TY - JOUR T1 - Use of Fc-Engineered Antibodies as Clearing Agents to Increase Contrast During PET JF - Journal of Nuclear Medicine JO - J Nucl Med DO - 10.2967/jnumed.113.136481 SP - jnumed.113.136481 AU - Rafal Swiercz AU - Srinivas Chiguru AU - Amir Tahmasbi AU - Saleh M. Ramezani AU - Guiyang Hao AU - Dilip K. Challa AU - Matthew A. Lewis AU - Padmakar V. Kulkarni AU - Xiankai Sun AU - Raimund J. Ober AU - Ralph P. Mason AU - E. Sally Ward Y1 - 2014/07/01 UR - http://jnm.snmjournals.org/content/early/2014/05/22/jnumed.113.136481.abstract N2 - 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. ER -