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Open Access Green as soon as Postprint is submitted to ZB.
Targeting c-MET for endoscopic detection of dysplastic lesions within Barrett's esophagus using EMI-137 fluorescence imaging.
Clin. Cancer Res. 31, 98-109 (2024)
PURPOSE: Esophageal cancer (EC) carries a poor prognosis with 5-year overall survival of less than 20%. Barrett's esophagus (BE) increases the risk of esophageal adenocarcinoma (EAC). The aim of this study was to investigate the ability of EMI-137, a mesenchymal-epithelial transition factor (c-MET)-targeting optical imaging tracer, to detect dysplasia in BE. EXPERIMENTAL DESIGN: c-MET expression in human esophageal tissue was investigated using Gene Expression Omnibus (GEO) datasets, tissue microarrays and BE biopsies. EMI-137 was tested in a dual xenograft mouse model bearing OE33 (c-MET high expression) and FLO-1 (c-MET low expression) tumors. Fluorescence molecular endoscopy (FME) was performed in a mouse model of Barrett's-like metaplasia and dysplasia (L2-IL1β). Tumors and organs-of-interest were evaluated through ex vivo fluorescence imaging. RESULTS: MET mRNA expression analyses and c-MET immunostaining confirmed upregulation of c-MET in BE and EAC compared to normal epithelium. There was strong accumulation of EMI-137 in OE33 xenografts 3 h post injection decreasing by more than 50% on co-injection of a 10-fold molar excess of unlabeled EMI-137. The target-to background ratio (TBR) at 3 h p.i. for OE33 and FLO-1 tumors was 10.08 and 1.42, respectively. FME of L2-IL1β mice showed uptake of EMI-137 in dysplastic lesions within BE with a TBR of 1.9 in vivo, and greater than 2 in ex vivo fluorescence imaging. CONCLUSIONS: EMI-137 accumulates in dysplastic lesions within BE and in c-MET positive EAC. EMI-137 imaging has potential as a screening and surveillance tool for patients with BE and as a means to detecting dysplasia and EAC.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Adenocarcinoma; Identification; Inflammation
ISSN (print) / ISBN
1078-0432
e-ISSN
1557-3265
Journal
Clinical Cancer Research
Quellenangaben
Volume: 31,
Issue: 1,
Pages: 98-109
Publisher
American Association for Cancer Research (AACR)
Publishing Place
615 Chestnut St, 17th Floor, Philadelphia, Pa 19106-4404 Usa
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Biological and Medical Imaging (IBMI)
Grants
Deutsche Forschungsgemeinschaft
Sonderforschungsprojekt Collaborative Research Center Imaging for Selection
Cancer Research UK
MOTI-VATE Graduate School, Faculty of Medicine, University of Freiburg
Medical Affairs Bureau, Ministry of National Defense, Taiwan
Medical Affairs Bureau (MAB)
Sonderforschungsprojekt Collaborative Research Center Imaging for Selection
Cancer Research UK
MOTI-VATE Graduate School, Faculty of Medicine, University of Freiburg
Medical Affairs Bureau, Ministry of National Defense, Taiwan
Medical Affairs Bureau (MAB)