234 Visualization of Esophageal Adenocarcinoma With VEGF-Targeted Near-Infrared Fluorescent Molecular Endoscopy

Background: Esophageal adenocarinoma (EAC) is a pressing clinical problem, as it has one of the fastest rising cancer incidence rates worldwide.Barrett Esophagus (BE), a metaplastic change of the normal epithelial lining, is a known precursor for the formation of EAC.The current surveillance approach, random four-quadrant biopsies along the complete BE segment, is controversial and often considered insufficient.By incorporating molecular imaging, a valuable complementary technique in surveillance endoscopy might arise.Methods: First of all, via immunohistochemistry, we evaluated whether vascular endothelial growth factor (VEGF-A) could serve as a discriminating target in the esophagus.Secondly, we performed a pilot intervention study to investigate the use of VEGF-targeted Nearinfrared Molecular Fluorescence Endoscopy (NIR-MFE) in early EAC diagnostics.In total, ten patients with established dysplasia and/or superficial EAC (pT1), scheduled for endoscopic mucosal resection (EMR), were included: five patients received the fluorescently labeled anti-VEGF monoclonal antibody topically (bevacizumab-800CW; 100 µg/ml) and five patients received a microdose of this same tracer intravenously, two days prior to the procedure (4.5 mg).The presence of fluorescent signals was evaluated in real-time, directly prior to the EMR, using a custom-made fiber-based NIR-MFE system.To objectify and semi-quantify the fluorescent signals ex vivo, we performed macroscopic (800nm flatbed scanning) and microscopic fluorescence signal analyses on the esophageal specimen.Results: Firstly, we observed high VEGF-A expression in dysplastic (85%) and EAC (81%) samples, compared to an overall low protein expression in normal epithelial linings (incl.BE), therefore validating VEGF-A as a discriminating target.In addition, our VEGF-targeted NIR-MFE approach demonstrated real-time identification of early EAC lesions (3/5 for intravenous group; 5/5 for topical group).Based on these preliminary in vivo results, flat and difficult to distinguish EAC lesions were identifiable with NIR-MFI, especially following topical tracer administration.In addition, we were able to detect two novel dysplastic areas, which were not identified with high-definition endoscopic inspection alone.Ex vivo fluorescence-signal analyses revealed increased uptake of the tracer in EAC and dysplasia compared to normal epithelial linings.Conclusion: We are the first to demonstrate that VEGF-guided NIR-MFE, following local or systemic tracer administration, is able to detect early esophageal cancer lesions.Although our study illustrates the potential of endoscopic wide-field molecular imaging, further research is required to proof the additive role of NIR-MFE in future BE surveillance strategies.