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.

Public Health Relevance

Colon cancer is a leading cause of worldwide cancer-related deaths. Pre-malignant lesions that are flat in appearance are difficult to see with conventional white light endoscopy. EGFR is a promising molecular target that is found at an early stage of disease, and can be detected with a near-infrared endoscope to prevent future development of cancer. A partnership between academia and industry is needed to accelerate delivery of the imaging agent and instrument into the clinic.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA193377-03
Application #
9477498
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Hartshorn, Christopher
Project Start
2016-05-15
Project End
2021-04-30
Budget Start
2018-05-01
Budget End
2019-04-30
Support Year
3
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Joshi, Bishnu P; Wang, Thomas D (2018) Targeted Optical Imaging Agents in Cancer: Focus on Clinical Applications. Contrast Media Mol Imaging 2018:2015237
Chen, Yan; Zhou, Quan; Li, Xue et al. (2017) Ultrasmall Paramagnetic Iron Oxide Nanoprobe Targeting Epidermal Growth Factor Receptor for In Vivo Magnetic Resonance Imaging of Hepatocellular Carcinoma. Bioconjug Chem 28:2794-2803
Li, Gaoming; Li, Haijun; Duan, Xiyu et al. (2017) Visualizing Epithelial Expression in Vertical and Horizontal Planes With Dual Axes Confocal Endomicroscope Using Compact Distal Scanner. IEEE Trans Med Imaging 36:1482-1490
Joshi, Bishnu P; Dai, Zhenzhen; Gao, Zhenghong et al. (2017) Detection of Sessile Serrated Adenomas in the Proximal Colon Using Wide-Field Fluorescence Endoscopy. Gastroenterology 152:1002-1013.e9
Duan, Xiyu; Li, Haijun; Zhou, Juan et al. (2016) Visualizing epithelial expression of EGFR in vivo with distal scanning side-viewing confocal endomicroscope. Sci Rep 6:37315
Joshi, Bishnu P; Zhou, Juan; Pant, Asha et al. (2016) Design and Synthesis of Near-Infrared Peptide for in Vivo Molecular Imaging of HER2. Bioconjug Chem 27:481-94
Rabinsky, Emily F; Joshi, Bishnu P; Pant, Asha et al. (2016) Overexpressed Claudin-1 Can Be Visualized Endoscopically in Colonic Adenomas In Vivo. Cell Mol Gastroenterol Hepatol 2:222-237
Zhou, Quan; Li, Zhao; Zhou, Juan et al. (2016) In vivo photoacoustic tomography of EGFR overexpressed in hepatocellular carcinoma mouse xenograft. Photoacoustics 4:43-54
Joshi, Bishnu P; Pant, Asha; Duan, Xiyu et al. (2016) Multimodal Video Colonoscope for Targeted Wide-Field Detection of Nonpolypoid Colorectal Neoplasia. Gastroenterology 150:1084-1086