Investigating the genomic landscape of brain tumours using metabolic imaging

Kevin Brindle1

1University of Cambridge, Cambridge, UK


Nuclear spin hyperpolarization can increase sensitivity in the magnetic resonance imaging experiment by >10,000-fold [1].  This has allowed imaging of injected hyperpolarized 13C labelled cell substrates in vivo and, more importantly, their metabolic conversion into other cell metabolites. We have been using this technique both to detect treatment response [2,3] and to investigate the tumour microenvironment [4,5] (reviewed in [6-8]).  The technique has transferred to the clinic recently with a study in prostate cancer [9] and we expect to start patient studies in Cambridge later this year.

In this talk I will discuss recent work in which we have used hyperpolarized [1-13C]pyruvate to investigate glycolytic metabolism in patient derived xenograft (PDX) models of glioblastoma.   These measurements have shown significant heterogeneity between tumours derived from different patients, which we believe is related to underlying oncogenic mutations.

1.         Ardenkjaer-Larsen, J.H., et al. Proc Natl Acad Sci U S A 100, 10158-10163 (2003).

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

3.         Rodrigues, T.B., et al. Nat Med 20, 93-97 (2014).

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

5.         Bohndiek, S.E., et al. J Am Chem Soc 133, 11795-11801 (2011).

6.         Brindle, K.M., et al. Magn Reson Med 66, 505-519 (2011).

7.         Brindle, K. Brit. J. Radiol. 85, 697-708 (2012).

8.         Brindle, K.M. Journal of the American Chemical Society 137, 6418-6427 (2015).

9.         Nelson, S.J., et al. Science Translational Medicine 5, 198ra108 (2013).