Nanozeolite bioconjugates labeled with 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, 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 of Ra in receptor targeted therapy. In our studies we investigated the use of nanozeolite-Substance P bioconjugates as vehicles for 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 with Ra by exchange of the Na cation and the stability, receptor affinity and cytotoxicity of the obtained radiobioconjugates were tested.

RESULTS

The Ra-labeled nanozeolite bioconjugate almost quantitatively retains Ra in vitro after 6days, while the retention of decay products varies from 90 to 95%. The synthesized 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 the Ra in vivo generator as a therapeutic construct for targeting glioma cells.