Improved antibody-guided surgery with a near-infrared dye on a PEGylated linker for CEA-positive tumors

Paul J. Yazaki; Thinzar M. Lwin; Megan Minnix; Lin Li; Anakim Sherman; Justin Molnar; Aaron Miller; Paul Frankel; Junie Chea; Erasmus Poku; Nicole Bowles; Robert M. Hoffman; John E. Shively; Michael Bouvet

doi:10.1117/1.JBO.24.6.066012

28 June 2019 Improved antibody-guided surgery with a near-infrared dye on a PEGylated linker for CEA-positive tumors

Paul J. Yazaki, Thinzar M. Lwin, Megan Minnix, Lin Li, Anakim Sherman, Justin Molnar, Aaron Miller, Paul Frankel, Junie Chea, Erasmus Poku, Nicole Bowles, Robert M. Hoffman, John E. Shively, Michael Bouvet

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Journal of Biomedical Optics, Vol. 24, Issue 6, 066012 (June 2019). https://doi.org/10.1117/1.JBO.24.6.066012

Abstract

Real-time intraoperative image-guided cancer surgery promises to improve oncologic outcomes. Tumor-specific antibodies conjugated with near-infrared (NIR) fluorophores have demonstrated the potential to enhance visualization of solid tumor margins and metastatic disease; however, multiple challenges remain, including improvement in probe development for clinical utility. We have developed an NIR-IR800 dye on a PEGylated linker (sidewinder) conjugated to the humanized anti-carcinoembryonic antigen (CEA) antibody (M5A) with extended in vivo serum and tumor persistence. The anti-CEA M5A-sidewinder has a high dye-to-antibody ratio (average of 7 per antibody) that allows, in an orthotopic implanted human pancreatic cancer mouse model increased tumor fluorescence, higher tumor-to-background ratio and extends the surgical scheduling window compared to current antibody dye conjugates. These preclinical results demonstrate the potential of this probe for fluorescence-guided surgery of CEA-positive gastrointestinal cancers.

CC BY: © The Authors. Published by SPIE under a Creative Commons Attribution 4.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.

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Paul J. Yazaki, Thinzar M. Lwin, Megan Minnix, Lin Li, Anakim Sherman, Justin Molnar, Aaron Miller, Paul Frankel, Junie Chea, Erasmus Poku, Nicole Bowles, Robert M. Hoffman, John E. Shively, and Michael Bouvet "Improved antibody-guided surgery with a near-infrared dye on a PEGylated linker for CEA-positive tumors," Journal of Biomedical Optics 24(6), 066012 (28 June 2019). https://doi.org/10.1117/1.JBO.24.6.066012

Received: 30 January 2019; Accepted: 4 June 2019; Published: 28 June 2019

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