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Fluorophore-conjugated anti-CEA Antibody for the Intraoperative Imaging of Pancreatic and Colorectal Cancer
Authors:Sharmeela Kaushal  Michele K. McElroy  George A. Luiken  Mark A. Talamini  A. R. Moossa  Robert M. Hoffman  Michael Bouvet
Affiliation:(1) Department of Surgery, University of California San Diego, Moores Cancer Center, 3855 Health Sciences Drive #0987, La Jolla, CA 92093-0987, USA;(2) OncoFluor, Inc., San Diego, CA, 1211 Alameda Blvd, Coronado, CA 92118, USA;(3) AntiCancer, Inc., San Diego, CA, 7917 Ostrow St, San Diego, CA 92111, USA
Abstract:Introduction  Colorectal and pancreatic cancers together comprise the third and fourth most common causes of cancer-related death in the United States. In both of these cancers, complete detection of primary and metastatic lesions at the time of surgery is critical to optimal surgical resection and appropriate patient treatment. Materials and Methods  We have investigated the use of fluorophore-labeled anti-carcinoembryonic antigen (CEA) monoclonal antibody to aid in cancer visualization in nude mouse models of human colorectal and pancreatic cancer. Anti-CEA was conjugated with a green fluorophore. Subcutaneous, orthotopic primary and metastatic human pancreatic and colorectal tumors were easily visualized with fluorescence imaging after administration of conjugated anti-CEA. The fluorescence signal was detectable 30 min after systemic antibody delivery and remained present for 2 weeks, with minimal in vivo photobleaching after exposure to standard operating room lighting. Tumor resection techniques revealed improved ability to resect labeled tumor tissue under fluorescence guidance. Comparison of two different fluorophores revealed differences in dose–response and photobleaching in vivo. Conclusion  These results indicate that fluorophore-labeled anti-CEA offers a novel intraoperative imaging technique for enhanced visualization of tumors in colorectal and pancreatic cancer when CEA expression is present, and that the choice of fluorophore significantly affects the signal intensity in the labeled tumor. These data were presented at the Society for Surgery of the Alimentary Tract meeting as part of the Digestive Diseases Week, San Diego CA, May 21 2008. Sharmeela Kaushal and Michele K. McElroy shared authorship. Work supported in part by: Cancer Therapeutics Training Program (T32 CA121938) National Institutes of Health (CA109949-03) American Cancer Society (RSG-05-037-01-CCE).
Keywords:Pancreatic neoplasms  Colorectal neoplasms  Carcinoembryonic antigen  Fluorescent antibody technique  Nude mouse cancer models  Fluorescence-guided surgery
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