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Professor Kevin Brindle

Research Interests

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 for a specific patient (Brindle, Nat. Rev. Cancer 2008; 8: 1).

We have been developing novel and potentially clinically applicable imaging methods for detecting the early responses of tumours to treatment.  This has included a targeted imaging agent for detecting tumour cell death, which has been patented and which we are planning to take to the clinic, and a new magnetic resonance method for imaging tumour cell metabolism.

Through a partnership with GE Healthcare we have developed nuclear spin hyperpolarization as a novel tool for imaging tissue metabolism in vivo. Nuclear spin polarization offers enormous gains in sensitivity, as much as 10,000 – 100,000x, which makes it possible not only to image the distribution of isotopically-labelled cellular metabolites in vivo, but also their enzymatic transformation into other species. This has provided us with more sensitive ways to detect tumour responses to treatment and, with some substrates, is giving new insights into tumour metabolism in vivo.  We now have funding for a clinical trial of this technique for assessing treatment response in glioma, lymphoma and breast cancer patients, which is due to start in 2014.  This will be only the second trial worldwide and the first in Europe.

Key Publications

Rodrigues, T. B., Serrao, E. M., Kennedy, B. W. C., Hu, D., Kettunen, M. I. and Brindle, K. M. Magnetic resonance imaging of tumor glycolysis using hyperpolarized 13C labeled glucose. Nature Med 2013 In press.
 
Roberts EW, Deonarine A, Jones JO, Denton AE, Feig C, Lyons SK, Espeli M, Kraman M, McKenna B, Wells RJ, Zhao Q, Caballero OL, Larder R, Coll AP, O'Rahilly S, Brindle KM, Teichmann SA, Tuveson DA, Fearon DT.  J Exp Med. 2013 May 27. [Epub ahead of print] Depletion of stromal cells expressing fibroblast activation protein-α from skeletal muscle and bone marrow results in cachexia and anemia.
 
Bohndiek, S. E., Kettunen, M. I., Hu, D., Kennedy, B. W. C., Boren, J., Gallagher, F. A., Brindle, K. M. Hyperpolarized [1-13C]-ascorbic and dehydroascorbic acid: Vitamin C as a probe for imaging redox status in vivoJ. Amer. Chem. Soc. 2011 133, 11795-11801.
Production of hyperpolarized [1,4-13C2]malate from [1,4-13C2]fumarate is a marker of cell necrosis and treatment response in tumors. Gallagher, F.A., Kettunen, M. I., Hu, D.-E., Jensen, R. J., in ‘t Zandt, R., Karlsson, M., Gisselsson, A., Nelson, S. K., Witney, T. H., Bohndiek, S. E., Hansson, G., Peitersen, T., Lerche, M. H., Brindle, K. M.  Proc. Natl Acad. Sci. USA 2009106, 19801-19806.

Gallagher, F. A., Kettunen, M. I., Day, S. E., Hu, D.-E., Ardenkjær-Larsen, J. H., in ‘t Zandt, R., Jensen, P. R., Karlsson, M., Golman, K., Lerche, M. H., and Brindle, K. M. Magnetic resonance imaging of pH in vivo using hyperpolarized 13C-labeled bicarbonate. 2008 Nature 453, 940-943.

Krishnan, A.S., Neves, A. A., de Backer, M. M., Hu, D.-E., Davletov, B., Kettunen, M. I., and Brindle, K. M.  Detection of cell death in tumors using MRI and a gadolinium-based targeted contrast agent. Radiology 2008 246, 854-862.