn. Reson. Imaging 8, 1240–1245 (1998).

  37. 37.

    et al. Equilibrium contrast CMR for the detection of amyloidosis in mice. J. Cardiovasc. Magn. Reson. 13 (suppl. 1), 60 (2011).

  38. 38.

    et al. Non-invasive in vivo imaging of vessel calibre in orthotopic prostate tumour xenografts. Int. J. Cancer 130, 1284–1293 (2012).

  39. 39.

    et al. Investigating temporal fluctuations in tumor vasculature with combined carbogen and ultrasmall superparamagnetic iron oxide particle (CUSPIO) imaging. Magn. Reson. Med. 66, 227–234 (2011).

Download references


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.


  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


  1. Search for Simon Walker-Samuel in:

  2. Search for Rajiv Ramasawmy in:

  3. Search for Francisco Torrealdea in:

  4. Search for Marilena Rega in:

  5. Search for Vineeth Rajkumar in:

  6. Search for S Peter Johnson in:

  7. Search for Simon Richardson in:

  8. Search for Miguel Gonçalves in:

  9. Search for Harold G Parkes in:

  10. Search for Erik Årstad in:

  11. Search for David L Thomas in:

  12. Search for R Barbara Pedley in:

  13. Search for Mark F Lythgoe in:

  14. Search for Xavier Golay in:


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.

Supplementary information

PDF files

  1. 1.

    Supplementary Text and Figures

    Supplementary Figures 1–7 and Supplementary Methods

About this article

Publication history





Further reading

Newsletter Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing