2-(n-(7-nitrobenz-2-oxa-1-3-diazol-4-yl)amino)-2-deoxyglucose and Esophageal-Neoplasms

The availability of confocal endomicroscopy motivates the development of optical contrast agents that can delineate the morphologic and metabolic features of gastrointestinal neoplasia. This study evaluates 2-NBDG, a fluorescent deoxyglucose, the uptake of which is associated with increased metabolic activity, in the identification of Barrett's-associated neoplasia. Surveillance biopsies from patients with varying pathologic grades of Barrett's esophagus were incubated ex vivo at 37°C with 2-NBDG and imaged with a fluorescence confocal microscope. Images were categorized as neoplastic (high grade dysplasia, esophageal adenocarcinoma) or metaplastic (intestinal metaplasia, low grade dysplasia) based on the degree of glandular 2-NBDG uptake. Classification accuracy was assessed using histopathology as the gold standard. Forty-four biopsies were obtained from twenty-six patients; 206 sites were imaged. The glandular mean fluorescence intensity of neoplastic sites was significantly higher than that of metaplastic sites (p<0.001). Chronic inflammation was associated with increased 2-NBDG uptake in the lamina propria but not in glandular epithelium. Sites could be classified as neoplastic or not with 96% sensitivity and 90% specificity based on glandular mean fluorescence intensity. Classification accuracy was not affected by the presence of inflammation. By delineating the metabolic and morphologic features of neoplasia, 2-NBDG shows promise as a topical contrast agent for confocal imaging. Further in vivo testing is needed to determine its performance in identifying neoplasia during confocal endomicroscopic imaging.

Topics: 4-Chloro-7-nitrobenzofurazan; Adenocarcinoma; Administration, Topical; Algorithms; Area Under Curve; Barrett Esophagus; Biopsy; Contrast Media; Deoxyglucose; Drug Evaluation, Preclinical; Esophageal Neoplasms; Esophagoscopy; Esophagus; Fluorescent Dyes; Goblet Cells; Humans; Microscopy, Confocal; ROC Curve