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

作者：Swiercz Rafal; Chiguru Srinivas; Tahma**i Amir; Ramezani Saleh M; Hao Guiyang; Challa Dilip K; Lewis Matthew A; Kulkarni Padmakar V; Sun Xiankai; Ober Raimund J; Mason Ralph P; Ward E Sally^*

来源：Journal of Nuclear Medicine, 2014, 55(7): 1204-1207.

DOI：10.2967/jnumed.113.136481

• engineered antibodies
• PET
• breast cancer
• FcRn

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 (I-124, I-125) 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 arid 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.

• 出版日期2014-7