Use of monoclonal antibody–IRDye800CW bioconjugates in the resection of breast cancer

• Published in: The Journal of surgical research 2014-05, Vol.188 (1), p.119-128
• Main Authors: Korb, Melissa L., MD, Hartman, Yolanda E., BS, Kovar, Joy, MS, Zinn, Kurt R., PhD, DVM, Bland, Kirby I., MD, Rosenthal, Eben L., MD
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Monoclonal, Humanized; Antibody; Benzenesulfonates; Breast - pathology; Breast - surgery; Breast cancer; Breast Neoplasms - pathology; Breast Neoplasms - surgery; Cell Line, Tumor; Female; Fluorescence; Humans; Indoles; Infrared Rays; Intraoperative Care - methods; Intraoperative Period; Mice, Nude; Near-infrared; Optical Imaging; Surgery
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1016/j.jss.2013.11.1089

Abstract Background Complete surgical resection of breast cancer is a powerful determinant of patient outcome, and failure to achieve negative margins results in reoperation in between 30% and 60% of patients. We hypothesize that repurposing Food and Drug Administration–approved antibodies as tumor-targeting diagnostic molecules can function as optical contrast agents to identify the boundaries of malignant tissue intraoperatively. Materials and methods The monoclonal antibodies bevacizumab, cetuximab, panitumumab, trastuzumab, and tocilizumab were covalently linked to a near-infrared fluorescence probe (IRDye800CW) and in vitro binding assays were performed to confirm ligand-specific binding. Nude mice bearing human breast cancer flank tumors were intravenously injected with the antibody–IRDye800 bioconjugates and imaged over time. Tumor resections were performed using the SPY and Pearl Impulse systems, and the presence or absence of tumor was confirmed by conventional and fluorescence histology. Results Tumor was distinguishable from normal tissue using both SPY and Pearl systems, with both platforms being able to detect tumor as small as 0.5 mg. Serial surgical resections demonstrated that real-time fluorescence can differentiate subclinical segments of disease. Pathologic examination of samples by conventional and optical histology using the Odyssey scanner confirmed that the bioconjugates were specific for tumor cells and allowed accurate differentiation of malignant areas from normal tissue. Conclusions Human breast cancer tumors can be imaged in vivo with multiple optical imaging platforms using near-infrared fluorescently labeled antibodies. These data support additional preclinical investigations for improving the surgical resection of malignancies with the goal of eventual clinical translation.