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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：
9922878
负责人：
Thomas D Wang
金额：
$ 43.72万
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 2022-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9922878
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 Cancer Communities Complex Detection Development Devices Disease Distal Drug Kinetics Dysplasia Early Diagnosis Endoscopes Endoscopy Epithelial Epithelium Esophagus Extracellular Domain Fluorescence Future Gene Amplification Gene Frequency Growth Factor Receptors Head and neck structure Human Image Imaging Device Imaging Techniques Immunohistochemistry In Vitro Industry Investigational New Drug Application Label Lead Left Lesion Light Lighting Malignant Neoplasms Medical Medical Device Methods Michigan Molecular Molecular Probes Molecular Target Monitor Morphology Near-infrared optical imaging Optics Organ Pancreas Patients Peptide Receptor Peptide Synthesis Peptides Phage Display Pharmacology and Toxicology Polyps Production Research Research Personnel Resected Resources Safety Screening for cancer Sensitivity and Specificity Specificity Stomach Structural Models Structure System Techniques Time Tissues Topical application Translations Universities Validation Visualization Work adenoma base colon dysplasia colorectal cancer screening cyanine dye 5 design experimental study first-in-human flexibility good laboratory practice imaging agent imaging biomarker imaging capabilities improved in vivo in vivo imaging system industry partner instrument large scale production member mortality mouse model multimodality near infrared dye novel optical imaging overexpression premalignant prevent programs prototype public health relevance receptor receptor expression response 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.