Positron Emission Tomography Imaging of Platelet-Derived Growth Factor Receptor β in Colorectal Tumor Xenograft Using Zirconium-89 Labeled Dimeric Affibody Molecule
| Autor: | Fang Xie, Ze Tao, Xiaofeng Lu, Rong Tian, Xiaoai Wu, Hao Yang, Qiuxiao Shi, Haoxing Wu, Yue Chen, Yu Tang, Huawei Cai, Nan Liu, Yuanyou Yang, Lin Li, Lihong Chen |
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| Rok vydání: | 2019 |
| Předmět: |
Biodistribution
BALB 3T3 Cells Mice Nude Pharmaceutical Science Pilot Projects 02 engineering and technology Deferoxamine 030226 pharmacology & pharmacy Flow cytometry Receptor Platelet-Derived Growth Factor beta Mice 03 medical and health sciences 0302 clinical medicine Growth factor receptor In vivo Cell Line Tumor Positron Emission Tomography Computed Tomography Drug Discovery medicine Animals Humans Tissue Distribution Radioisotopes medicine.diagnostic_test biology Chemistry Antibodies Monoclonal 021001 nanoscience & nanotechnology Xenograft Model Antitumor Assays Positron emission tomography Cancer cell biology.protein Cancer research Molecular Medicine Affibody molecule Zirconium Colorectal Neoplasms Pericytes 0210 nano-technology Platelet-derived growth factor receptor |
| Zdroj: | Molecular Pharmaceutics. 16:1950-1957 |
| ISSN: | 1543-8392 1543-8384 |
| Popis: | Platelet-derived growth factor receptor β (PDGFRβ) is overexpressed in a variety of malignant cancers, plays a critical role in tumor angiogenesis, and has been proven as a valuable target for cancer treatment. In this pilot study, a dimeric affibody molecule, ZPDGFRβ, was prepared and radiolabeled with positron emission radionuclide zirconium-89 for PET imaging of colorectal tumors by targeting PDGFRβ expression in vivo. The PDGFRβ-binding capability of dimeric affibody was evaluated by flow cytometry, immunofluorescent staining, and whole-body optical imaging. Then, ZPDGFRβ was 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. Dimeric ZPDGFRβ affibody had specifically higher binding capability with PDGFRβ expressing pericytes rather than LS-174T cancer cells, and well colocalized 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 PDGF-β ligands ( P < 0.05) in vitro. Biodistribution indicated that tumor uptake of 89Zr-DFO-ZPDGFRβ reached the peak of 6.93 ± 0.64%ID/g, and the tumor-to-blood ratio was 5.5 ± 0.6 at 2 h post-injection. LS-174T xenografts were clearly visualized by microPET/CT imaging through 1 to 4 h post-injection of 89Zr-DFO-ZPDGFRβ affibody conjugate. In conclusion, the 89Zr-DFO-ZPDGFRβ conjugate demonstrated specific and high binding ability with colorectal tumor, which indicated its use as a potential radiopharmaceutical for diagnostic imaging of tumor associate vasculatures with PET/CT. |
| Databáze: | OpenAIRE |
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