title: Use of Fc-Engineered Antibodies as Clearing Agents to Increase Contrast During PET.
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 ((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.
  
  
  CONCLUSIONS
  Abdegs have considerable potential as agents to stringently regulate antibody dynamics in vivo, resulting in increased contrast during molecular imaging with PET.
authors.affiliation: Department of Immunology, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Rafal
authors.initials: R
authors.lastname: Swiercz
authors.affiliation: Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Texas; and.
authors.forename: Srinivas
authors.initials: S
authors.lastname: Chiguru
authors.affiliation: Department of Electrical Engineering, University of Texas at Dallas, Richardson, Texas.
authors.forename: Amir
authors.initials: A
authors.lastname: Tahmasbi
authors.affiliation: Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Texas; and.
authors.forename: Saleh M
authors.initials: SM
authors.lastname: Ramezani
authors.affiliation: Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Texas; and.
authors.forename: Guiyang
authors.initials: G
authors.lastname: Hao
authors.affiliation: Department of Immunology, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Dilip K
authors.initials: DK
authors.lastname: Challa
authors.affiliation: Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Texas; and.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Lewis
authors.affiliation: Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Texas; and.
authors.forename: Padmakar V
authors.initials: PV
authors.lastname: Kulkarni
authors.affiliation: Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Texas; and.
authors.forename: Xiankai
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Immunology, University of Texas Southwestern Medical Center, Dallas, Texas Department of Electrical Engineering, University of Texas at Dallas, Richardson, Texas.
authors.forename: Raimund J
authors.initials: RJ
authors.lastname: Ober
authors.affiliation: Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Texas; and.
authors.forename: Ralph P
authors.initials: RP
authors.lastname: Mason
authors.affiliation: Department of Immunology, University of Texas Southwestern Medical Center, Dallas, Texas Sally.Ward@utsouthwestern.edu.
authors.forename: E Sally
authors.initials: ES
authors.lastname: Ward
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000276:immunology / Q000378:metabolism*; D000918:Antibody Specificity; D045744:Cell Line, Tumor; D005260:Female; D006207:Half-Life; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D049268:Positron-Emission Tomography; D015202:Protein Engineering; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology; D011961:Receptors, Fc / Q000378:metabolism; D059629:Signal-To-Noise Ratio
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D007141:Immunoglobulin Fc Fragments; D018719:Erb-b2 Receptor Tyrosine Kinases; D011961:Receptors, Fc; C508053:ERBB2 protein, human; C485206:pertuzumab
keywords: FcRn; PET; breast cancer; engineered antibodies