Design and optimization of imageable microspheres for locoregional cancer therapy.

Transarterial radioembolization (TARE) is an increasingly important technique for treating liver-based malignancies. Personalized treatment planning and dosimetry are not yet possible due to poor imageability of existing TARE agents. This study presents the design and development of a cohort of imageable glass microspheres that are compatible with readily available imaging equipment, including single-photon emission computed tomography (SPECT) and computed tomography (CT). A statistical modelling approach was used to investigate how the addition of holmium (Ho), a high atomic number and high k-edge element, to a Y(2)O(3)-Al(2)O(3)-SiO(2) (YAS) glass matrix impacts material properties such as density, CT imageability, and glass transition temperature (T(g)). The microspheres demonstrated excellent radiopacity, with Hounsfield Unit (HU) values ranging up to ~ 19,800 at 70 kVp, high thermal stability, exhibiting T(g) values up to 895 °C, no cytotoxic potential, and negligible ion leaching pre- and post-irradiation to 2600 GBq/g Ho-166, supporting their safety and efficacy for locoregional therapies. Statistical modelling elucidated how the fraction of holmium oxide content within the glass matrix impacts density, CT imageability, and T(g). The ability to visualize the microspheres intra- and post-operatively via CT and SPECT imaging, combined with stable radionuclide incorporation and high achievable specific activity, marks a significant advancement in TARE, and represents an opportunity to expand applicability to cancers beyond the liver.