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

基本信息

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
项目类别：
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

项目摘要

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，可提供中空器官中上皮的实时宽视野图像，并且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，与远端相比，近端（右）更常见。（左）结肠。临床研究表明，内窥镜检查并没有显着降低结肠癌这一区域的死亡率。腺瘤过度表达上皮生长因子受体 (EGFR)，这代表了密歇根州将优化成像的早期目标。奥林巴斯将优化可见内窥镜，以提高对 Cy5.5 的 NIR 荧光的敏感性。为了将来能够使用其他 NIR 染料，CPC Scientific Inc. 将使用良好生产规范 (GMP) 方法生产肽，由各合作伙伴的成员组成的团队将共同准备向 FDA 提交的使用该肽的监管报告。将在自发性结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，并使用 Good 在动物身上进行严格的药理学毒理学研究。实验室评估肽安全性的实践（GLP）。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，以改进早期方法。近端结肠癌的检测：1) 可检测扁平不典型增生的肽显像剂，2) 提供定量 NIR 图像的荧光内窥镜，3) 支持 EGFR 过表达作为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）、S Lee（CPC Scientific）共同完成。使用 GMP 方法进行临床肽生产的专家，以及进行 FDA 监管的临床研究的专家 DK Turgeon（密歇根州）。