Use of Fc-engineered antibodies as clearing agents to increase contrast during PET

Rafal Swiercz, Srinivas Chiguru, Amir Tahmasbi, Saleh M. Ramezani, Guiyang Hao, Dilip K. Challa, Matthew A. Lewis, Padmakar V. Kulkarni, Xiankai Sun, Raimund J. Ober, Ralph P. Mason, E. Sally Ward

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

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 (124I, 125I) 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. COPYRIGHT

Original languageEnglish (US)
Pages (from-to)1204-1207
Number of pages4
JournalJournal of Nuclear Medicine
Volume55
Issue number7
DOIs
StatePublished - Jul 1 2014

Keywords

  • Breast cancer
  • Engineered antibodies
  • FcRn
  • PET

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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    Swiercz, R., Chiguru, S., Tahmasbi, A., Ramezani, S. M., Hao, G., Challa, D. K., Lewis, M. A., Kulkarni, P. V., Sun, X., Ober, R. J., Mason, R. P., & Ward, E. S. (2014). Use of Fc-engineered antibodies as clearing agents to increase contrast during PET. Journal of Nuclear Medicine, 55(7), 1204-1207. https://doi.org/10.2967/jnumed.113.136481