Use of Fc-Engineered Antibodies as Clearing Agents to Increase Contrast During PET

J Nucl Med. 2014 Jul;55(7):1204-7. doi: 10.2967/jnumed.113.136481. Epub 2014 May 27.


Despite promise for the use of antibodies as molecular imaging agents in PET, their long in vivo half-lives result in poor contrast and radiation damage to normal tissue. This study describes an approach to overcome these limitations.

Methods: Mice bearing human epidermal growth factor receptor type 2 (HER2)-overexpressing tumors were injected with radiolabeled ((124)I, (125)I) HER2-specific antibody (pertuzumab). Pertuzumab injection was followed 8 h later by the delivery of an engineered, antibody-based inhibitor of the receptor, FcRn. Biodistribution analyses and PET were performed at 24 and 48 h after pertuzumab injection.

Results: The delivery of the engineered, antibody-based FcRn inhibitor (or Abdeg, for antibody that enhances IgG degradation) results in improved tumor-to-blood ratios, reduced systemic exposure to radiolabel, and increased contrast during PET.

Conclusion: Abdegs have considerable potential as agents to stringently regulate antibody dynamics in vivo, resulting in increased contrast during molecular imaging with PET.

Keywords: FcRn; PET; breast cancer; engineered antibodies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal, Humanized / immunology
  • Antibodies, Monoclonal, Humanized / metabolism*
  • Antibody Specificity
  • Cell Line, Tumor
  • Female
  • Half-Life
  • Humans
  • Immunoglobulin Fc Fragments / immunology
  • Immunoglobulin Fc Fragments / metabolism*
  • Mice
  • Positron-Emission Tomography*
  • Protein Engineering*
  • Receptor, ErbB-2 / immunology
  • Receptors, Fc / metabolism
  • Signal-To-Noise Ratio*


  • Antibodies, Monoclonal, Humanized
  • Immunoglobulin Fc Fragments
  • Receptors, Fc
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • pertuzumab