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Development of a humanized anti-CEA antibody for fluorescent guided surgery of GI cancers
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Paper Abstract

In proof-of-concept studies, the anti-CEA M5A-IR800 conjugate demonstrated rapid and effective near infrared (NIR) imaging of human colon cancer and pancreatic cancer primary and metastatic lesions in mouse models. A limitation observed from these studies is the antibody-dye conjugate’s rapid clearance from the blood due to the increased hydrophobicity of the IR800 dye. This is a bottleneck for clinical applications, requiring high doses to be administered and a short surgical time window for intraoperative imaging. As a result, we developed a new prototype anti-CEA-swPEG-IR800 conjugate, that incorporates a PEGylated sidearm linker to shield or mask the IR800 dye’s hydrophobicity, a novel approach to extend the blood circulation half-life and in doing so increase tumor sensitivity as well as lower normal hepatic uptake. Results of the anti-CEA-swPEG-IR800 in an orthotopic human pancreatic cancer mouse model demonstrated exceptional optical imaging at lower doses, a much longer in vivo half-life enabling increased tumor fluorescence and higher tumor to background ratios. We propose that our novel anti-CEA-swPEG-IR800 is capable of enhanced optical imaging than currently available agents and will become the next generation optical imaging agent for safe and effective intraoperative image-guided surgery in CEA expressing GI cancers.

Paper Details

Date Published: 7 March 2019
PDF: 13 pages
Proc. SPIE 10862, Molecular-Guided Surgery: Molecules, Devices, and Applications V, 108620N (7 March 2019); doi: 10.1117/12.2511771
Show Author Affiliations
Paul J. Yazaki, City of Hope Beckman Research Institute (United States)
Thinzar M. Lwin, Univ. of California, San Diego (United States)
Megan Minnix , City of Hope Beckman Research Institute (United States)
Lin Li, City of Hope Beckman Research Institute (United States)
Anakim Sherman, City of Hope Beckman Research Institute (United States)
Justin Molnar, City of Hope Beckman Research Institute (United States)
Aaron Miller, City of Hope Beckman Research Institute (United States)
Junie Chea, City of Hope Beckman Research Institute (United States)
Erasmus Poku, City of Hope Beckman Research Institute (United States)
Nicole Bowles, City of Hope Beckman Research Institute (United States)
Robert Hoffman, AntiCancer Inc. (United States)
John E. Shively, City of Hope Beckman Research Institute (United States)
Michael Bouvet, Univ. of California, San Diego (United States)
VA San Diego Healthcare System (United States)


Published in SPIE Proceedings Vol. 10862:
Molecular-Guided Surgery: Molecules, Devices, and Applications V
Brian W. Pogue; Sylvain Gioux, Editor(s)

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