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European Journal of Nuclear Medicine and Molecular Imaging
Published in: European Journal of Nuclear Medicine and Molecular Imaging 6/2022

Open Access 01-05-2022 | Endoscopy | Original Article

Targeted Hsp70 fluorescence molecular endoscopy detects dysplasia in Barrett’s esophagus

Authors: Hsin-Yu Fang, Stefan Stangl, Sabrina Marcazzan, Marcos J. Braz Carvalho , Theresa Baumeister, Akanksha Anand, Julia Strangmann, Julia Slotta Huspenina, Timothy C. Wang, Roland M. Schmid, Marcus Feith, Helmut Friess, Vasilis Ntziachristos, Gabriele Multhoff, Dimitris Gorpas, Michael Quante

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 6/2022

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Abstract

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.
Appendix
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Metadata
Title
Targeted Hsp70 fluorescence molecular endoscopy detects dysplasia in Barrett’s esophagus
Authors
Hsin-Yu Fang
Stefan Stangl
Sabrina Marcazzan
Marcos J. Braz Carvalho
Theresa Baumeister
Akanksha Anand
Julia Strangmann
Julia Slotta Huspenina
Timothy C. Wang
Roland M. Schmid
Marcus Feith
Helmut Friess
Vasilis Ntziachristos
Gabriele Multhoff
Dimitris Gorpas
Michael Quante
Publication date
01-05-2022
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 6/2022
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-021-05582-y

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