Detection of early esophageal neoplastic Barrett lesions with quantified fluorescence molecular endoscopy using cetuximab-800CW

Abstract

Esophageal adenocarcinoma (EAC) causes 6 % of cancer-related deaths worldwide. Near-infrared fluorescence molecular endoscopy (NIR-FME) uses a tracer that targets overexpressed proteins. In this study we aim to investigate the feasibility of an epidermal growth factor receptor (EGFR) targeted tracer, cetuximab-800CW, to improve detection of early-stage EAC. Methods: We validated EGFR expression in 73 esophageal tissue sections. Subsequently, we topically administered cetuximab-800CW and performed high-definition white-light endoscopy (HD-WLE), narrow band imaging (NBI) and NIR-FME in fifteen patients with Barrett’s esophagus (BE). Intrinsic fluorescence values were quantified using multi-diameter single fiber reflectance (MDSFR) and single-fiber fluorescence (SFF) spectroscopy. Back-table imaging, histopathological examination and EGFR immunohistochemistry on biopsies collected during NIR-FME procedures were performed and compared to in vivo imaging results. Results: Immunohistochemical pre-analysis showed high EGFR expression in 67% of dysplastic tissue sections. NIR-FME visualized all 12 HD-WLE visible lesions and 5 HD-WLE invisible dysplastic lesions, with increased fluorescence signal in visible dysplastic BE lesions compared to non-dysplastic BE as shown by MDSFR/SFF, reflecting a target-to-background ratio (TBR) of 1.5. Invisible dysplastic lesions also showed increased fluorescence with a TBR of 1.67. Immunohistochemistry analysis showed EGFR overexpression in 16 out of 17 (94%) dysplastic BE lesions, which all showed fluorescence signal. Conclusion: This study has shown that NIR-FME using cetuximab-800CW can improve detection of dysplastic lesions missed by HD-WLE and NBI.