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Nanozeolite bioconjugates labeled with 223 Ra for targeted alpha therapy.

INTRODUCTION: Alpha particle emitting isotopes are of considerable interest for radionuclide therapy because of their high cytotoxicity and short path length. Among the many α emitters,223 Ra exhibits very attractive nuclear properties for application in radionuclide therapy. The decay of this radioisotope and its daughters is accompanied by the emission of four α-particles, releasing 27.9MeV of cumulative energy. Unfortunately the lack of an appropriate bifunctional ligand for radium has so far been a main obstacle for the application of223 Ra in receptor targeted therapy. In our studies we investigated the use of nanozeolite-Substance P bioconjugates as vehicles for223 Ra radionuclides for targeted α therapy.

METHODS: The sodium form of an A-type of nanozeolite (NaA) was synthesized using the template method. Next, the nanozeolite particles were conjugated to the Substance P (5-11) peptide fragment, which targets NK-1 receptors on glioma cells. The obtained bioconjugate was characterized by transmission emission spectroscopy, thermogravimetric analysis and dynamic light scattering analysis. The NaA-silane-PEG-SP(5-11) bioconjugates were labeled with223 Ra by exchange of the Na+ cation and the stability, receptor affinity and cytotoxicity of the obtained radiobioconjugates were tested.

RESULTS: The223 Ra-labeled nanozeolite bioconjugate almost quantitatively retains223 Ra in vitro after 6days, while the retention of decay products varies from 90 to 95%. The synthesized223 RaA-silane-PEG-SP(5-11) showed high receptor affinity toward NK-1 receptor expressing glioma cells and exhibited a high cytotoxic effect in vitro.

CONCLUSIONS: Substance P functionalized nanozeolite-A represents a viable solution for the use of the223 Ra in vivo generator as a therapeutic construct for targeting glioma cells.

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