Early Detection of Colorectal Cancer on Near-Infrared Molecular Endoscopy

 描述(由申请人提供)：这一学术-产业合作伙伴包括密歇根大学、奥林巴斯医疗系统公司和CPC Science Inc.。内窥镜是一种光学成像技术，可以提供中空器官中的上皮组织的实时广域图像，被患者广泛接受用于结直肠癌的监测。外观平坦的癌前病变不能在白光照射下看到，与远端(左)结肠相比，更常发现在近端(右)。临床研究表明，内窥镜检查并没有显著降低这一结肠区域癌症的死亡率。上皮生长因子受体(EGFR)在腺瘤中过度表达，是早期成像的靶点。密歇根州将优化一种针对EGFR的肽，并将其标记为Cy5.5，一种明亮的近红外(NIR)染料。奥林巴斯将优化可见内窥镜，以提高对Cy5.5的近红外荧光的敏感度。光学设计将是灵活的，允许在未来使用其他近红外染料。CPC Science Inc.将使用良好制造规范(GMP)方法生产这些多肽。一个由每个合作伙伴的成员组成的团队将共同准备提交给FDA的监管提交文件，以便将这种新的成像剂和仪器用于“首例人类”临床研究。多肽安全性、特异性和药代动力学的早期证据将在自发性结直肠癌小鼠模型中建立。将使用良好实验室规范(GLP)在动物身上进行严格的药理学和毒理学研究，以评估多肽的安全性。我们将建立这种多肽用于检测n=25名患者近端结肠腺瘤的安全性和早期有效性证据。这项工作将为研究和医学界提供新的成像能力，以改进近端结肠癌的早期检测方法：1)可以检测扁平不典型增生的基于多肽的显像剂，2)提供定量近红外图像的荧光内窥镜，以及3)支持EGFR过度表达作为近端结肠癌非典型增生成像生物标志物的临床数据。这项合作工作将由肽类显像剂开发专家TD Wang(密歇根)、先进内窥镜系统专家N Doguchi(奥林巴斯)、使用GMP方法临床生产多肽的专家S·李(CPC Science)和进行FDA规定的临床研究的专家DK Turjo(密歇根)执行。

 DESCRIPTION (provided by applicant): This Academic-Industrial Partnership includes the University of Michigan, Olympus Medical Systems Corp, and CPC Scientific Inc. Endoscopy is an optical imaging technique that provides real time wide-field images of the epithelium in hollow organs, and is widely accepted by patients for surveillance of colorectal cancer. Pre-malignant lesions that are flat in appearance cannot be seen with white light illumination, and are found more often in the proximal (right) compared to the distal (left) colon. Clinical studies have shown that endoscopy has not significantly reduced mortality from cancers that arise in this region of colon. Epithelial growth factor receptor (EGFR) is overexpressed by adenomas, and represents an early target for imaging. Michigan will optimize a peptide that is specific for EGFR and label with Cy5.5, a bright near-infrared (NIR) dye. Olympus will optimize a visible endoscope for sensitivity to NIR fluorescence from Cy5.5. The optical design will be flexible to allow for other NIR dyes to be used in the future. CPC Scientific Inc. will produce the peptides using Good Manufacturing Practices (GMP) methods. A team consisting of members from each partner will jointly prepare the regulatory submission to the FDA to use this new imaging agent and instrument in a "first-in-humans" clinical study. Early evidence of peptide safety, specificity and pharmacokinetics will be established in a mouse model of spontaneous colorectal cancer. A rigorous pharmacology toxicology study will be performed in animals using Good Laboratory Practices (GLP) to evaluate peptide safety. We will establish safety and early evidence of efficacy for this peptide to detect proximal colonic adenomas in n=25 patients. This work will provide the research and medical community with new imaging capabilities for improved methods for early detection of proximal colon cancer: 1) a peptide-based imaging agent that can detect flat dysplasia, 2) a fluorescence endoscope that provides quantitative NIR images, and 3) clinical data to support EGFR over expression as an imaging biomarker for proximal colonic dysplasia. This collaborative work will be performed by TD Wang (Michigan), an expert in the development of peptide-based imaging agents, N Doguchi (Olympus), an expert in advanced endoscopy systems, S Lee (CPC Scientific), an expert in clinical peptide production using GMP methods, and DK Turgeon (Michigan), an expert in conducting FDA regulated clinical studies.