Glycan Near-Infrared Imaging Using Fluorescently Labeled Wheat Germ Agglutinin (WGA): Evaluation of Safety and Feasibility in a Prospective Pilot Study

SYNOPSIS Glycan Near-Infrared Imaging Using Fluorescently Labeled Wheat Germ Agglutinin (WGA): Evaluation of Safety and Feasibility in a Prospective Pilot Study

Rationale Early detection of dysplastic and early carcinomas in the esophagus is critical for improving long term survival rates. Patients with Barrett's Esophagus (BE), a precancerous condition, undergo surveillance endoscopies with random four-quadrant biopsies to detect disease progression. However, this approach carries a high risk of sampling error, resulting in a detection miss-rate of up to 37%.

Improved imaging modalities may help facilitate accurate disease detection. For example, several studies have shown that near-infrared quantified fluorescence molecular endoscopy (qFME) could serve as a red flag detection technique to detect invisible tumor lesions and dysplastic tissue during endoscopy.

Cell membrane glycosylation patterns are affected in dysplastic and cancerous tissue formation. Lectins are glycan-binding proteins present in most living organisms, animals, plants and microorganisms. The University Medical Center Groningen (UMCG) developed a fluorescent tracer by labeling the common wheat lectin WGA with the fluorescent dye 800CW to detect early carcinomas in the esophagus. WGA targets the glycans N-acetylneuraminic acid - Neu5Ac (sialic acid - NANA) and N-acetylglucosamine - GlcNAc (NAG), which are dysregulated in the progression of esophageal adenocarcinoma.

WGA-800CW is a low-cost, reliable, plant-derived fluorescent lectin tracer that binds specifically to glycan residues overexpressed on dysplastic epithelial cells. Topical administration has a favorable safety profile and minimizes systemic side effects, as the tracer is topically sprayed on the esophageal mucosa, enabling localized visualization of aberrant glycosylation patterns by near-infrared fluorescence imaging to detect dysplasia and endoscopically invisible tumors.