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Fang, H.Y.* ; Stangl, S.* ; Marcazzan, S. ; Carvalho, M.J.B.* ; Baumeister, T.* ; Anand, A.* ; Strangmann, J.* ; Huspenina, J.S.* ; Wang, T.C.* ; Schmid, R.M.* ; Feith, M.* ; Friess, H.* ; Ntziachristos, V. ; Multhoff, G.* ; Gorpas, D. ; Quante, M.*

Targeted Hsp70 fluorescence molecular endoscopy detects dysplasia in Barrett's esophagus.

Eur. J. Nucl. Med. Mol. Imaging, DOI: 10.1007/s00259-021-05582-y (2021)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
PURPOSE: The incidence of esophageal adenocarcinoma (EAC) has been increasing for decades without significant improvements in treatment. Barrett's esophagus (BE) is best established risk factor for EAC, but current surveillance with random biopsies cannot predict progression to cancer in most BE patients due to the low sensitivity and specificity of high-definition white light endoscopy. METHODS: Here, we evaluated the membrane-bound highly specific Hsp70-specific contrast agent Tumor-Penetrating Peptide (Hsp70-TPP) in guided fluorescence molecular endoscopy biopsy. RESULTS: Hsp70 was significantly overexpressed as determined by IHC in dysplasia and EAC compared with non-dysplastic BE in patient samples (n = 12) and in high-grade dysplastic lesions in a transgenic (L2-IL1b) mouse model of BE. In time-lapse microscopy, Hsp70-TPP was rapidly taken up and internalized  by human BE dysplastic patient-derived organoids. Flexible fluorescence endoscopy of the BE mouse model allowed a specific detection of Hsp70-TPP-Cy5.5 that corresponded closely with the degree of dysplasia but not BE. Ex vivo application of Hsp70-TPP-Cy5.5 to freshly resected whole human EAC specimens revealed a high (> 4) tumor-to-background ratio and a specific detection of previously undetected tumor infiltrations. CONCLUSION: In summary, these findings suggest that Hsp70-targeted imaging using fluorescently labeled TPP peptide may improve tumor surveillance in BE patients.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Barrett Esophagus ; Esophageal Adenocarcinoma ; Fluorescence Molecular Endoscopy ; Hsp70  ; Surveillance Strategies; Heat-shock Proteins; Plasma-membrane Expression; Heat-shock-protein-70 Hsp70; Tumor-cells; Mouse Model; Adenocarcinoma; Surface; Risk
ISSN (print) / ISBN 1619-7070
e-ISSN 1432-105X
Journal European Journal of Nuclear Medicine and Molecular Imaging
Publisher Springer
Publishing Place One New York Plaza, Suite 4600, New York, Ny, United States
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Biological and Medical Imaging (IBMI)
Grants Deutsche Forschungsgemeinschaft