RT Journal Article
SR Electronic
T1 Imaging of Platelet-Derived Growth Factor Receptor β Expression in Glioblastoma Xenografts Using Affibody Molecule <sup>111</sup>In-DOTA-Z09591
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 294
OP 300
DO 10.2967/jnumed.113.121814
VO 55
IS 2
A1 Vladimir Tolmachev
A1 Zohreh Varasteh
A1 Hadis Honarvar
A1 Seyed Jalal Hosseinimehr
A1 Olof Eriksson
A1 Per Jonasson
A1 Fredrik Y. Frejd
A1 Lars Abrahmsen
A1 Anna Orlova
YR 2014
UL http://jnm.snmjournals.org/content/55/2/294.abstract
AB The overexpression and excessive signaling of platelet-derived growth factor receptor β (PDGFRβ) has been detected in cancers, atherosclerosis, and a variety of fibrotic diseases. Radionuclide in vivo visualization of PDGFRβ expression might help to select PDGFRβ targeting treatment for these diseases. The goal of this study was to evaluate the feasibility of in vivo radionuclide imaging of PDGFRβ expression using an Affibody molecule, a small nonimmunoglobulin affinity protein. Methods: The PDGFRβ-binding Z09591 Affibody molecule was site-specifically conjugated with a maleimido derivative of DOTA and labeled with 111In. Targeting of the PDGFRβ-expressing U-87 MG glioblastoma cell line using 111In-DOTA-Z09591 was evaluated in vitro and in vivo. Results: DOTA-Z09591 was stably labeled with 111In with preserved specific binding to PDGFRβ-expressing cells in vitro. The dissociation constant for 111In-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 111In-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 PDGFRβ-specific. U-87 MG xenografts were clearly visualized using small-animal SPECT/CT at 3 h after injection. Conclusion: This study demonstrates the feasibility of in vivo visualization of PDGFRβ-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.