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|Title:||223Ra-NaA-silane-PEG-SP(5-11) radiobioconjugate as a new potential radiopharmaceutical for targeted α therapy of glioblastoma multiforme|
|Authors:||MAJKOWSKA PILIP Agnieszka; KOZMINSKI P; PIOTROWSKA A; BRUCHERTSEIFER Frank; MORGENSTERN Alfred; BONELLI Milton; LAURENZA Marta; BILEWICZ Aleksander|
|Citation:||EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING vol. 42 no. S1 p. S244-S245|
|Type:||Articles in periodicals and books|
|Abstract:||Aim: Despite all current forms of treatment such as advanced surgery techniques, radiation therapy and chemotherapy, the life expectancy of patients diagnosed with glioblastoma multiforme (GBM) is 12 to 15 months displaying the worst median overall survival among all human neoplasms. According to the cancer stem cell hypothesis, malignant gliomas arise from mutated, developmentally arrested multipotent progenitor cells (“glioma stem cells”) that sustain tumor growth and are intrinsically resistant to radio- and chemotherapy. Targeted alpha therapy has been shown to overcome chemo- and radioresistance in vitro and thus presents a promising approach for therapy of GBM. The aim of this study is to investigate the use of radiobioconjugate - 223Ra-NaA-silane- PEG-SP(5-11) for targeted α therapy of gliomas. Materials and methods: Sodium form of an A type of nanozeolite (NaA) wassynthesized using the hydrothermal method. Size distribution and shape of NaA nanozeolite particles were characterized by dynamic light scattering analysis (DLS), scaning elektron microscopy (SEM) and transmission emission spectroscopy (TEM). PEG linker (2000 kDa) comprising the silane group at one end and Nsuccinimid ester (NHS) at the second was used for synthesis of silane-PEG-SP(5-11) bioconjugate. The obtained bioconjugate was characterized by thermogravimetric (TGA) andDLS analysis. Next the NaA-silane-PEG-SP(5-11) bioconjugates were labelled with 223Ra by exchange of Na+ cation and stability of obtained radiobioconjugates were tested in various biological fluids. Cell viability was assayed using the MTS colorimetric assay. Results: Nanosized zeolites were successfully prepared through hydrothermal synthesis. The TGA results has shown that silane-PEG-SP(5-11) molecules are covalently attach to the NaA nanozeolite surface. 223Raα-particle emitting radionuclide, has been absorbed in the nanometer-sized NaA zeolite (30-70 nm) trough simple ion exchange. The 223Ra labeled nanozeolite bioconjugate successfully retain 95% fraction of the daughter products without compromising the tumoricidal properties of the radiation. It is worth to notice, that the release of the decay product from 223Ra is a negligible problem, because 75% of the α-particles energy are emitted within a 4 seconds after the 223Ra decay. Cytotoxicity assays showed a reduction of viability of GBM cells as well as GBM stem cells after incubation with 223Ra-NaAsilane- PEG-SP(5-11) in a dose dependent manner. Cell viability also decreased with increasing incubation times. Conclusion: Targeted alpha therapy with 223Ra-NaA-silane-PEG-SP(5-11) is a promising approach for treatment of GBM which is resistant for conventional therapies and warrants further investigation in vivo.|
|JRC Directorate:||Nuclear Safety and Security|
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