PT  - JOURNAL ARTICLE
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
TI  - Use of Fc-Engineered Antibodies as Clearing Agents to Increase Contrast During PET
AID  - 10.2967/jnumed.113.136481
DP  - 2014 Jul 01
TA  - Journal of Nuclear Medicine
PG  - jnumed.113.136481
4099  - http://jnm.snmjournals.org/content/early/2014/05/22/jnumed.113.136481.short
4100  - http://jnm.snmjournals.org/content/early/2014/05/22/jnumed.113.136481.full
AB  - 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.