Development of a MUC16-Targeted Near-Infrared Fluorescent Antibody Conjugate for Intraoperative Imaging of Pancreatic Cancer

Mol Cancer Ther. 2020 Aug;19(8):1670-1681. doi: 10.1158/1535-7163.MCT-20-0033. Epub 2020 May 13.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / chemistry*
  • Antibodies, Monoclonal / immunology
  • CA-125 Antigen / immunology*
  • Female
  • Fluorescent Dyes / chemistry*
  • Humans
  • Immunoconjugates / administration & dosage*
  • Immunoconjugates / pharmacokinetics
  • Indoles / chemistry*
  • Membrane Proteins / immunology*
  • Mice
  • Pancreatic Neoplasms / diagnostic imaging
  • Pancreatic Neoplasms / pathology
  • Pancreatic Neoplasms / surgery*
  • Spectroscopy, Near-Infrared / methods*
  • Surgery, Computer-Assisted / methods
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • Antibodies, Monoclonal
  • CA-125 Antigen
  • Fluorescent Dyes
  • IRDye800
  • Immunoconjugates
  • Indoles
  • MUC16 protein, human
  • Membrane Proteins