Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
Sci Transl Med. 2013 May 8;5(184):184ra61. doi: 10.1126/scitranslmed.3004733.
Esophageal adenocarcinoma is rising rapidly in incidence and usually develops from Barrett's esophagus, a precursor condition commonly found in patients with chronic acid reflux. Premalignant lesions are challenging to detect on conventional screening endoscopy because of their flat appearance. Molecular changes can be used to improve detection of early neoplasia. We have developed a peptide that binds specifically to high-grade dysplasia and adenocarcinoma. We first applied the peptide ex vivo to esophageal specimens from 17 patients to validate specific binding. Next, we performed confocal endomicroscopy in vivo in 25 human subjects after topical peptide administration and found 3.8-fold greater fluorescence intensity for esophageal neoplasia compared with Barrett's esophagus and squamous epithelium with 75% sensitivity and 97% specificity. No toxicity was attributed to the peptide in either animal or patient studies. Therefore, our first-in-human results show that this targeted imaging agent is safe and may be useful for guiding tissue biopsy and for early detection of esophageal neoplasia and potentially other cancers of epithelial origin, such as bladder, colon, lung, pancreas, and stomach.
食管腺癌的发病率正在迅速上升，通常起源于 Barrett 食管，这是一种在慢性胃酸反流患者中常见的前驱病变。由于其扁平外观，常规筛查内镜难以检测到癌前病变。分子变化可用于提高早期肿瘤的检测率。我们开发了一种可特异性结合高级别异型增生和腺癌的肽。我们首先将该肽进行离体应用于 17 名患者的食管标本，以验证其特异性结合。接下来，我们对 25 名患者进行了局部肽给药后的共聚焦内镜检查，发现与 Barrett 食管和鳞状上皮相比，食管肿瘤的荧光强度增加了 3.8 倍，具有 75%的灵敏度和 97%的特异性。在动物和患者研究中均未发现该肽有任何毒性。因此，我们的首次人体研究结果表明，这种靶向成像剂是安全的，可能有助于指导组织活检，以及早期发现食管肿瘤，并且可能对其他上皮来源的癌症（如膀胱癌、结肠癌、肺癌、胰腺癌和胃癌）也具有一定的作用。
