Targeted Peptide Selection and Validation

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The incidence of esophageal adenocarcinoma has increased significantly over the past 30 years, and the 5-year mortality rate is unacceptably high because of a lack of effective early detection strategies [1]. Moreover, the presence of alarm symptoms that motivate patients to seek medical care often occur when this disease is advanced in stage. Barrett's esophagus is a precursor condition defined by a "salmon pink," columnar-lined segment on endoscopy with histological evidence of intestinal metaplasia [2,3]. Once Barrett's esophagus is diagnosed, endoscopic surveillance is recommended for detection of high-grade dysplasia and early adenocarcinoma [4]. Tarqeted imaging is needed for early detection and prevention of adenocarcinoma because high-grade dysplasia can be focal and patchy [5]. However, white light endoscopy is not sensitive to this condition because dysplasia is architecturally flat and visually indistinct from metaplasia [6]. Consequently, random four quadrant biopsy has been proposed [7], but its effectiveness is limited by sampling error, histology processing costs, and time limitations. Furthermore, the histological diagnosis of dysplasia in Barrett's esophagus is challenging, even for the most experienced pathologists, because dysplasia is difficult to distinguish from reactive changes associated with inflammation [8]. High-frequency amplified chromosomal regions and mRNA over-expression represents biological events that are specific for neoplastic changes not seen in inflammation [9], and their targets can be detected endoscopically with fluorescent-labeled peptides.