Enhancing early detection of esophageal neoplastic lesions: oral administration of bevacizumab-800CW and cetuximab-800CW for quantified fluorescence molecular endoscopy

Aims Patients with Barrett’s esophagus (BE) have an increased risk of developing esophageal adenocarcinoma (EAC). However, 24% of lesions are missed with surveillance endoscopy. Quantitative fluorescence molecular endoscopy (qFME) with topical fluorescent tracers enabled the BE endoscopist to detect 27%-42% more dysplastic lesions compared to standard endoscopy, and 89%-115% more lesions than non-BE experts. This clinical study evaluates oral administration of bevacizumab-800CW and cetuximab-800CW to improve both lesion detection and shorten the procedure time.

Methods A total of 25 BE patients scheduled for a diagnostic and subsequent therapeutic endoscopy were included. During the dose-finding phase, 4.5 mg and 9.0 mg of the fluorescent tracers bevacizumab-800CW and cetuximab-800CW were evaluated separately in fifteen patients. The optimal dose was determined afterwards. Patients ingested the tracer in two 15 mL sips while in an upright position, 10 minutes prior to qFME. The endoscopic procedure included in vivo fluorescence signal visualization and quantification by multi-diameter single fiber reflectance / single fiber fluorescence (MDSFR/SFF) mucosal spectroscopy measurements. Additionally, biopsies are collected from non-dysplastic Barrett tissue and (suspected) dysplastic tissue for histopathological analysis.

Results Oral administration of both tracers was well-tolerated, with no (severe) adverse events reported. To date, 19 patients have been included. All high-grade dysplastic (HGD) and EAC lesions were detected using standard endoscopy and qFME. QFME demonstrated higher in vivo fluorescence signals in dysplastic tissue compared to non-dysplastic tissue for both tracers and dose groups (target-to-background ratio>2). MDSFR/SFF quantification revealed higher fluorescent intensity in HGD and EAC lesions compared to non-dysplastic BE with 4.5 mg (n=7, p=0.0006) and 9.0 mg bevacizumab-800CW (n=4, p=0.0357). A similar trend was observed in the smaller cetuximab-800CW cohort with 4.5 mg (n=4, p=0.0571), although it did not reach significance with 9.0 mg (n=2, p=ns).

Conclusions This is the first study worldwide to use oral administration of fluorescent tracers to enhance lesion detection in BE patients. Preliminary results suggest that qFME using oral bevacizumab-800CW and cetuximab-800CW is feasible, reduces procedural time, and accurately detects lesions, with an optimal dose of 4.5 mg. Recruitment is ongoing, with five additional patients being enrolled to assess fluorescence signal enhancement and lesion detection with dual-tracer administration. Additionally, five BE patients without dysplasia will be included as a control group to evaluate tracer specificity.

Conflicts of Interest

Authors do not have any conflict of interest to disclose.

Publication History

Article published online:
27 March 2025