Details der Publikation - Targeted Hsp70 fluorescence molecular endoscopy detects dysplasia in Barrett’s esophagus

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

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..

Medienart:	E-Artikel

Erscheinungsjahr:	2021
Erschienen:	2021

Enthalten in:	Zur Gesamtaufnahme - volume:49
Enthalten in:	European journal of nuclear medicine and molecular imaging - 49(2021), 6 vom: 09. Dez., Seite 2049-2063

Sprache:	Englisch

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

Links:	Volltext [kostenfrei]

Themen:	Barrett esophagus Esophageal adenocarcinoma Fluorescence molecular endoscopy Hsp70 Surveillance strategies

Anmerkungen:	© The Author(s) 2021

doi:	10.1007/s00259-021-05582-y

funding:
Förderinstitution / Projekttitel:

PPN (Katalog-ID):	OLC2130181813

Internformat


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520			\|a 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.
650		4	\|a Barrett esophagus
650		4	\|a Hsp70
650		4	\|a Fluorescence molecular endoscopy
650		4	\|a Esophageal adenocarcinoma
650		4	\|a Surveillance strategies
700	1		\|a Stangl, Stefan \|4 aut
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Targeted Hsp70 fluorescence molecular endoscopy detects dysplasia in Barrett’s esophagus

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