Humanized Anti–Tumor-Associated Glycoprotein–72 for Submillimeter Near-Infrared Detection of Colon Cancer in Metastatic Mouse Models
| Autor: | Siamak Amirfakhri, Paul J. Yazaki, Hannah M. Hollandsworth, Michael Bouvet, Justin Molnar, Robert M. Hoffman, Filemoni Filemoni |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Fluorescence-lifetime imaging microscopy
Pathology medicine.medical_specialty Immunoconjugates Indoles Antibodies Neoplasm Colorectal cancer medicine.medical_treatment Antibodies Monoclonal Humanized Article Mice 03 medical and health sciences Cecum 0302 clinical medicine Peritoneum Antigen Antigens Neoplasm Cell Line Tumor Laparotomy Preoperative Care medicine Animals Humans Peritoneal Neoplasms Fluorescent Dyes chemistry.chemical_classification Spectroscopy Near-Infrared biology business.industry medicine.disease Xenograft Model Antitumor Assays medicine.anatomical_structure Alkanesulfonic Acids Surgery Computer-Assisted chemistry 030220 oncology & carcinogenesis Colonic Neoplasms biology.protein 030211 gastroenterology & hepatology Surgery Antibody Glycoprotein business |
| Zdroj: | J Surg Res |
| ISSN: | 0022-4804 |
| DOI: | 10.1016/j.jss.2020.02.017 |
| Popis: | Background Tumor-associated glycoprotein (TAG)–72 is a pancarcinoma antigen that is overexpressed in greater than 80% of colorectal adenocarcinomas. CC49 is a TAG-72–specific antibody. The aim of the present study was to demonstrate selective imaging of colon tumors and metastases with the humanized TAG-72 antibody (anti-huCC49) conjugated to a near-infrared fluorophore in orthotopic mouse models. Methods Anti-huCC49 was conjugated to near-infrared dye IR800CW. Mouse imaging was performed with the Pearl Trilogy Small Animal and FLARE Imaging Systems. Subcutaneous mouse models of colon cancer cell line LS174T were used to determine the optimal dose of administration and timing of imaging. Orthotopic mouse models of LS174T were established by surgical orthotopic implantation of LS174T tumors onto the serosa of the cecum. Peritoneal carcinomatosis models were established by injection of LS174T cells into the peritoneum of nude mice. Mice were administered anti-huCC49–IR800 via tail vein injection. Mice were euthanized 72 h later and imaged after laparotomy. Results Subcutaneous LS174T xenografts demonstrated optimal tumor detection 72 h after administration with 50 μg anti-huCC49-IR800CW. Tumors were visualized with fluorescence imaging with a mean tumor-to-liver ratio of 7.39 (standard deviation: 2.76). In the orthotopic model, metastases smaller than 1 mm were fluorescently visualized that were invisible with bright light. Conclusions Anti-huCC49–IR800CW provides sensitive and specific imaging of colon cancer and metastases at a submillimeter resolution in metastatic nude mice models. This provides a promising near-infrared probe for the imaging of colon cancer and metastases for preoperative diagnosis and fluorescence-guided surgery. |
| Databáze: | OpenAIRE |
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