Shima Shahsavari1,2, Zahra Shaghaghi1,3, Seyed Mohammad Abedi4, Seyed Jalal Hosseinimehr1. 1. Faculty of Pharmacy, Department of Radiopharmacy, Mazandaran University of Medical Sciences, Sari, Iran. 2. Faculty of Pharmacy, Student Research Committee, Mazandaran University of Medical Sciences, Sari, Iran. 3. Department of Nuclear Medicine and Molecular Imaging, Clinical Development Research Unit of Farshchian Heart Center, Hamadan University of Medical Sciences, Hamadan, Iran. 4. Faculty of Medicine, Department of Radiology, Mazandaran University of Medical Sciences, Sari, Iran.
Abstract
Purpose: Early and accurate imaging of glioblastoma is of great value in staging, metastatic detection, treatment management and prognosis. The human epidermal growth factor receptor 2 (HER2) plays an essential role in the tumorigenesis and tumor progression in cancer. The aim of this study was to develop HER2-targeted peptide for glioma tumor imaging.Material and methods: HYNIC-(Ser)3-LTVPWY peptide was labeled with technetium-99m in presence of EDDA/tricine mixture as co-ligands. 99mTc-HYNIC-(Ser)3-LTVPWY peptide was assessed for cellular specific binding and receptor-binding affinity. The biodistribution study and tumor imaging were conducted in nude mice bearing U-87 MG glioma xenografts. Results: The in vitro blocking study demonstrated specific binding of 99mTc-HYNIC-(Ser)3-LTVPWY in cultured U-87 MG cells with a KD of 9.7 ± 2.0 nM. Biodistribution study revealed tumor to blood and tumor to muscle ratios were about 5.55 and 6.65 respectively after 1 h injection of radiolabeled peptide. Blocking study with non-labeled counterpart indicated a significant reduction (68%) in tumor uptake of 99mTc-HYNIC-(Ser)3-LTVPWY that is indicated the tumor specificity of the radiolabeled peptide on glioblastoma. Gamma planar imaging revealed that the U-87 MG tumor was clearly visualized at 1 h. Conclusion: The results of this study showed that the 99mTc-HYNIC-(Ser)3-LTVPWY peptide specifically accumulates in glioma and is, therefore, a promising probe for the diagnosis of glioma.
Purpose: Early and accurate imaging of glioblastoma is of great value in staging, metastatic detection, treatment management and prognosis. The humanepidermal growth factor receptor 2 (HER2) plays an essential role in the tumorigenesis and tumor progression in cancer. The aim of this study was to develop HER2-targeted peptide for glioma tumor imaging.Material and methods: HYNIC-(Ser)3-LTVPWY peptide was labeled with technetium-99m in presence of EDDA/tricine mixture as co-ligands. 99mTc-HYNIC-(Ser)3-LTVPWY peptide was assessed for cellular specific binding and receptor-binding affinity. The biodistribution study and tumor imaging were conducted in nude mice bearing U-87 MG glioma xenografts. Results: The in vitro blocking study demonstrated specific binding of 99mTc-HYNIC-(Ser)3-LTVPWY in cultured U-87 MG cells with a KD of 9.7 ± 2.0 nM. Biodistribution study revealed tumor to blood and tumor to muscle ratios were about 5.55 and 6.65 respectively after 1 h injection of radiolabeled peptide. Blocking study with non-labeled counterpart indicated a significant reduction (68%) in tumor uptake of 99mTc-HYNIC-(Ser)3-LTVPWY that is indicated the tumor specificity of the radiolabeled peptide on glioblastoma. Gamma planar imaging revealed that the U-87 MG tumor was clearly visualized at 1 h. Conclusion: The results of this study showed that the 99mTc-HYNIC-(Ser)3-LTVPWY peptide specifically accumulates in glioma and is, therefore, a promising probe for the diagnosis of glioma.