title: Pre-clinical evaluation of fluorescent deoxyglucose as a topical contrast agent for the detection of Barrett's-associated neoplasia during confocal imaging.
abstract: 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.
authors: Department of Bioengineering, Rice University, 6100 Main St., MS 142, Houston, TX 77005, USA.
authors: N
authors: N
authors: Thekkek
authors: D M
authors: DM
authors: Maru
authors: A D
authors: AD
authors: Polydorides
authors: M S
authors: MS
authors: Bhutani
authors: S
authors: S
authors: Anandasabapathy
authors: R
authors: R
authors: Richards-Kortum
mesh_terms: D009327:4-Chloro-7-nitrobenzofurazan / Q000031:analogs & derivatives*; D000230:Adenocarcinoma / Q000175:diagnosis* / Q000473:pathology; D000287:Administration, Topical; D000465:Algorithms; D019540:Area Under Curve; D001471:Barrett Esophagus / Q000175:diagnosis* / Q000473:pathology; D001706:Biopsy; D003287:Contrast Media; D003847:Deoxyglucose / Q000031:analogs & derivatives*; D004353:Drug Evaluation, Preclinical; D004938:Esophageal Neoplasms / Q000175:diagnosis* / Q000473:pathology; D004945:Esophagoscopy; D004947:Esophagus / Q000473:pathology; D005456:Fluorescent Dyes; D020397:Goblet Cells / Q000473:pathology; D006801:Humans; D018613:Microscopy, Confocal; D012372:ROC Curve
chemical_list: D003287:Contrast Media; D005456:Fluorescent Dyes; D003847:Deoxyglucose; D009327:4-Chloro-7-nitrobenzofurazan; C098340:2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose