Rafal Swiercz1, Srinivas Chiguru2, Amir Tahmasbi3, Saleh M Ramezani2, Guiyang Hao2, Dilip K Challa1, Matthew A Lewis2, Padmakar V Kulkarni2, Xiankai Sun2, Raimund J Ober4, Ralph P Mason2, E Sally Ward5. 1. Department of Immunology, University of Texas Southwestern Medical Center, Dallas, Texas. 2. Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Texas; and. 3. Department of Electrical Engineering, University of Texas at Dallas, Richardson, Texas. 4. Department of Immunology, University of Texas Southwestern Medical Center, Dallas, Texas Department of Electrical Engineering, University of Texas at Dallas, Richardson, Texas. 5. Department of Immunology, University of Texas Southwestern Medical Center, Dallas, Texas Sally.Ward@utsouthwestern.edu.
Abstract
UNLABELLED: 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.
UNLABELLED: 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.
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