ImmunoPET Imaging of Platelet-Derived Growth Factor Receptor β in Colorectal Tumor Xenograft using Zirconium-89 Radiolabeled Dimeric Affibody Molecule

Background: Platelet-derived growth factor receptor β (PDGFRβ) is overexpressed in a variety of malignant cancers and plays critical role in tumoral angiogenesis, and has been proven as valuable target for cancer treatment. In this study, a dimeric affibody molecule, ZPDGFRβ, was prepared and radiolabeled with positron emission radionuclide zirconium-89 (89Zr, T1/2=78.4 h, mean Eβ+= 0.389 MeV) for immunoPET imaging of colorectal tumors by targeting PDGFRβ expression in vivo. Materials and Methods: The PDGFRβ-binding capability of dimeric affibody was evaluated by flow cytometry, immunofluorescent staining and whole-body optical imaging. Then, ZPDGFRβ was site-specifically conjugated with DFO-Bn-NCS and radiolabeled with 89Zr. Targeted binding capability of 89Zr-DFO-ZPDGFRβ to PDGFRβ expressing cells was investigated by cellular assay in vitro and microPET/CT imaging in vivo. Results: Dimeric ZPDGFRβ affibody had specifically high binding capability with PDGFRβ expressing pericytes rather than LS-174T cancer cells, and well co-localized with tumor neovasculature by flow cytometry and immunofluorescent assay. ZPDGFRβ was successfully labeled with 89Zr by DFO chelating with yield of 94.1 ± 3.53 %. 89Zr-DFO-ZPDGFRβ indicated preserved specific binding ability with PDGFRβ expressing cells and effective inhibiting capability to PDGFRβ ligands (P