Early Detection of Colorectal Cancer on Near-Infrared Molecular Endoscopy

 描述（由申请人提供）：该学术-工业合作伙伴关系包括密歇根大学，奥林巴斯医疗系统公司和CPC科学公司。内窥镜检查是一种光学成像技术，可提供中空器官中上皮的真实的时间宽视野图像，并被患者广泛接受用于监测结直肠癌。外观平坦的癌前病变在白色光照射下无法看到，并且与远端（左侧）结肠相比，在近端（右侧）更常见。临床研究表明，内窥镜检查并没有显着降低结肠这一区域癌症的死亡率。上皮生长因子受体（EGFR）在腺瘤中过表达，是早期成像的靶点。 密歇根大学将优化一种对EGFR具有特异性的肽，并用明亮的近红外（NIR）染料Cy5.5标记。奥林巴斯将优化可见内窥镜，以提高对Cy5.5近红外荧光的灵敏度。光学设计将是灵活的，以允许在未来使用其他近红外染料。CPC Scientific Inc.将使用良好生产规范（GMP）方法生产肽。由每个合作伙伴的成员组成的团队将共同准备向FDA提交的监管申请，以在“首次人体”临床研究中使用这种新的成像剂和仪器。将在自发性结肠直肠癌小鼠模型中建立肽安全性、特异性和药代动力学的早期证据。将使用药物非临床研究质量管理规范（GLP）在动物中进行严格的药理学毒理学研究，以评价肽的安全性。我们将在n=25例患者中建立这种肽检测近端结肠腺瘤的安全性和有效性的早期证据。 这项工作将为研究和医学界提供新的成像能力，以改进近端结肠癌早期检测的方法：1）基于肽的成像剂，可以检测扁平异型增生，2）荧光内窥镜，提供定量NIR图像，3）临床数据，以支持EGFR过表达作为近端结肠异型增生的成像生物标志物。 这项合作工作将由肽类显像剂开发专家TD Wang（密歇根州）、先进内窥镜系统专家N Doguchi（奥林巴斯）、使用GMP方法生产临床肽类的专家S Lee（CPC Scientific）和进行FDA监管临床研究的专家DK Turgeon（密歇根州）进行。

 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.