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PET Imaging of Platelet-Derived Growth Factor Receptor β in Colorectal Tumor Xenograft using Zirconium-89 Labeled Dimeric Affibody Molecule.

08:00 EDT 15th April 2019 | BioPortfolio

Summary of "PET Imaging of Platelet-Derived Growth Factor Receptor β in Colorectal Tumor Xenograft using Zirconium-89 Labeled Dimeric Affibody Molecule."

Platelet-derived growth factor receptor β (PDGFRβ) is overexpressed in a variety of malignant cancers and plays 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 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 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 of colorectal tumor, which indicated as a potential radiopharmaceutical for diagnostic imaging of tumor associate vasculatures with PET/CT.

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This article was published in the following journal.

Name: Molecular pharmaceutics
ISSN: 1543-8392
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Medical and Biotech [MESH] Definitions

Specific receptors on cell membranes that react with PLATELET-DERIVED GROWTH FACTOR, its analogs, or antagonists. The alpha PDGF receptor (RECEPTOR, PLATELET-DERIVED GROWTH FACTOR ALPHA) and the beta PDGF receptor (RECEPTOR, PLATELET-DERIVED GROWTH FACTOR BETA) are the two principle types of PDGF receptors. Activation of the protein-tyrosine kinase activity of the receptors occurs by ligand-induced dimerization or heterodimerization of PDGF receptor types.

A PDGF receptor that binds specifically to the PDGF-B chain. It contains a protein-tyrosine kinase activity that is involved in SIGNAL TRANSDUCTION.

The original member of the family of endothelial cell growth factors referred to as VASCULAR ENDOTHELIAL GROWTH FACTORS. Vascular endothelial growth factor-A was originally isolated from tumor cells and referred to as "tumor angiogenesis factor" and "vascular permeability factor". Although expressed at high levels in certain tumor-derived cells it is produced by a wide variety of cell types. In addition to stimulating vascular growth and vascular permeability it may play a role in stimulating VASODILATION via NITRIC OXIDE-dependent pathways. Alternative splicing of the mRNA for vascular endothelial growth factor A results in several isoforms of the protein being produced.

A signal transducing adaptor protein that links extracellular signals to the MAP KINASE SIGNALING SYSTEM. Grb2 associates with activated EPIDERMAL GROWTH FACTOR RECEPTOR and PLATELET-DERIVED GROWTH FACTOR RECEPTORS via its SH2 DOMAIN. It also binds to and translocates the SON OF SEVENLESS PROTEINS through its SH3 DOMAINS to activate PROTO-ONCOGENE PROTEIN P21(RAS).

A fibroblast growth factor receptor that is found in two isoforms. One receptor isoform is found in the MESENCHYME and is activated by FIBROBLAST GROWTH FACTOR 2. A second isoform of fibroblast growth factor receptor 2 is found mainly in EPITHELIAL CELLS and is activated by FIBROBLAST GROWTH FACTOR 7 and FIBROBLAST GROWTH FACTOR 10. Mutation of the gene for fibroblast growth factor receptor 2 can result in APERT SYNDROME.

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