Journal
JOURNAL OF NUCLEAR MEDICINE
Volume 55, Issue 7, Pages 1204-1207Publisher
SOC NUCLEAR MEDICINE INC
DOI: 10.2967/jnumed.113.136481
Keywords
engineered antibodies; PET; breast cancer; FcRn
Funding
- Cancer Prevention and Research Institute of Texas (CPRIT) [RP 110070, RP 110441]
- Simmons Cancer Center support grant [5P30 CA 142543]
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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.
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