Imaging sialylated tumor cell glycans in vivo

Neves, A. A., Stöckmann, H., Harmston, R. R., Pryor, H. J., Alam, I. S., Ireland-Zecchini, H., Lewis, D. Y. , Lyons, S. K., Leeper, F. J. and Brindle, K. M. (2011) Imaging sialylated tumor cell glycans in vivo. FASEB Journal, 25(8), pp. 2528-2537. (doi: 10.1096/fj.10-178590) (PMID:21493886)

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Cell surface glycans are involved in numerous physiological processes that involve cell-cell interactions and migration, including lymphocyte trafficking and cancer metastasis. We have used a bioorthogonal metabolic labeling strategy to detect cell surface glycans and demonstrate, for the first time, fluorescence and radionuclide imaging of sialylated glycans in a murine tumor model in vivo. Peracetylated azido-labeled N-acetyl-mannosamine, injected intraperitoneally, was used as the metabolic precursor for the biosynthesis of 5-azidoneuraminic, or azidosialic acid. Azidosialic acid-labeled cell surface glycans were then reacted, by Staudinger ligation, with a biotinylated phosphine injected intraperitoneally, and the biotin was detected by subsequent intravenous injection of a fluorescent or radiolabeled avidin derivative. At 24 h after administration of NeutrAvidin, labeled with either a far-red fluorophore or 111In, there was a significant azido-labeled N-acetyl-mannosamine-dependent increase in tumor-to-tissue contrast, which was detected using optical imaging or single-photon-emission computed tomography (SPECT), respectively. The technique has the potential to translate to the clinic, where, given the prognostic relevance of altered sialic acid expression in cancer, it could be used to monitor disease progression.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Lewis, Dr David
Authors: Neves, A. A., Stöckmann, H., Harmston, R. R., Pryor, H. J., Alam, I. S., Ireland-Zecchini, H., Lewis, D. Y., Lyons, S. K., Leeper, F. J., and Brindle, K. M.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:FASEB Journal
Publisher:Federation of American Society of Experimental Biology
ISSN (Online):1530-6860
Published Online:14 April 2011

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