Detection of early adenocarcinoma of the esophagogastric junction by spraying an enzyme-activatable fluorescent probe targeting Dipeptidyl peptidase-IV
Detection of early adenocarcinoma of the esophagogastric junction by spraying an enzyme-activatable fluorescent probe targeting Dipeptidyl peptidase-IV
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DOI：
10.1186/s12885-020-6537-9
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发表时间：
2020-01-28
期刊：
影响因子：
3.8
通讯作者：
Sakamoto, Naoya
中科院分区：
文献类型：
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作者：
Yamamoto, Keikokw;Ohnishi, Shunsuke;Sakamoto, Naoya
背景 使用传统内窥镜或图像增强内窥镜检查仍然难以检测和诊断食管胃结合部（EGJ）的早期腺癌。已开发出一种谷氨酰脯氨酰羟甲基罗丹明绿 (EP-HMRG) 荧光探针，该探针可在二肽基肽酶 (DPP)-IV 特异性序列裂解后被酶促激活而发出荧光，据报道可用于检测头颈和食道的鳞状细胞癌；然而，目前缺乏通过荧光分子成像检测EGJ腺癌的研究。因此，我们通过应用 EP-HMRG 并使用内镜粘膜下剥离术 (ESD) 切除的临床样本研究了早期 EGJ 腺癌的可视化。方法对21例ESD切除的临床标本进行EP-HMRG荧光成像，前瞻性测量肿瘤和非肿瘤感兴趣区域的荧光强度。还进行免疫组织化学测定DPP-IV的表达。结果临床样本荧光成像显示，应用EP-HMRG后几分钟内即可看到肿瘤病灶，敏感性、特异性和准确性分别为85.7%、85.7%和85.7%。然而，具有肠化生背景的肿瘤不具有足够的对比背景比，因为完全肠化生也表达DPP-IV。免疫组织化学测量显示所有荧光肿瘤病变均表达 DPP-IV。结论 EP-HMRG 荧光成像可用于检测不具有肠化生背景的早期 EGJ 腺癌病变。
Background It is still difficult to detect and diagnose early adenocarcinoma of the esophagogastric junction (EGJ) using conventional endoscopy or image-enhanced endoscopy. A glutamylprolyl hydroxymethyl rhodamine green (EP-HMRG) fluorescent probe that can be enzymatically activated to become fluorescent after the cleavage of a dipeptidyl peptidase (DPP)-IV-specific sequence has been developed and is reported to be useful for the detection of squamous cell carcinoma of the head and neck, and esophagus; however, there is a lack of studies that focuses on detecting EGJ adenocarcinoma by fluorescence molecular imaging. Therefore, we investigated the visualization of early EGJ adenocarcinoma by applying EP-HMRG and using clinical samples resected by endoscopic submucosal dissection (ESD). Methods Fluorescence imaging with EP-HMRG was performed in 21 clinical samples resected by ESD, and the fluorescence intensity of the tumor and non-tumor regions of interest was prospectively measured. Immunohistochemistry was also performed to determine the expression of DPP-IV. Results Fluorescence imaging of the clinical samples showed that the tumor lesions were visualized within a few minutes after the application of EP-HMRG, with a sensitivity, specificity, and accuracy of 85.7, 85.7, and 85.7%, respectively. However, tumors with a background of intestinal metaplasia did not have a sufficient contrast-to-background ratio since complete intestinal metaplasia also expresses DPP-IV. Immunohistochemistry measurements revealed that all fluorescent tumor lesions expressed DPP-IV. Conclusions Fluorescence imaging with EP-HMRG could be useful for the detection of early EGJ adenocarcinoma lesions that do not have a background of intestinal metaplasia.