Early Detection of Colorectal Cancer on Near-Infrared Molecular Endoscopy

近红外分子内窥镜早期发现结直肠癌

• 批准号: 9030043
• 负责人: Thomas D Wang
• 金额: $ 40.32万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-05-15 至 2021-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9030043
• 关键词: Academia; Address; Affinity; Animals; Antibodies; Appearance; Binding; Cell surface; Cells; Cessation of life; Clinic; Clinical; Clinical Data; Clinical Research; Colon; Colon Carcinoma; Colonic Adenoma; Colonoscopy; Colorectal; Colorectal Cancer; Communities; Complex; Detection; Development; Devices; Disease; Distal; Drug Kinetics; Dyes; Dysplasia; Early Diagnosis; Endoscopes; Endoscopy; Epithelial; Epithelium; Esophagus; Fluorescence; Future; Gene Frequency; Growth Factor Receptors; Head and neck structure; Human; Image; Imagery; Imaging Device; Imaging Techniques; Immunohistochemistry; In Vitro; Industry; Investigation; Label; Lead; Left; Lesion; Light; Lighting; Malignant Neoplasms; Medical; Medical Device; Medical Research; Methods; Michigan; Molecular; Molecular Probes; Molecular Target; Monitor; Morphology; Near-infrared optical imaging; Optics; Organ; Pancreas; Patients; Peptide Synthesis; Peptides; Phage Display; Pharmacology and Toxicology; Polyps; Premalignant; Production; Qualifying; Research Personnel; Resected; Resources; Safety; Screening for cancer; Sensitivity and Specificity; Specificity; Staging; Stomach; Structural Models; Structure; System; Techniques; Time; Tissues; Topical application; Translations; Universities; Validation; Work; adenoma; base; colon dysplasia; colorectal cancer screening; design; flexibility; good laboratory practice; imaging agent; imaging biomarker; imaging system; improved; in vivo; in vivo imaging; industry partner; instrument; large scale production; member; mortality; mouse model; novel; novel therapeutics; optical imaging; overexpression; prevent; programs; prototype; public health relevance; receptor; receptor expression; research study; response; screening; stability testing; targeted imaging

 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.

 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 Scientific Inc。内窥镜检查是一种光学成像技术，可提供中空器官上皮的实时宽视野图像，并被患者广泛接受用于监测结直肠癌。白光照明下无法看到外观平坦的癌前病变，与远端（左）结肠相比，近端（右）结肠更常见。临床研究表明，内窥镜检查并没有显着降低该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，是成像的早期靶点。 密歇根州将优化一种 EGFR 特异性肽，并用 Cy5.5（一种明亮的近红外 (NIR) 染料）进行标记。奥林巴斯将优化可见内窥镜对 Cy5.5 近红外荧光的敏感性。光学设计将非常灵活，以便将来可以使用其他近红外染料。 CPC Scientific Inc. 将使用良好生产规范 (GMP) 方法生产这些肽。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“人类首次”临床研究中使用这种新的成像剂和仪器。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毒理学研究，以评估肽的安全性。我们将建立该肽在 n=25 名患者中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）一种基于肽的成像剂，可以检测扁平不典型增生，2）一种提供定量近红外图像的荧光内窥镜，3）支持EGFR过度表达作为近端结肠不典型增生的成像生物标志物的临床数据。 这项合作工作将由肽显像剂开发专家 TD Wang（密歇根州）、先进内窥镜系统专家 N Doguchi（奥林巴斯）、使用 GMP 方法进行临床肽生产的专家 S Lee（CPC Scientific）和 FDA 监管临床研究专家 DK Turgeon（密歇根州）共同完成。