Department of Radiology , Memorial Sloan Kettering Cancer Center , New York , New York 10065 , United States.
Department of Pediatrics , Stanford University , Stanford , California 94305 , United States.
ACS Nano. 2019 Feb 26;13(2):1354-1364. doi: 10.1021/acsnano.8b06808. Epub 2019 Feb 4.
Cancers of the gastrointestinal (GI) tract are among the most frequent and most lethal cancers worldwide. An important reason for this high mortality is that early disease is typically asymptomatic, and patients often present with advanced, incurable disease. Even in high-risk patients who routinely undergo endoscopic screening, lesions can be missed due to their small size or subtle appearance. Thus, current imaging approaches lack the sensitivity and specificity to accurately detect incipient GI tract cancers. Here we report our finding that a single dose of a high-sensitivity surface-enhanced resonance Raman scattering nanoparticle (SERRS-NP) enables reliable detection of precancerous GI lesions in animal models that closely mimic disease development in humans. Some of these animal models have not been used previously to evaluate imaging probes for early cancer detection. The studies were performed using a commercial Raman imaging system, a newly developed mouse Raman endoscope, and finally a clinically applicable Raman endoscope for larger animal studies. We show that this SERRS-NP-based approach enables robust detection of small, premalignant lesions in animal models that faithfully recapitulate human esophageal, gastric, and colorectal tumorigenesis. This method holds promise for much earlier detection of GI cancers than currently possible and could lead therefore to marked reduction of morbidity and mortality of these tumor types.
胃肠道（GI）癌症是全球最常见和最致命的癌症之一。这种高死亡率的一个重要原因是早期疾病通常没有症状，患者常常出现晚期、无法治愈的疾病。即使在常规进行内镜筛查的高危患者中，由于病变较小或外观细微，也可能会漏诊。因此，目前的成像方法缺乏敏感性和特异性来准确检测早期胃肠道癌症。在这里，我们报告了我们的发现，即单次高灵敏度表面增强共振拉曼散射纳米颗粒（SERRS-NP）剂量可可靠地检测出与人密切相似的疾病发展的动物模型中的癌前 GI 病变。其中一些动物模型以前没有用于评估早期癌症检测的成像探针。这些研究使用商业拉曼成像系统、新开发的小鼠拉曼内窥镜，最后是用于更大动物研究的临床适用的拉曼内窥镜进行。我们表明，这种基于 SERRS-NP 的方法能够可靠地检测出在动物模型中忠实再现人类食管、胃和结直肠肿瘤发生的小的、癌前病变。与目前可能的情况相比，这种方法有望更早地发现胃肠道癌症，从而显著降低这些肿瘤类型的发病率和死亡率。
