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Improved methods for early cancer detection arising from Barrett’s oesophagus (BE) are still needed. Imaging molecular expression patterns in BE patients can target neoplasia. We demonstrate a multiplexed fluorescence imaging approach to detect premalignant lesions with two fluorescently labeled heptapeptides specific for EGFR and ErbB2. Twenty-two BE patients underwent endoscopic imaging with a multimodal scanning fiber endoscope (mmSFE). In this pilot study, 92% of neoplastic lesions could be imaged by comparison with pathology, with only 11% false positives. This first-in-human study demonstrates feasibility to concurrently detect multiple targets in vivo and potential for early detection of cancers that are molecularly heterogeneous.
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Background
Oesophageal adenocarcinoma (EAC) is a deadly disease that has increased dramatically in incidence over the past several decades.1 2 Endoscopic screening with white light illumination and random biopsy is limited by sampling error.3 Dysplasia often presents with flat architecture and patchy distribution.4 EGFR and ErbB2 are transmembrane tyrosine kinase receptors that stimulate epithelial cell growth, proliferation and differentiation.5 Overexpression of these targets reflects a higher risk for cancer progression.6–8 Multiplexed imaging methods take advantage of the broad spectrum of light over the visible and near-infrared (NIR) regimen. We aim to demonstrate clinical feasibility to visualise EGFR and ErbB2 expression simultaneously in vivo to detect Barrett’s neoplasia.
Methods
Consecutive patients referred for either evaluation or therapy of Barrett’s neoplasia were recruited for the study (NCT03589443). An mmSFE was designed to collect multiplexed fluorescence images concurrently. Target/background (T/B) ratios were calculated for each fluorescence image. More details on the methods and the multiplexed imaging technology can be found in the online supplemental file.
Supplemental material
Results
The peptide QRHKPRE specific for EGFR was labelled with Cy5 via a GGGSK linker, (figure 1A).9 KSPNPRF, specific for ErbB2, was labelled with IRDye800 via a GGGSC linker (figure 1B). …
Supplementary materials
Supplementary Data
This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.
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