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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.

SUBMITTER: Yazaki P 

PROVIDER: S-EPMC6978469 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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

Yazaki Paul P   Lwin Thinzar T   Minnix Megan M   Li Lin L   Sherman Anakim A   Molnar Justin J   Miller Aaron A   Frankel Paul P   Chea Junie J   Poku Erasmus E   Bowles Nicole N   Hoffman Robert R   Shively John J   Bouvet Michael M  

Journal of biomedical optics 20190601 6


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 antige  ...[more]

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