PloS one, 2018-06, Vol.13 (6), p.e0199024-e0199024
2018
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- Autor(en) / Beteiligte
- Titel
- Imaging c-Met expression using 18F-labeled binding peptide in human cancer xenografts
- Ist Teil von
- PloS one, 2018-06, Vol.13 (6), p.e0199024-e0199024
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2018
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- c-Met is a receptor tyrosine kinase shown inappropriate expression and actively involved in progression and metastasis in most types of human cancer. Development of c-Met-targeted imaging and therapeutic agents would be extremely useful. Previous studies reported that c-Met-binding peptide (Met-pep1, YLFSVHWPPLKA) specifically targets c-Met receptor. Here, we evaluated 18F-labeled Met-pep1 for PET imaging of c-Met positive tumor in human head and neck squamous cell carcinoma (HNSCC) xenografted mice. c-Met-binding peptide, Met-pep1, was synthesized and labeled with 4-nitrophenyl [18F]-2-fluoropropionate ([18F]-NPFP) ([18F]FP-Met-pep1). The cell uptake, internalization and efflux of [18F]FP-Met-pep1 were assessed in UM-SCC-22B cells. In vivo pharmacokinetics, blocking and biodistribution of the radiotracers were investigated in tumor-bearing nude mice by microPET imaging. The radiolabeling yield for [18F]FP-Met-pep1 was over 55% with 97% purity. [18F]FP-Met-pep1 showed high tumor uptake in UM-SCC-22B tumor-bearing mice with clear visualization. The specificity of the imaging tracer was confirmed by significantly decreased tumor uptake after co-administration of unlabeled Met-pep1 peptides. Prominent uptake and rapid excretion of [18F]FP-Met-pep1 was also observed in the kidney, suggesting this tracer is mainly excreted through the renal-urinary routes. Ex vivo biodistribution showed similar results that were consistent with microPET imaging data. These results suggest that 18F-labeled c-Met peptide may potentially be used for imaging c-Met positive HNSCC cancer in vivo and for c-Met-targeted cancer therapy.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0199024Titel-ID: cdi_plos_journals_2054046842
- Format
- –
- Schlagworte
- Animals, Apoptosis, Binding, Binding proteins, Biology and Life Sciences, c-Met protein, Cancer, Carcinoma, Squamous Cell - diagnostic imaging, Carcinoma, Squamous Cell - metabolism, Carcinoma, Squamous Cell - pathology, Cell Proliferation, Chemical compounds, Diagnosis, Efflux, Excretion, Fluorine isotopes, Fluorine Radioisotopes, Gene expression, Gene Expression Regulation, Neoplastic, Genetic aspects, Growth factors, Head, Head & neck cancer, Head and neck cancer, Head and Neck Neoplasms - diagnostic imaging, Head and Neck Neoplasms - metabolism, Head and Neck Neoplasms - pathology, Hospitals, Humans, Imaging, In vivo methods and tests, Internalization, Iodine, Kidneys, Male, Medical imaging, Medicine and Health Sciences, Metastases, Mice, Mice, Nude, Nuclear medicine, Peptide Fragments - metabolism, Peptides, Pharmacokinetics, Pharmacology, Physical Sciences, Positron emission, Positron-Emission Tomography - methods, Prostate, Prostheses, Protein-tyrosine kinase receptors, Proto-Oncogene Proteins c-met - metabolism, Radioactive tracers, Radioisotopes, Radiolabelling, Research and Analysis Methods, Risk factors, Sensors, Squamous cell carcinoma, Tomography, Tumor Cells, Cultured, Tumors, Tyrosine, Visualization, Xenograft Model Antitumor Assays, Xenografts, Xenotransplantation