The broad, long-term objective of this project is to develop a multi-institutional, multi-disciplinary translational Research Center to accelerate the clinical use of targeted imaging methodologies for the early detection and prevention of esophageal adenocarcinoma through the Barrett's Esophagus Translational Research Network (BETRNet). 3 inter-related Primary Research Projects and Shared Research Resources (Cores) will be established to develop advanced endoscopic imaging as an enabling technology for management of patients with Barrett's esophagus by visualizing molecular targets from amplified and overexpressed genes. In Project 1, genomic data will be analyzed to identify molecular targets based on properties of gene amplification and/or overexpression. These targets will be used to select highly specific peptides in Project 2 that will be fluorescent-labeled for detection on imaging. A multi-spectral scanning fiber endoscope will be developed in Project 3 to perform real time visualization of a panel of peptides in 3 fluorescence channels. The unique instrument design can pass through the working channel of a standard medical endoscope to allow for concurrent white light imaging. Future versions of this instrument may have 12 or more channels. Image processing algorithms will developed to "red-flag" diseased regions on a panoramic view of the distal esophagus. This integrated imaging strategy aims to assist the physician in guiding tissue biopsy of high grade dysplasia and early adenocarcinoma that can not been seen otherwise. Phase 1 studies will be performed to prepare for a future multi-center clinical validation study. Future applications will allow for real time spatial visualization and monitoring of other targets, including those associated with stem cells or with biomarkers of cancer risk. Moreover, imaging of molecular targets can be performed in patients with Barrett's esophagus over time to better understand the molecular mechanisms of this disease. The 3 Cores will support the Primary Research Projects, Pilot Projects, and Cross-BETRNet Projects. The Administrative Core will provide support for grants and regulatory management, including budgets, financial reporting, progress reports, human subjects protocols, investigation of new drug (IND) applications, and Steering Committee representation. The Bioinformatics Core will provide support the Primary Projects for statistical evaluation of genomic, imaging, and clinical data and the BETRNet Network for data sharing and archiving of tissue specimens. The Validation &Pathology Core will provide support for validation of peptide binding activity to amplified and overexpressed gene targets in high-grade dysplasia and early adenocarcinoma.

Public Health Relevance

This research addresses the need for novel methodologies to improve early detection and prevention of esophageal adenocarcinoma in patients with Barrett's esophagus, a disease notable for having the fastest growing incidence of all cancers in the U.S. Targeted imaging provides an enabling technology to guide tissue biopsy and to study molecular mechanisms of cancer transformation over time. More effective cancer preventive measures will benefit not only affected individuals but also the public at large.

Agency
National Institute of Health (NIH)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54CA163059-04
Application #
8724430
Study Section
Special Emphasis Panel (ZCA1)
Program Officer
Richmond, Ellen S
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
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Leicht, Deborah T; Kausar, Tasneem; Wang, Zhuwen et al. (2014) TGM2: a cell surface marker in esophageal adenocarcinomas. J Thorac Oncol 9:872-81
Atreya, Raja; Neumann, Helmut; Neufert, Clemens et al. (2014) In vivo imaging using fluorescent antibodies to tumor necrosis factor predicts therapeutic response in Crohn's disease. Nat Med 20:313-8
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Sturm, Matthew B; Joshi, Bishnu P; Lu, Shaoying et al. (2013) Targeted imaging of esophageal neoplasia with a fluorescently labeled peptide: first-in-human results. Sci Transl Med 5:184ra61
Sturm, Matthew B; Piraka, Cyrus; Elmunzer, B Joseph et al. (2013) In vivo molecular imaging of Barrett's esophagus with confocal laser endomicroscopy. Gastroenterology 145:56-8
Tomizawa, Yutaka; Iyer, Prasad G; Wong Kee Song, Louis M et al. (2013) Safety of endoscopic mucosal resection for Barrett's esophagus. Am J Gastroenterol 108:1440-7; quiz 1448
Khondee, Supang; Wang, Thomas D (2013) Progress in molecular imaging in endoscopy and endomicroscopy for cancer imaging. J Healthc Eng 4:1-22

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