Get access

Antibody-functionalized nanoparticles for imaging cancer: influence of conjugation to gold nanoparticles on the biodistribution of 89Zr-labeled cetuximab in mice

Authors

  • Linda Karmani,

    1. Biomedical Magnetic Resonance Group, Louvain Drug Research Institute, Université Catholique de Louvain, Brussels, Belgium
    Search for more papers by this author
  • Daniel Labar,

    1. Center for Molecular Imaging, Radiotherapy and Oncology, Institute of Experimental and Clinical Research, Université Catholique de Louvain, Brussels, Belgium
    Search for more papers by this author
  • Vanessa Valembois,

    1. Research Center for the Physics of Matter and Radiation, University of Namur, Namur Research Institute for Life Sciences, Namur, Belgium
    Search for more papers by this author
  • Virginie Bouchat,

    1. Research Center for the Physics of Matter and Radiation, University of Namur, Namur Research Institute for Life Sciences, Namur, Belgium
    Search for more papers by this author
  • Praveen Ganesh Nagaswaran,

    1. Namur Research College and Department of Chemistry, University of Namur, Namur, Belgium
    Search for more papers by this author
  • Anne Bol,

    1. Center for Molecular Imaging, Radiotherapy and Oncology, Institute of Experimental and Clinical Research, Université Catholique de Louvain, Brussels, Belgium
    Search for more papers by this author
  • Jacques Gillart,

    1. Center for Molecular Imaging, Radiotherapy and Oncology, Institute of Experimental and Clinical Research, Université Catholique de Louvain, Brussels, Belgium
    Search for more papers by this author
  • Philippe Levêque,

    1. Biomedical Magnetic Resonance Group, Louvain Drug Research Institute, Université Catholique de Louvain, Brussels, Belgium
    Search for more papers by this author
  • Caroline Bouzin,

    1. Pole of Pharmacology and Therapeutics, Institute of Experimental and Clinical Research, Université Catholique de Louvain, Brussels, Belgium
    Search for more papers by this author
  • Davide Bonifazi,

    1. Namur Research College and Department of Chemistry, University of Namur, Namur, Belgium
    Search for more papers by this author
  • Carine Michiels,

    1. Unité de Recherche en Biologie Cellulaire, University of Namur, Namur Research Institute for Life Sciences, Namur, Belgium
    Search for more papers by this author
  • Olivier Feron,

    1. Pole of Pharmacology and Therapeutics, Institute of Experimental and Clinical Research, Université Catholique de Louvain, Brussels, Belgium
    Search for more papers by this author
  • Vincent Grégoire,

    1. Center for Molecular Imaging, Radiotherapy and Oncology, Institute of Experimental and Clinical Research, Université Catholique de Louvain, Brussels, Belgium
    Search for more papers by this author
  • Stéphane Lucas,

    1. Research Center for the Physics of Matter and Radiation, University of Namur, Namur Research Institute for Life Sciences, Namur, Belgium
    Search for more papers by this author
  • Thierry Vander Borght,

    1. Center for Molecular Imaging, Radiotherapy and Oncology, Institute of Experimental and Clinical Research, Université Catholique de Louvain, Brussels, Belgium
    Search for more papers by this author
  • Bernard Gallez

    Corresponding author
    • Biomedical Magnetic Resonance Group, Louvain Drug Research Institute, Université Catholique de Louvain, Brussels, Belgium
    Search for more papers by this author

Correspondence to: B. Gallez, Biomedical Magnetic Resonance Group, Louvain Drug Research Institute, Université Catholique de Louvain, Avenue Mounier 73, 1200 Brussels, Belgium. E-mail: Bernard.Gallez@uclouvain.be

Abstract

Antibody-labeled gold nanoparticles represent a promising novel tool regarding cancer imaging and therapy. Nevertheless, the characterization of biodistribution of such immunonanocarriers has been poorly documented. In this study, the biodistribution of 89Zr-labeled cetuximab before and after the coupling reaction to gold nanoparticles (AuNPs) was compared and the quantitative imaging performance of 89Zr immuno-PET was evaluated. Cetuximab was functionalized with the desferal moiety and labeled with 89Zr (89Zr–Df–Bz–NCS–cetuximab). AuNPs with a mean diameter of 5 nm were synthesized according a new method developed in the laboratory, and conjugated to 89Zr–Df–Bz–NCS–cetuximab using carbodiimide chemistry (AuNPs–PPAA–cetuximab–89Zr). The two tracers were injected in A431 xenograft-bearing mice. Tumor and liver uptakes were assessed at different times after injection using quantitative PET imaging. The in vivo specificity of the binding was investigated using a saturating dose of unlabeled cetuximab. Radiolabeled cetuximab was conjugated to AuNPs with a coupling reaction yield >75%. All conjugates were stable in vitro and to a lesser extent in plasma. In vivo distribution studies revealed no significant difference in tumor uptake for cetuximab conjugated to nanoparticles up to 72 h after injection, compared with unconjugated cetuximab. Immuno-PET studies showed that AuNPs–PPAA–cetuximab–89Zr provided high tumor-to-background ratio. The liver uptake of AuNPs–PPAA–cetuximab–89Zr was higher, compared with 89Zr–Df–Bz–NCS–cetuximab. In vivo blocking experiments demonstrated selective tumor targeting after coupling reaction. This study showed that the conjugation of AuNPs to cetuximab did not affect its tumor accumulation and that the efficacy of EGFR-targeted nanoparticles was unaltered. The 89Zr-labeled cetuximab-targeted gold nanoparticles could be a valuable tool for theranostic purposes. Copyright © 2013 John Wiley & Sons, Ltd.

Ancillary