Kara K Rossfeld1, Steven E Justiniano2, Haiming Ding3, Li Gong3, Shankaran Kothandaraman3, Dwitiya Sawant4, Motoyasu Saji2, Chadwick L Wright3, Lawrence S Kirschner2,5, Matthew D Ringel2,5, Michael F Tweedle3, John E Phay1. 1. Department of Surgery, Ohio State University-Wexner Medical Center, Arthur G. James Comprehensive Cancer Center and Ohio State University, Columbus, Ohio 43210. 2. Division of Endocrinology Diabetes and Metabolism, Ohio State University-Wexner Medical Center, Arthur G. James Comprehensive Cancer Center and Ohio State University, Columbus, Ohio 43210. 3. Department of Radiology, Wright Center for Innovation in Biomedical Imaging, Ohio State University-Wexner Medical Center, Arthur G. James Comprehensive Cancer Center and Ohio State University, Columbus, Ohio 43210. 4. Department of Molecular Genetics, Ohio State University-Wexner Medical Center, Arthur G. James Comprehensive Cancer Center and Ohio State University, Columbus, Ohio 43210. 5. Molecular Biology and Cancer Genetics, Ohio State University-Wexner Medical Center, Arthur G. James Comprehensive Cancer Center and Ohio State University, Columbus, Ohio 43210.
Abstract
Context: The primary and definitive treatment of medullary thyroid cancer (MTC) is surgical resection. Recurrent or residual disease is typically a result of incomplete surgical removal. Objective: Our objective is to develop a compound that assists in intraoperative visualization of cancer, which would have the potential to improve surgical cure rates and outcomes. Results: We report the biological characterization of Compound-17, which is labeled with IRdye800, allowing fluorescent visualization of MTC mouse models. We found that the agent has high affinity for two human MTC cell lines (TT and MZ-CRC1) in vitro and in vivo. We further tested the affinity of the compound in a newly developed MTC orthotopic xenograft model and found that Compound-17 produces fluorescent signals within MTC-derived orthotopic xenografts in comparison with a sequence-jumbled control compound and surrounding normal tissues. Conclusions: Compound-17 is a unique and effective molecule for MTC identification that may have therapeutic potential.
Context: The primary and definitive treatment of medullary thyroid cancer (MTC) is surgical resection. Recurrent or residual disease is typically a result of incomplete surgical removal. Objective: Our objective is to develop a compound that assists in intraoperative visualization of cancer, which would have the potential to improve surgical cure rates and outcomes. Results: We report the biological characterization of Compound-17, which is labeled with IRdye800, allowing fluorescent visualization of MTC mouse models. We found that the agent has high affinity for two human MTC cell lines (TT and MZ-CRC1) in vitro and in vivo. We further tested the affinity of the compound in a newly developed MTC orthotopic xenograft model and found that Compound-17 produces fluorescent signals within MTC-derived orthotopic xenografts in comparison with a sequence-jumbled control compound and surrounding normal tissues. Conclusions: Compound-17 is a unique and effective molecule for MTC identification that may have therapeutic potential.
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