Targeted Peptide Selection and Validation

在过去的30年里，食管腺癌的发病率显著增加 五年的死亡率高得令人无法接受，因为缺乏有效的早期发现 战略[1]。此外，当疾病进展到晚期时，往往会出现促使患者寻求医疗护理的警报症状。Barrett‘s食道是一种前驱症状，内窥镜下可见“鲑鱼粉红色”柱状衬里的节段，组织学证据为肠化[2，3]。 一旦诊断出Barrett‘s食道，建议对高度不典型增生和早期腺癌进行内窥镜监测[4]。对于腺癌的早期发现和预防，靶点成像是必要的，因为高度不典型增生可能是局灶性的和斑片状的[5]。然而，白光内窥镜检查对这种情况不敏感，因为异型增生在结构上是平坦的，在视觉上与化生不明显[6]。 因此，随机四象限活检被提出[7]，但其有效性受到抽样误差、组织学处理成本和时间限制的限制。此外，Barrett‘s食道异型增生的组织学诊断具有挑战性，即使对最有经验的病理学家也是如此，因为异型增生很难与炎症相关的反应性改变区分[8]。高频放大的染色体区域和mRNA的过度表达代表了炎症中未见的肿瘤性变化所特有的生物事件[9]，其靶标可以通过荧光标记的多肽通过内窥镜检测到。

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.