Hannah M Hollandsworth1,2,3, Hiroto Nishino1,4, Michael Turner1,2, Siamak Amirfakhri1,2,3, Filemoni Filemoni1,2,3, Robert M Hoffman1,2,3,4, Paul J Yazaki5, Michael Bouvet6,3,3. 1. Department of Surgery, University of California San Diego, San Diego, CA, U.S.A. 2. Moores Cancer Center, University of California San Diego, San Diego, CA, U.S.A. 3. Department of Surgery, VA San Diego Healthcare System, San Diego, CA, U.S.A. 4. AntiCancer, Inc., San Diego, CA, U.S.A. 5. Department of Molecular Imaging and Therapy, Beckman Research Institute of the City of Hope, Duarte, CA, U.S.A. 6. Department of Surgery, University of California San Diego, San Diego, CA, U.S.A. mbouvet@ucsd.edu.
Abstract
BACKGROUND/AIM: Fluorescence imaging has been shown to improve intra-operative detection of liver metastasis. The present study aimed to determine whether humanized anti-TAG-72 antibody (huCC49) conjugated to a near-infrared dye provides selective labeling of colorectal-cancer liver metastasis in orthotopic mouse models. MATERIALS AND METHODS: Humanized anti-TAG-72 (huCC49) was conjugated to IRDye800CW (huCC49-IR800). Orthotopic liver-metastasis nude-mouse models (n=5) were established with the human colon-cancer LS174T cell-line. Three weeks later, mice were administered huCC49-IR800 and intra-vital imaging was performed 48 h later. The mean tumor-to-liver ratio (TLR) was calculated. RESULTS: Intra-vital imaging demonstrated clear tumor margins with minimal liver fluorescence 48 h after administration of 50 μg huCC49-IR800 with mean TLR=7.53 (SD±2.76). CONCLUSION: Anti-TAG-72 monoclonal antibody conjugated to IRDye800 provides distinct and bright labeling of colorectal tumors in orthotopic nude-mouse models of liver metastasis. TAG-72 may be a useful target for intra-operative imaging of colorectal cancer liver metastasis in the clinic. Copyright
BACKGROUND/AIM: Fluorescence imaging has been shown to improve intra-operative detection of liver metastasis. The present study aimed to determine whether humanized anti-TAG-72 antibody (huCC49) conjugated to a near-infrared dye provides selective labeling of colorectal-cancer liver metastasis in orthotopic mouse models. MATERIALS AND METHODS: Humanized anti-TAG-72 (huCC49) was conjugated to IRDye800CW (huCC49-IR800). Orthotopic liver-metastasis nude-mouse models (n=5) were established with the humancolon-cancerLS174T cell-line. Three weeks later, mice were administered huCC49-IR800 and intra-vital imaging was performed 48 h later. The mean tumor-to-liver ratio (TLR) was calculated. RESULTS: Intra-vital imaging demonstrated clear tumor margins with minimal liver fluorescence 48 h after administration of 50 μg huCC49-IR800 with mean TLR=7.53 (SD±2.76). CONCLUSION: Anti-TAG-72 monoclonal antibody conjugated to IRDye800 provides distinct and bright labeling of colorectal tumors in orthotopic nude-mouse models of liver metastasis. TAG-72 may be a useful target for intra-operative imaging of colorectal cancer liver metastasis in the clinic. Copyright
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Authors: Michael A Turner; Thinzar M Lwin; Siamak Amirfakhri; Hiroto Nishino; Robert M Hoffman; Paul J Yazaki; Michael Bouvet Journal: Biomolecules Date: 2021-12-02