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

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.

• Authors: Paul Yazaki, Thinzar Lwin, Megan Minnix, Lin Li, Anakim Sherman, Justin Molnar, Aaron Miller, Paul Frankel, Junie Chea, Erasmus Poku, Nicole Bowles, Robert Hoffman, John Shively, Michael Bouvet
• Journal: Journal of biomedical optics (J Biomed Opt) Vol. 24 Issue 6 Pg. 1-9 (06 2019) ISSN: 1560-2281 [Electronic] United States
• PMID: 31254333 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Antibodies, Neoplasm
• Carcinoembryonic Antigen
• Fluorescent Dyes

Topics

• Animals
• Antibodies, Neoplasm (analysis)
• Carcinoembryonic Antigen (analysis)
• Disease Models, Animal
• Fluorescent Dyes (administration & dosage)
• Mice
• Mice, Nude
• Pancreatic Neoplasms (diagnostic imaging, surgery)
• Spectroscopy, Near-Infrared (methods)
• Surgery, Computer-Assisted (methods)