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|Title:||TiO2 nanoparticles as carries of 225Ac/213Bi in vivo generator|
|Authors:||LESZCZUK Edyta; PIOTROWSKA A; BILEWICZ Aleksander; MORGENSTERN Alfred; BRUCHERTSEIFER Frank|
|Citation:||Proceedings of the 8th Symposium on Targeted Alpha Therapy p. 30|
|Publisher:||Oak Ridge National Laboratory|
|Type:||Articles in periodicals and books|
|Abstract:||Alpha particle emitting isotopes are in considerable interest for radionuclide therapy because of their high cytotoxicity and short path length. Unfortunately, all available emitters have serious disadvantages: 211At forms weak bond with carbon atoms in the biomolecule and in the case of 212Bi and 213Bi short half-life often limits the application of these nuclides. However, the short half-life of 212Bi and 213Bi could be effectively lengthened by binding the parent radionuclide 212Pb (t1/2 = 10.6 h) or 225Ac (t1/2 = 10 d) to the biomolecule, thereby effectively extending the use of short half-life 212Bi and 213Bi. In addition, in vivo generator delivers much greater dose per unit of administered activity compared to 212Bi and 213Bi alone. In our studies we investigated the use of TiO2 nanoparticles as potential carriers for 225Ac/213Bi in vivo generator. The TiO2 nanoparticles have unique properties like: high specific surface, high affinity for multivalent cations and simple way of synthesis, which are useful in the process of labelling. Commercially available (e.g. P-25 Degussa) and synthesised in our laboratory nanoparticles were used in experiments. The nanoparticles were characterized by TEM, SEM, DLS and NanoSight techniques. In our experiments we tested two different methods of labelling. The first one was based on the possibility of formation strong bonds with certain cations on the surface of the nanopraticles. In the second one, TiO2 nanoparticles were doped with 225Ac during the process of synthesis. In both cases we obtained high yields of labelling (>99%). Afterwards, the stability of labelled nanoparticles was examined in 0.9% NaCl, 10-3M EDTA, solutions of biologically active substances (cysteine, glutathione) and human serum. In the case of TiO2 nanoparticles with 225Ac, which was built in the crystalline structure, the leakage of 225Ac and its daughter radionuclides was not significant in any of solutions, even when the incubation time was extended to 10 days. The leakage in serum, from nanoparticles with adsorbed 225Ac on their surface, was slightly higher, but still insignificant. The obtained results show high stability of labelled nanoparticles and allow to begin further experiments, which are based on modification of the surface by silane compounds which enable binding TiO2 nanoparticles to the biomolecules.|
|JRC Directorate:||Nuclear Safety and Security|
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