Development of novel imaging methods in mouse cancer models


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Kevin Brindle1

1University of Cambridge, Cambridge, UK

Abstract

Patients with similar tumour types can have 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 using mouse models to develop novel imaging methods for detecting the early responses of tumours to therapy that could subsequently be translated to the clinic. This has included a targeted MRI contrast agent for detecting tumour cell death [2-4] and MR imaging of tumour cell metabolism using hyperpolarized 13C-labelled cellular metabolites [5-8]. We have also been developing novel methods for imaging cell surface glycans as a way of detecting early dysplasia, tumour progression and treatment response. This has included a bio-orthogonal metabolic labelling approach in which animals are injected with an azido-labelled metabolic precursor of sialic acid, which is then detected in vivo by Staudinger ligation with a biotinylated phosphine (bPP) and subsequent injection of a fluorescently or radiolabelled avidin, for optical or radionuclide imaging (SPECT) respectively [9,10]. 1. Brindle, K. Nature Rev. Cancer 8, 1-14 (2008). 2. Zhao, M., et al. Nat. Med. 7, 1241-1244 (2001). 3. Krishnan, A.S., et al. Radiology 246, 854-862 (2008). 4. Alam, I.S., et al. Bioconjug Chem 21, 884-891 (2010). 5. Day, S.E., et al. Nature Med 13, 1382-1387 (2007). 6. Gallagher, F., et al. Nature 453, 940-943 (2008). 7. Gallagher, F.A., et al. Proc. Natl Acad. Sci. U.S.A. 106, 19801-19806 (2009). 8. Bohndiek, S.E., et al. J Am Chem Soc In press(2011). 9. Stockmann, H., et al. Chem. Sci. 2, 932-936 (2011). 10. Neves, A.A., et al. Faseb J In press(2011).

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