Imaging tumour metabolism using hyperpolarised 13C magnetic resonance spectroscopy


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Kevin Brindle1
1University of Cambridge, Cambridge, UK

Abstract

Nuclear spin hyperpolarization techniques can increase sensitivity in the MR experiment by >10,000x. This has allowed us to image the location of labelled cell substrates and, more importantly, their metabolic conversion into other metabolites. These substrates include pyruvate [1], glutamine [2], glutamate [3], fumarate [4], bicarbonate [5] and ascorbate [6]. We have shown that exchange of hyperpolarized 13C label between lactate and pyruvate can be imaged in animal models of lymphoma and glioma and that this flux is decreased post-treatment [1,7]. We showed that hyperpolarized [1,4-13C]fumarate can be used to detect tumour cell necrosis post treatment in lymphoma [4] and more recently that the polarized pyruvate and fumarate experiments can detect early evidence of treatment response in a breast tumour model [8] and can detect very early responses to anti-vascular [9] and anti-angiogenic drugs. We have shown that tissue pH can be imaged from the ratio of the signal intensities of hyperpolarized H13CO3- and 13CO2 following intravenous injection of hyperpolarized H13CO3¯ [5] and that tumour redox state can be determined by monitoring the oxidation and reduction of [1-13C]ascorbate and [1-13C]dehydroascorbate respectively [6].

1. Day, S.E., et al. Nature Med 13, 1382-1387 (2007).

2. Gallagher, F., et al. Magn. Reson. Med. 60, 253-257 (2008).

3. Gallagher, F., et al. Magn Reson Med In press(2011).

4. Gallagher, F.A., et al. Proc. Natl Acad. Sci. U.S.A. 106, 19801-19806 (2009).

5. Gallagher, F., et al. Nature 453, 940-943 (2008).

6. Bohndiek, S.E., et al. J Am Chem Soc In press(2011).

7. Day, S.E., et al. Magnetic Resonance in Medicine 65, 557-563 (2011).

8. Witney, T.H., et al. Brit. J. Cancer 103, 1400-1406 (2010).

9. Bohndiek, S.E., et al. Molec. Cancer Ther. 9, 3278-3288 (2010).

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