Humanized Anti-Tumor-Associated Glycoprotein-72 for Submillimeter Near-Infrared Detection of Colon Cancer in Metastatic Mouse Models.

Abstract

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.

• Authors: Hannah M Hollandsworth, Siamak Amirfakhri, Filemoni Filemoni, Robert M Hoffman, Justin Molnar, Paul J Yazaki, Michael Bouvet
• Journal: The Journal of surgical research (J Surg Res) Vol. 252 Pg. 16-21 (08 2020) ISSN: 1095-8673 [Electronic] United States
• PMID: 32217350 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2020 Elsevier Inc. All rights reserved.

Chemical References

• Alkanesulfonic Acids
• Antibodies, Monoclonal, Humanized
• Antibodies, Neoplasm
• Antigens, Neoplasm
• B72.3 antibody
• Fluorescent Dyes
• IRDye 800CW NHS ester
• Immunoconjugates
• Indoles
• tumor-associated antigen 72

Topics

• Alkanesulfonic Acids (administration & dosage, chemistry)
• Animals
• Antibodies, Monoclonal, Humanized (administration & dosage, immunology)
• Antibodies, Neoplasm (administration & dosage, chemistry, immunology)
• Antigens, Neoplasm (immunology)
• Cell Line, Tumor
• Colonic Neoplasms (diagnostic imaging, immunology, pathology, surgery)
• Fluorescent Dyes (administration & dosage, chemistry)
• Humans
• Immunoconjugates (administration & dosage, chemistry, immunology)
• Indoles (administration & dosage, chemistry)
• Mice
• Peritoneal Neoplasms (diagnostic imaging, immunology, secondary, surgery)
• Preoperative Care (methods)
• Spectroscopy, Near-Infrared (methods)
• Surgery, Computer-Assisted (methods)
• Xenograft Model Antitumor Assays