Radioactive holmium phosphate microspheres for cancer treatment

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Abstract

The aim of this study was the development of radioactive holmium phosphate microspheres (HoPO4-MS) with a high holmium content and that are stable in human serum for selective internal radiation therapy (SIRT) of liver cancer. To this end, holmium acetylacetonate microspheres (HoAcAc-MS) were prepared (34.2±1.0μm in diameter, holmium content of 46.2±0.8 and density of 1.7g/cm3) via an emulsification and solvent evaporation method. The concentration of HoAcAc in the organic solvent, the temperature of emulsification and the stirring speed were varied for the preparation of the HoAcAc-MS to obtain microspheres with different diameters ranging from 11 to 35μm. Subsequently, the AcAc ligands of the HoAcAc-MS were replaced by phosphate ions by simply incubating neutron irradiated HoAcAc-MS in a phosphate buffer solution (0.116M, pH 4.2) to yield radioactive HoPO4-MS. The obtained microspheres were analyzed using different techniques such as SEM-EDS, ICP-OES and HPLC. The prepared HoPO4-MS (29.5±1.2μm in diameter and a density of 3.1g/cm3) present an even higher holmium content (52wt%) than the HoAcAc-MS precursor (46wt%). Finally, the stability of the HoPO4-MS was tested by incubation in human serum at 37°C which showed no visible changes of the microspheres morphology and only 0.1% of holmium release was observed during the 2weeks period of incubation. In conclusion, this study shows that stable radioactive HoPO4-MS can be prepared with suitable properties to be used for cancer therapy.

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