Targeted Hsp70 fluorescence molecular endoscopy detects dysplasia in Barrett's esophagus.
Eur J Nucl Med Mol Imaging
; 49(6): 2049-2063, 2022 05.
Article
em En
| MEDLINE
| ID: mdl-34882260
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.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Esôfago de Barrett
/
Neoplasias Esofágicas
/
Adenocarcinoma
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Eur J Nucl Med Mol Imaging
Assunto da revista:
MEDICINA NUCLEAR
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Alemanha