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C-Met targeted fluorescence molecular endoscopy in Barrett's esophagus patients and identification of outcome parameters for phase-I studies.

ABSTRACT: Fluorescence molecular endoscopy (FME) is an emerging technique in the field of gastroenterology that holds potential to improve diagnosis and guide therapy, by serving as a 'red-flag' endoscopic imaging technique. Here, we investigated the safety, feasibility and optimal method of administration of EMI-137, targeting c-Met, during FME in Barrett's Esophagus (BE) and report several outcome parameters for early phase FME studies. Methods: FME was performed in 15 Barrett's neoplasia patients. EMI-137 was administered to three cohorts of five patients: 0.13 mg/kg intravenously (IV); 0.09 mg/kg IV or topically at a dose of 200 ?g/cm BE (n=1) or 100 ?g/cm BE (n=4). Fluorescence was visualized in vivo, quantified in vivo using multi-diameter single-fiber reflectance, single-fiber fluorescence (MDSFR/SFF) spectroscopy and correlated to histopathology and immunohistochemistry. EMI-137 localization was assessed using fluorescence microscopy. Results: FME using different IV and topical doses of EMI-137 appeared to be safe and correctly identified 16/18 lesions, although modest target-to-background ratios were observed (median range of 1.12-1.50). C-Met overexpression varied between lesions, while physiological expression in the stomach-type epithelium was observed. Microscopically, EMI-137 accumulated around the neoplastic cell membranes. We identified several outcome parameters important for the validation of EMI-137 for FME: 1) the optimal administration route; 2) optimal dose and safety; 3) in vivo FME contrast; 4) quantification of intrinsic fluorescence; 5) ex vivo correlation of fluorescence, histopathology and target expression; and 6) microscopic tracer distribution. Conclusions: C-Met targeted FME using EMI-137 may not be the ideal combination to improve BE surveillance endoscopies, however the identified outcome parameters may serve as a valuable guidance for designing and performing future early phase clinical FME studies, independent of which fluorescent tracer is investigated.

SUBMITTER: de Jongh SJ

PROVIDER: S-EPMC7196285 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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C-Met targeted fluorescence molecular endoscopy in Barrett's esophagus patients and identification of outcome parameters for phase-I studies.

de Jongh Steven J SJ Voskuil Floris J FJ Schmidt Iris I Karrenbeld Arend A Kats-Ugurlu Gursah G Meersma Gert Jan GJ Westerhof Jessie J Witjes Max J H MJH van Dam Gooitzen M GM Robinson Dominic J DJ Nagengast Wouter B WB

Theranostics 20200406 12

Fluorescence molecular endoscopy (FME) is an emerging technique in the field of gastroenterology that holds potential to improve diagnosis and guide therapy, by serving as a 'red-flag' endoscopic imaging technique. Here, we investigated the safety, feasibility and optimal method of administration of EMI-137, targeting c-Met, during FME in Barrett's Esophagus (BE) and report several outcome parameters for early phase FME studies. <b>Methods</b>: FME was performed in 15 Barrett's neoplasia patient ...[more]

PMID: 32373217

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Project description:Early detection of esophageal neoplasia enables curative endoscopic therapy, but the current diagnostic standard of care has low sensitivity because early neoplasia is often inconspicuous with conventional white-light endoscopy. Here, we hypothesized that spectral endoscopy could enhance contrast for neoplasia in surveillance of patients with Barrett's esophagus. A custom spectral endoscope was deployed in a pilot clinical study of 20 patients to capture 715 in vivo tissue spectra matched with gold standard diagnosis from histopathology. Spectral endoscopy was sensitive to changes in neovascularization during the progression of disease; both non-dysplastic and neoplastic Barrett's esophagus showed higher blood volume relative to healthy squamous tissue (P = 0.001 and 0.02, respectively), and vessel radius appeared larger in neoplasia relative to non-dysplastic Barrett's esophagus (P = 0.06). We further developed a deep learning algorithm capable of classifying spectra of neoplasia versus non-dysplastic Barrett's esophagus with high accuracy (84.8% accuracy, 83.7% sensitivity, 85.5% specificity, 78.3% positive predictive value, and 89.4% negative predictive value). Exploiting the newly acquired library of labeled spectra to model custom color filter sets identified a potential 12-fold enhancement in contrast between neoplasia and non-dysplastic Barrett's esophagus using application-specific color filters compared with standard-of-care white-light imaging (perceptible color difference = 32.4 and 2.7, respectively). This work demonstrates the potential of endoscopic spectral imaging to extract vascular properties in Barrett's esophagus, to classify disease stages using deep learning, and to enable high-contrast endoscopy. SIGNIFICANCE: The results of this pilot first-in-human clinical trial demonstrate the potential of spectral endoscopy to reveal disease-associated vascular changes and to provide high-contrast delineation of neoplasia in the esophagus. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/81/12/3415/F1.large.jpg.

Dataset Information

C-Met targeted fluorescence molecular endoscopy in Barrett's esophagus patients and identification of outcome parameters for phase-I studies.

Publications

C-Met targeted fluorescence molecular endoscopy in Barrett's esophagus patients and identification of outcome parameters for phase-I studies.

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