Development of radiopharmaceutical based on magnetic nanoparticles for targeted alpha-therapy

Abstract

The method of targeted radionuclide therapy using short-lived alpha emitters with a number of unique nuclear-physical and biochemical properties allows to achieve a high local cytotoxic effect with minimal impact on healthy tissues. The first alpha-radiopharmaceutical "Xofigo" represents radium dichloride-223, administered intravenously in the form of a solution, and has been used since 2013 in palliative therapy of bone metastases. The purpose of the present study was to investigate magnetic nanoparticles and their sorption ability towards radium-223 to develop nanoconstructs for targeted alpha-radiotherapy of oncological diseases. Magnetic nanoparticles based on magnetite were synthesized and characterized. The following two methods were used for synthesizing nanoparticles: the traditional method of co-precipitation and the new method based on a two-phase extraction system, when the formation of nanoparticles occurs on the interface layer. In the present study we select the system with polyethylene glycol (PEG) 3000. The method of direct radiolabeling of magnetite nanoparticles by sorption of radium-223, prepared using a 227Ac/227Th radioisotope generator, was developed. Optimal conditions were selected for ensuring the quantitative extraction of radium-223 from the solution by Fe3O4 nanoparticles. Magnetite nanoparticles coated with silica and PEG 3000 shells were developed for enhancing the aggregation stability and biocompatibility. It was found that the prepared nanoconstructs based on magnetite and radium-223 are sufficiently stable in physiological media and promising for application in targeted alpha-radiotherapy.