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Detection of Barrett’s neoplasia with a near-infrared fluorescent heterodimeric peptide
Background Esophageal adenocarcinoma (EAC) is a molecularly heterogeneous disease with poor prognosis that is rising rapidly in incidence. We aimed to demonstrate specific binding by a peptide heterodimer to Barrett’s neoplasia in human subjects. Methods Peptide monomers specific for EGFR and ErbB2...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Georg Thieme Verlag KG
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9718637/ https://www.ncbi.nlm.nih.gov/pubmed/35299273 http://dx.doi.org/10.1055/a-1801-2406 |
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author | Chen, Jing Jiang, Yang Chang, Tse-Shao Rubenstein, Joel H. Kwon, Richard S. Wamsteker, Erik J. Prabhu, Anoop Zhao, Lili Appelman, Henry D. Owens, Scott R. Beer, David G. Turgeon, D. Kim Seibel, Eric J. Wang, Thomas D. |
author_facet | Chen, Jing Jiang, Yang Chang, Tse-Shao Rubenstein, Joel H. Kwon, Richard S. Wamsteker, Erik J. Prabhu, Anoop Zhao, Lili Appelman, Henry D. Owens, Scott R. Beer, David G. Turgeon, D. Kim Seibel, Eric J. Wang, Thomas D. |
author_sort | Chen, Jing |
collection | PubMed |
description | Background Esophageal adenocarcinoma (EAC) is a molecularly heterogeneous disease with poor prognosis that is rising rapidly in incidence. We aimed to demonstrate specific binding by a peptide heterodimer to Barrett’s neoplasia in human subjects. Methods Peptide monomers specific for EGFR and ErbB2 were arranged in a heterodimer configuration and labeled with IRDye800. This near-infrared (NIR) contrast agent was topically administered to patients with Barrett’s esophagus (BE) undergoing either endoscopic therapy or surveillance. Fluorescence images were collected using a flexible fiber accessory passed through the instrument channel of an upper gastrointestinal endoscope. Fluorescence images were collected from 31 BE patients. A deep learning model was used to segment the target (T) and background (B) regions. Results The mean target-to-background (T/B) ratio was significantly greater for high grade dysplasia (HGD) and EAC versus BE, low grade dysplasia (LGD), and squamous epithelium. At a T/B ratio of 1.5, sensitivity and specificity of 94.1 % and 92.6 %, respectively, were achieved for the detection of Barrett’s neoplasia with an area under the curve of 0.95. No adverse events attributed to the heterodimer were found. EGFR and ErbB2 expression were validated in the resected specimens. Conclusions This “first-in-human” clinical study demonstrates the feasibility of detection of early Barrett’s neoplasia using a NIR-labeled peptide heterodimer. |
format | Online Article Text |
id | pubmed-9718637 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Georg Thieme Verlag KG |
record_format | MEDLINE/PubMed |
spelling | pubmed-97186372022-12-03 Detection of Barrett’s neoplasia with a near-infrared fluorescent heterodimeric peptide Chen, Jing Jiang, Yang Chang, Tse-Shao Rubenstein, Joel H. Kwon, Richard S. Wamsteker, Erik J. Prabhu, Anoop Zhao, Lili Appelman, Henry D. Owens, Scott R. Beer, David G. Turgeon, D. Kim Seibel, Eric J. Wang, Thomas D. Endoscopy Background Esophageal adenocarcinoma (EAC) is a molecularly heterogeneous disease with poor prognosis that is rising rapidly in incidence. We aimed to demonstrate specific binding by a peptide heterodimer to Barrett’s neoplasia in human subjects. Methods Peptide monomers specific for EGFR and ErbB2 were arranged in a heterodimer configuration and labeled with IRDye800. This near-infrared (NIR) contrast agent was topically administered to patients with Barrett’s esophagus (BE) undergoing either endoscopic therapy or surveillance. Fluorescence images were collected using a flexible fiber accessory passed through the instrument channel of an upper gastrointestinal endoscope. Fluorescence images were collected from 31 BE patients. A deep learning model was used to segment the target (T) and background (B) regions. Results The mean target-to-background (T/B) ratio was significantly greater for high grade dysplasia (HGD) and EAC versus BE, low grade dysplasia (LGD), and squamous epithelium. At a T/B ratio of 1.5, sensitivity and specificity of 94.1 % and 92.6 %, respectively, were achieved for the detection of Barrett’s neoplasia with an area under the curve of 0.95. No adverse events attributed to the heterodimer were found. EGFR and ErbB2 expression were validated in the resected specimens. Conclusions This “first-in-human” clinical study demonstrates the feasibility of detection of early Barrett’s neoplasia using a NIR-labeled peptide heterodimer. Georg Thieme Verlag KG 2022-06-20 /pmc/articles/PMC9718637/ /pubmed/35299273 http://dx.doi.org/10.1055/a-1801-2406 Text en The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License, which permits unrestricted reproduction and distribution, for non-commercial purposes only; and use and reproduction, but not distribution, of adapted material for non-commercial purposes only, provided the original work is properly cited. |
spellingShingle | Chen, Jing Jiang, Yang Chang, Tse-Shao Rubenstein, Joel H. Kwon, Richard S. Wamsteker, Erik J. Prabhu, Anoop Zhao, Lili Appelman, Henry D. Owens, Scott R. Beer, David G. Turgeon, D. Kim Seibel, Eric J. Wang, Thomas D. Detection of Barrett’s neoplasia with a near-infrared fluorescent heterodimeric peptide |
title | Detection of Barrett’s neoplasia with a near-infrared fluorescent heterodimeric peptide |
title_full | Detection of Barrett’s neoplasia with a near-infrared fluorescent heterodimeric peptide |
title_fullStr | Detection of Barrett’s neoplasia with a near-infrared fluorescent heterodimeric peptide |
title_full_unstemmed | Detection of Barrett’s neoplasia with a near-infrared fluorescent heterodimeric peptide |
title_short | Detection of Barrett’s neoplasia with a near-infrared fluorescent heterodimeric peptide |
title_sort | detection of barrett’s neoplasia with a near-infrared fluorescent heterodimeric peptide |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9718637/ https://www.ncbi.nlm.nih.gov/pubmed/35299273 http://dx.doi.org/10.1055/a-1801-2406 |
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