Imaging of Platelet-Derived Growth Factor Receptor [Beta] Expression in Glioblastoma Xenografts Using Affibody Molecule ^sup 111^In-DOTA-Z09591

The overexpression and excessive signaling of platelet-derived growth factor receptor ... (PDGFR...) has been detected in cancers, atherosclerosis, and a variety of fibrotic diseases. Radionuclide in vivo visualization of PDGFR... expression might help to select PDGFR... targeting treatment for these diseases. The goal of this study was to evaluate the feasibility of in vivo radionuclide imaging of PDGFR... expression using an Affibody molecule, a small nonimmunoglobulin affinity protein. The PDGFR...-binding Z09591 Affibody molecule was site-specifically conjugated with a maleimido derivative of DOTA and labeled with ^sup 111^In. Targeting of the PDGFR...-expressing U-87 MG glioblastoma cell line using ^sup 111^In-DOTA-Z09591 was evaluated in vitro and in vivo. DOTA-Z09591 was stably labeled with ^sup 111^In with preserved specific binding to PDGFR...-expressing cells in vitro. The dissociation constant for ^sup 111^In-DOTA-Z09591 binding to U-87 MG cells was determined to be 92 ± 10 pM. In mice bearing U-87 MG xenografts, the tumor uptake of ^sup 111^In-DOTA-Z09591 was 7.2 ± 2.4 percentage injected dose per gram and the tumor-to-blood ratio was 28 ± 14 at 2 h after injection. In vivo receptor saturation experiments demonstrated that targeting of U-87 MG xenografts in mice was PDGFR...-specific. U-87 MG xenografts were clearly visualized using small-animal SPECT/CT at 3 h after injection. This study demonstrates the feasibility of in vivo visualization of PDGFR...-expressing xenografts using an Affibody molecule. Further development of radiolabeled Affibody molecules might provide a useful clinical imaging tool for PDGFRβ expression during various pathologic conditions. (ProQuest: ... denotes formulae/symbols omitted.)