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

Fang HY, Stangl S, Marcazzan S, Carvalho MJB, Baumeister T, Anand A, Strangmann J, Huspenina JS, Wang TC, Schmid RM, Feith M, Friess H, Ntziachristos V, Multhoff G, Gorpas D, Quante M (2022)

Publication Type: Journal article

Publication year: 2022

Journal

European Journal of Nuclear Medicine and Molecular Imaging Springer Verlag (Germany)

Book Volume: 49

Pages Range: 2049-2063

Journal Issue: 6

DOI: 10.1007/s00259-021-05582-y

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.

Involved external institutions

Technische Universität München (TUM) DE Germany (DE) Columbia University US United States (USA) (US)

How to cite

APA:

Fang, H.-Y., Stangl, S., Marcazzan, S., Carvalho, M.J.B., Baumeister, T., Anand, A.,... Quante, M. (2022). Targeted Hsp70 fluorescence molecular endoscopy detects dysplasia in Barrett’s esophagus. European Journal of Nuclear Medicine and Molecular Imaging, 49(6), 2049-2063. https://doi.org/10.1007/s00259-021-05582-y

MLA:

Fang, Hsin-Yu, et al. "Targeted Hsp70 fluorescence molecular endoscopy detects dysplasia in Barrett’s esophagus." European Journal of Nuclear Medicine and Molecular Imaging 49.6 (2022): 2049-2063.

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