About the Project
Patients with similar tumour types can show markedly different responses to the same therapy. The development of new treatments would benefit, therefore, from the introduction of imaging methods that allow an early assessment of treatment response in individual patients, allowing rapid selection of the most effective treatment [1].
We have been developing methods for detecting the early responses of tumours to therapy, including magnetic resonance (MR) imaging of tumour cell metabolism using hyperpolarized 13C-labelled cell metabolites. Nuclear spin hyperpolarization can increase sensitivity in the MR experiment by >10,000x. This has allowed us to image the location of labelled cell substrates in vivo and, more importantly, their metabolic conversion into other metabolites.
More recently we have shown that we can follow, using hyperpolarized [1-13C]pyruvate, the progression of pancreatic precursor lesions, in a genetically engineered mouse model of the disease, which potentially could be used clinically to guide earlier intervention [15]. In this project the student will use imaging with hyperpolarized [1-13C]pyruvate to detect response of pancreatic tumours in this mouse model to novel therapies targeted at the PI3K pathway.
Depending on the outcome of these experiments we anticipate translating this work to the clinic. In 2016 we conducted our first study in a patient using this technique (the first outside North America) (http://www.cambridge-tv.co.uk/professor-kevin-brindle-and-dr-ferdia-gallagher-cancer-scanning/) and the plan is to conduct further studies in pancreatic cancer patients.
The student will learn a variety of techniques, including magnetic resonance imaging and spectroscopy; metabolic biochemistry, particularly as it relates to oncology and tumour cell and molecular biology.
References
1. Brindle, K., Nature Rev Cancer, 8, 94-107 (2008)
2. Day, S.E., et al., Nature Med, 13, 1382-1387 (2007)
3. Kennedy, B.W.C., et al., J Am Chem Soc, 134, 4969−4977 (2012)
4. Gallagher, F., et al., Magn. Reson. Med., 60, 253-257 (2008)
5. Gallagher, F., et al., Magn Reson Med, 66, 18-23 (2011)
6. Gallagher, F.A., et al., Proc Natl Acad Sci U S A, 106, 19801-19806 (2009)
7. Gallagher, F., et al., Nature, 453, 940-943 (2008)
8. Bohndiek, S.E., et al., J Am Chem Soc, 133, 11795-11801 (2011)
9. Rodrigues, T.B., et al., Nat Med, 20, 93-97 (2014)
10. Brindle, K.M., J. Amer. Chem. Soc., 137, 6418-6427 (2015)
11. Day, S.E., et al., Magn Reson Med, 65, 557-563 (2011)
12. Witney, T.H., et al., Brit. J. Cancer, 103, 1400-1406 (2010)
13. Bohndiek, S.E., et al., Molecular Cancer Therapeutics, 9, 3278-3288 (2010)
14. Bohndiek, S.E., et al., Cancer Research, 72, 854-864 (2012)
15. Serrao, E.M., et al., Gut, 65, 465–475 (2016)
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