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Accurate Co-Localization of Luciferase Expression and Fluorescent Anti-CEA Antibody Targeting of Liver Metastases in an Orthotopic Mouse Model of Colon Cancer
by
, ,
Kyung-Ha Lee
1,2,3, 
Kristin E. Cox
1,2,
Siamak Amirfakhri
1,2,
Sunidhi Jaiswal
1,2,
Shanglei Liu
1,2,
Mojgan Hosseini
4,
Thinzar M. Lwin
5
,
Paul J. Yazaki
6,
Robert M. Hoffman
1,2,7 and
Michael Bouvet
1,2,* 1
Department of Surgery, University of California San Diego, La Jolla, CA 92037, USA
2
VA San Diego Healthcare System, La Jolla, CA 92161, USA
3
Department of Colorectal Surgery, Chungnam National University Hospital, Daejeon 35015, Republic of Korea
4
Department of Pathology, University of California San Diego, La Jolla, CA 92037, USA
5
Department of Surgical Oncology, City of Hope, Duarte, CA 91010, USA
6
Department of Immunology and Theranostics, Beckman Research Institute, City of Hope, Duarte, CA 91010, USA
7
AntiCancer Inc., San Diego, CA 92111, USA
*
Author to whom correspondence should be addressed.
Cancers 2024, 16(19), 3341; https://doi.org/10.3390/cancers16193341 (registering DOI)
Submission received: 1 September 2024
/
Revised: 23 September 2024
/
Accepted: 26 September 2024
/
Published: 29 September 2024
(This article belongs to the Special Issue Recent Advance in Colorectal Cancer Liver Metastases)
Simple Summary
The present study demonstrated that a humanized anti-CEA antibody conjugated to a near-infrared dye accurately co-localized with luciferase expressing colorectal cancer liver metastases in an orthotopic mouse model. The present study validates the metastatic tumor targeting specificity of the anti-CEA antibody.
Abstract
Background: The present study aimed to validate the accuracy of a tumor-specific antibody to target liver metastases of colorectal cancer. Methods: A humanized anti-CEA antibody conjugated to a fluorescent dye (M5A-IR800) was tested for targeting human colorectal cancer liver metastases (CRLMs) expressing luciferase in an orthotopic mouse model. Orthotopic mouse models of CRLMs were established by implanting fragments of a luciferase-expressing human colorectal cancer cell line, LS174T, in the liver of nude mice. Mice received 50 µg M5A-IR800 72 h prior to imaging. To test co-localization, bioluminescence imaging was performed using D-luciferin, which was given via intraperitoneal injection just prior to imaging. Results: Tumors were able to be visualized non-invasively through the skin with the luciferase–luciferin signal. Intra-abdominal imaging showed accurate labeling of CRLMs with M5A-IR800, which co-localized with the luciferase–luciferin signal. Conclusions: The present results validate the accuracy of a tumor-specific anti-CEA antibody in targeting liver metastases of colorectal cancer.
