Preparation and evaluation of ¹⁸⁸Re sulfide colloidal nanoparticles loaded biodegradable poly (L‐lactic acid) microspheres for radioembolization therapy

Abstract

Radioembolization with radioactive microspheres has been an effective method for the treatment of liver lesions. The aim of this study was to prepare carrier-free ¹⁸⁸ Re loaded poly (L-lactic acid) (PLLA) microspheres through ¹⁸⁸ Re sulfide colloidal nanoparticles (¹⁸⁸ Re-SC nanoparticles). The formation of ¹⁸⁸ Re-SC nanoparticles was confirmed by ultraviolet-visible spectrophotometry. The labeling yield of ¹⁸⁸ Re-SC nanoparticles was verified using the RTLC method. Effects of synthesis parameters on morphology and size of prepared ¹⁸⁸ Re-sulfide colloidal-PLLA microspheres (¹⁸⁸ Re-SC-PLLA microspheres) were studied by scanning electron microscopy. In vitro stability of ¹⁸⁸ Re-SC-PLLA microspheres was investigated in normal saline at room temperature and in human serum at 37°C. In vivo distribution studies and gamma camera imaging were performed in healthy BALB/c mice. The microspheres could be prepared with sizes between 13 and 48 μm (modal value 29 μm) and radiolabeling efficiency >99%. After incubation, the microspheres were found stable in vitro up to 72 hours. The biodistribution after intravenous injection in healthy BALB/c mice showed high accumulation in lung as a first capture pathway organ for microsphere followed by great retention over 48 hours for these microspheres. These data show that ¹⁸⁸ Re-SC-PLLA microspheres are suitable candidate for clinical studies.