Preclinical Evaluation of an Anti-Nectin-4 ImmunoPET Reagent in Tumor-Bearing Mice and Biodistribution Studies in Cynomolgus Monkeys

Mol Imaging Biol. 2016 Oct;18(5):768-75. doi: 10.1007/s11307-016-0953-x.

Abstract

Purpose: Nectin-4 is selectively overexpressed in a variety of cancers and is currently under clinical investigation as a therapeutic target. A monoclonal antibody against nectin-4 (AGS-22M6) was evaluated as an Immuno-positron emission tomography (ImmunoPET) reagent. Its ability to assay nectin-4 expression as well as detect nectin-4 positive tumors in the liver and bone was evaluated using mouse models.

Procedures: The biodistribution of [(89)Zr]AGS-22M6 was evaluated in mice bearing tumors with varying levels of nectin-4 expression. An isogenic breast cancer tumor line was used to model metastatic liver and bone disease in mice. The biodistribution of [(18)F]AGS-22M6 in cynomolgus monkeys was evaluated.

Results: A positive correlation was demonstrated between tumor nectin-4 expression and [(89)Zr]AGS-22M6 uptake. Tumors in the liver and bone were detected and differentiated based on nectin-4 expression. [(18)F]AGS-22M6 showed limited uptake in cynomolgus monkey tissues.

Conclusions: [(89)Zr]AGS-22M6 is a promising ImmunoPET reagent that can assay nectin-4 expression in both primary and metastatic lesions.

Keywords: ImmunoPET; Liver imaging; Nectin-4; Zr-89 PET.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology*
  • Bone Neoplasms / secondary
  • Cell Adhesion Molecules / immunology*
  • Cell Line, Tumor
  • Humans
  • Immunohistochemistry
  • Indicators and Reagents
  • Liver Neoplasms / secondary
  • Macaca fascicularis
  • Mice
  • Nectins
  • Positron-Emission Tomography / methods*
  • Tissue Distribution
  • Xenograft Model Antitumor Assays*
  • Zirconium / chemistry

Substances

  • Antibodies, Monoclonal
  • Cell Adhesion Molecules
  • Indicators and Reagents
  • Nectins
  • Zirconium