Development of a MUC16-targeted near-infrared fluorescent antibody conjugate for intraoperative imaging of pancreatic cancer

Madeline T. Olson, Nicholas E. Wojtynek, Geoffrey A. Talmon, Thomas C. Caffrey, Prakash Radhakrishnan, Quan P. Ly, Michael A. Hollingsworth, Aaron M. Mohs

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Surgical resection is currently the only potentially curative option for patients with pancreatic cancer. However, the 5-year survival rate after resection is only 25%, due in part to high rates of R1 resections, in which cells are left behind at the surgical margin, resulting in disease recurrence. Fluorescence-guided surgery (FGS) has emerged as a method to reduce incomplete resections and improve intraoperative assessment of cancer. Mucin-16 (MUC16), a protein biomarker highly overexpressed in pancreatic cancer, is a potential target for FGS. In this study, we developed a fluorescent MUC16-targeted antibody probe, AR9.6-IRDye800, for image-guided resection of pancreatic cancer. We demonstrated the efficacy of this probe to bind human pancreatic cancer cell lines in vitro and in vivo. In an orthotopic xenograft model, AR9.6-IRDye800 exhibited superior fluorescence enhancement of tumors and lower signal in critical background organs in comparison to a nonspecific IgG control. The results of this study suggest that AR9.6-IRDye800 has potential for success as a probe for FGS in pancreatic cancer patients, and MUC16 is a feasible target for intraoperative imaging.

Original languageEnglish (US)
Pages (from-to)1670-1681
Number of pages12
JournalMolecular cancer therapeutics
Volume19
Issue number8
DOIs
StatePublished - Aug 1 2020

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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