Molecular imaging using fluorescent lectins permits rapid endoscopic identification of dysplasia in Barrett's esophagus

• Published in: Nature medicine Vol. 18; no. 2; pp. 315 - 321
• Main Authors: Bird-Lieberman, Elizabeth L, Neves, André A, Lao-Sirieix, Pierre, O'Donovan, Maria, Novelli, Marco, Lovat, Laurence B, Eng, William S, Mahal, Lara K, Brindle, Kevin M, Fitzgerald, Rebecca C
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.02.2012; Nature Publishing Group
• Subjects: 631/1647/1888/2249; 631/1647/245/2225; 692/699/1503/1476/1322; 692/699/67/1504/1477; Aged; Aged, 80 and over; Barrett Esophagus - diagnosis; Barrett Esophagus - pathology; Barrett's esophagus; Biomedical and Life Sciences; Biomedicine; Cancer Research; Care and treatment; Diagnosis; Diagnostic imaging; Dysplasia; Esophageal Neoplasms - diagnosis; Esophageal Neoplasms - pathology; Esophagoscopy - methods; Esophagus; Esophagus - metabolism; Esophagus - pathology; Female; Fluorescence; Glycosphingolipids - metabolism; Humans; Infectious Diseases; Lectins; Lesions; Male; Medical imaging; Metabolic Diseases; Methods; Middle Aged; Molecular biology; Molecular Imaging - methods; Molecular Medicine; Neurosciences; Patient outcomes; Physiological aspects; Precancerous Conditions - diagnosis; Precancerous Conditions - pathology; Properties; technical-report; Wheat Germ Agglutinins - metabolism; United Kingdom
• ISSN: 1078-8956; 1546-170X
• DOI: 10.1038/nm.2616

Cell-surface glycans are known to alter as Barrett's esophagus progresses to adenocarcinoma, leading to specific changes in lectin binding patterns. Bird-Lieberman and her colleagues have exploited this knowledge to develop a new endoscopic approach that uses fluorescent-labeled lectins to visualize pre-cancerous, high-grade dysplastic lesions in Barrett's esophagus that cannot be detected by conventional endoscopy. The method uses commonly available endoscopic equipment, provides a wide field of view and is shown here in ex vivo esophageal tissue. Barrett's esophagus is an example of a pre-invasive state, for which current endoscopic surveillance methods to detect dysplasia are time consuming and inadequate. The prognosis of cancer arising in Barrett's esophagus is improved by early detection at the stage of mucosal carcinoma or high-grade dysplasia. Molecular imaging methods could revolutionize the detection of dysplasia, provided they permit a wide field of view and highlight abnormalities in real time. We show here that cell-surface glycans are altered in the progression from Barrett's esophagus to adenocarcinoma and lead to specific changes in lectin binding patterns. We chose wheat germ agglutinin as a candidate lectin with clinical potential. The binding of wheat germ agglutinin to human tissue was determined to be specific, and we validated this specific binding by successful endoscopic visualization of high-grade dysplastic lesions, which were not detectable by conventional endoscopy, with a high signal-to-background ratio of over 5.