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Molecular imaging using fluorescent lectins permits rapid endoscopic identification of dysplasia in Barrett's esophagus

Abstract

Barrett's esophagus is an example of a pre-invasive state, for which current endoscopic surveillance methods to detect dysplasia are time consuming and inadequate. The prognosis of cancer arising in Barrett's esophagus is improved by early detection at the stage of mucosal carcinoma or high-grade dysplasia. Molecular imaging methods could revolutionize the detection of dysplasia, provided they permit a wide field of view and highlight abnormalities in real time. We show here that cell-surface glycans are altered in the progression from Barrett's esophagus to adenocarcinoma and lead to specific changes in lectin binding patterns. We chose wheat germ agglutinin as a candidate lectin with clinical potential. The binding of wheat germ agglutinin to human tissue was determined to be specific, and we validated this specific binding by successful endoscopic visualization of high-grade dysplastic lesions, which were not detectable by conventional endoscopy, with a high signal-to-background ratio of over 5.

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Figure 1: Array data.
Figure 2: Fluorescent lectin histochemistry validation (cohort of n = 80 biopsies).
Figure 3: Representative whole-biopsy fluorescence.
Figure 4: Whole-organ imaging ex vivo.

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Acknowledgements

This work was supported by a research fellowship from GlaxoSmithKline awarded to E.L.B.-L. The authors thank J. Ong, C. Peters, S. Hilborne, E. Moore, N. Shannon, B. Spencer, R. Cayado-Lopez, B. Haynes, J. Gray, W. Howat, J. Harris and S. Reichelt for their advice and support and the Moritex Corporation for lending the evanescent lectin array equipment (Glycostation). This work was supported by a Medical Research Centre core grant (R.C.F.), the Cambridge Experimental Medicine Centre (R.C.F.), the National Institute for Health Research Cambridge Biomedical Research Centre (R.C.F.), a Cancer Research UK core grant (K.M.B.) and a Clinical Research Fellowship from GlaxoSmithKline (E.L.B.-L.). The work undertaken in the Department of Chemistry, University of New York was supported by a New York University startup fund and by the US National Institutes of Health (W.S.E. and L.K.M.). The work undertaken at UCLH/UCL was supported in part by funding from the Department of Health's NIHR Biomedical Research Centre's funding scheme and also by a grant from Cancer Research UK to the Experimental Cancer Research Centre, UCL. The views expressed in this publication are those of the authors and not necessarily those of the UK Department of Health.

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E.L.B.-L. performed the experimental work and data analysis with help from A.A.N., P.L.-S. and L.K.M. M.O. and M.N. performed histopathological analyses. L.K.M. and W.S.E. applied prepared samples for the ratiometric array, and L.B.L. provided samples. R.C.F. and K.M.B. conceived of and supervised this work. The manuscript was written by E.L.B.-L. and R.C.F.

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Correspondence to Rebecca C Fitzgerald.

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The authors declare no competing financial interests.

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Bird-Lieberman, E., Neves, A., Lao-Sirieix, P. et al. Molecular imaging using fluorescent lectins permits rapid endoscopic identification of dysplasia in Barrett's esophagus. Nat Med 18, 315–321 (2012). https://doi.org/10.1038/nm.2616

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