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Multimodal endoscope can quantify wide-field fluorescence detection of Barrett's neoplasia.

ABSTRACT: To demonstrate the clinical use of a multimodal endoscope with a targeted fluorescently labeled peptide for quantitative detection of Barrett's neoplasia.We studied 50 patients with Barrett's esophagus using a prototype multimodal endoscope with a fluorescently labeled peptide. Co-registered fluorescence and reflectance images were converted to ratios to correct for differences in distance and geometry over the image field of view. The ratio images were segmented using a unique threshold that maximized the variance between high and low intensities to localize regions of high grade dysplasia (HGD) and esophageal adenocarcinoma (EAC).Early neoplasia (HGD and EAC) was identified with 94?% specificity and 96?% positive predictive value at a threshold of 1.49.?The mean results for HGD and EAC were significantly greater than those for squamous/Barrett's esophagus and low grade dysplasia by one-way analysis of variance (ANOVA). The receiver operator characteristic curve for detection of early neoplasia had an area under the curve of 0.884.?No adverse events associated with the endoscope or peptide were found.A multimodal endoscope can quantify fluorescence images from targeted peptides to localize early Barrett's neoplasia. (ClinicalTrials.gov number NCT01630798.).

SUBMITTER: Joshi BP

PROVIDER: S-EPMC5011967 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Multimodal endoscope can quantify wide-field fluorescence detection of Barrett's neoplasia.

Joshi Bishnu P BP Duan Xiyu X Kwon Richard S RS Piraka Cyrus C Elmunzer B Joseph BJ Lu Shaoying S Rabinsky Emily F EF Beer David G DG Appelman Henry D HD Owens Scott R SR Kuick Rork R Doguchi Nobuyuki N Turgeon D Kim DK Wang Thomas D TD

Endoscopy 20151001 2

<h4>Background and study aims</h4>To demonstrate the clinical use of a multimodal endoscope with a targeted fluorescently labeled peptide for quantitative detection of Barrett's neoplasia.<h4>Patients and methods</h4>We studied 50 patients with Barrett's esophagus using a prototype multimodal endoscope with a fluorescently labeled peptide. Co-registered fluorescence and reflectance images were converted to ratios to correct for differences in distance and geometry over the image field of view. T ...[more]

PMID: 26426999

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Project description:Background & aimsMany cancers in the proximal colon develop via from sessile serrated adenomas (SSAs), which have flat, subtle features that are difficult to detect with conventional white-light colonoscopy. Many SSA cells have the V600E mutation in BRAF. We investigated whether this feature could be used with imaging methods to detect SSAs in patients.MethodsWe used phage display to identify a peptide that binds specifically to SSAs, using subtractive hybridization with HT29 colorectal cancer cells containing the V600E mutation in BRAF and Hs738.St/Int cells as a control. Binding of fluorescently labeled peptide to colorectal cancer cells was evaluated with confocal fluorescence microscopy. Rats received intra-colonic 0.0086 mg/kg, 0.026 mg/kg, or 0.86 mg/kg peptide or vehicle and morbidity, mortality, and injury were monitored twice daily to assess toxicity. In the clinical safety study, fluorescently labeled peptide was topically administered, using a spray catheter, to the proximal colon of 25 subjects undergoing routine outpatient colonoscopies (3 subjects were given 2.25 μmol/L and 22 patients were given 76.4 μmol/L). We performed blood cell count, chemistry, liver function, and urine analyses approximately 24 hours after peptide administration. In the clinical imaging study, 38 subjects undergoing routine outpatient colonoscopies, at high risk for colorectal cancer, or with a suspected unresected proximal colonic polyp, were first evaluated by white-light endoscopy to identify suspicious regions. The fluorescently labeled peptide (76.4 μmol/L) was administered topically to proximal colon, unbound peptide was washed away, and white-light, reflectance, and fluorescence videos were recorded digitally. Fluorescence intensities of SSAs were compared with those of normal colonic mucosa. Endoscopists resected identified lesions, which were analyzed histologically by gastrointestinal pathologists (reference standard). We also analyzed the ability of the peptide to identify SSAs vs adenomas, hyperplastic polyps, and normal colonic mucosa in specimens obtained from the tissue bank at the University of Michigan.ResultsWe identified the peptide sequence KCCFPAQ and measured an apparent dissociation constant of Kd = 72 nM and an apparent association time constant of K = 0.174 min-1 (5.76 minutes). During fluorescence imaging of patients during endoscopy, regions of SSA had 2.43-fold higher mean fluorescence intensity than that for normal colonic mucosa. Fluorescence labeling distinguished SSAs from normal colonic mucosa with 89% sensitivity and 92% specificity. The peptide had no observed toxic effects in animals or patients. In the analysis of ex vivo specimens, peptide bound to SSAs had significantly higher mean fluorescence intensity than to hyperplastic polyps.ConclusionsWe have identified a fluorescently labeled peptide that has no observed toxic effects in animals or humans and can be used for wide-field imaging of lesions in the proximal colon. It distinguishes SSAs from normal colonic mucosa with 89% sensitivity and 92% specificity. This targeted imaging method might be used in early detection of premalignant serrated lesions during routine colonoscopies. ClinicalTrials.gov ID: NCT02156557.

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Multimodal endoscope can quantify wide-field fluorescence detection of Barrett's neoplasia.

Publications

Multimodal endoscope can quantify wide-field fluorescence detection of Barrett's neoplasia.

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