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J Nucl Med. 2014 Jul;55(7):1204-7. doi: 10.2967/jnumed.113.136481. Epub 2014 May 27.

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

Author information

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

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.

KEYWORDS:

FcRn; PET; breast cancer; engineered antibodies

PMID:
24868106
PMCID:
PMC4519079
DOI:
10.2967/jnumed.113.136481
[Indexed for MEDLINE]
Free PMC Article
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