RT Journal Article
SR Electronic
T1 Use of Fc-Engineered Antibodies as Clearing Agents to Increase Contrast During PET
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1204
OP 1207
DO 10.2967/jnumed.113.136481
VO 55
IS 7
A1 Swiercz, Rafal
A1 Chiguru, Srinivas
A1 Tahmasbi, Amir
A1 Ramezani, Saleh M.
A1 Hao, Guiyang
A1 Challa, Dilip K.
A1 Lewis, Matthew A.
A1 Kulkarni, Padmakar V.
A1 Sun, Xiankai
A1 Ober, Raimund J.
A1 Mason, Ralph P.
A1 Ward, E. Sally
YR 2014
UL http://jnm.snmjournals.org/content/55/7/1204.abstract
AB 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 (124I, 125I) 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.