Optimization of holmium-166 microspheres suspension for intratumoral microbrachytherapy

Abstract

Holmium-166 microbrachytherapy is a minimally invasive treatment for solid tumors, where radioactive holmium-166 microspheres (166Ho-MS) are injected directly into the tumor. High-energy beta radiation damages the tumor without compromising surrounding tissues. Previous studies showed up to 83 % tumor reduction despite suboptimal dose delivery, largely due to rapid sedimentation of 166Ho-MS in the aqueous Pluronic-based suspension. This study aimed to evaluate and improve the suspension by testing other carrier fluids with higher viscosity and/or density. Several fluids were selected or composed and evaluated for static sedimentation of different nonradioactive 165Ho-MS types in 1 mL suspensions, fluid expulsion under standardized pressure through 20 and 22G needles (40 and 75 mm), and the impact of external cobalt-60 radiation (0.3–32.5 kGy) on fluid properties (density, osmolality, pH, and viscosity). Most new fluids (14/16) had lower sedimentation rates than the current Pluronic-based fluid. Poly-L-lactic acid, phosphate, and hydroxide microspheres showed >1 h total sedimentation time in 7, 3, and 2 fluids, respectively, which would allow resuspension and homogeneous injection during microbrachytherapy. Sodium hyaluronate (Sh) and colloidal microcrystalline cellulose (Mcc) exhibited minimal to no sedimentation. Most fluids (14/17) had expulsions below set criterium of 15 s/mL for 20 and 22G x 40 mm needles. Radiation caused marked changes in pH and viscosity for most fluids, including Sh with viscosity decreases after relatively low doses. Mcc was the sole promising candidate for 166Ho-MS suspension to advance microbrachytherapy, with no sedimentation, proper expulsion, and good retention of pH and viscosity after irradiation (∼75 %).