Ra‐224 labeling of calcium carbonate microparticles for internal α‐therapy: Preparation, stability, and biodistribution in mice

Abstract

Internal therapy with α-emitters should be well suited for micrometastatic disease. Radium-224 emits multiple α-particles through its decay and has a convenient 3.6 days half-life. Despite its attractive properties, the use of ²²⁴Ra has been limited to bone-seeking applications because it cannot be stably bound to a targeting molecule. Alternative delivery systems for ²²⁴Ra are therefore of considerable interest. In this study, calcium carbonate (CaCO₃) microparticles are proposed as carriers for ²²⁴Ra, designed for local therapy of disseminated cancers in cavitary regions, such as peritoneal carcinomatosis. CaCO₃ microparticles were radiolabeled by precipitation of ²²⁴Ra on the particle surface, resulting in high labeling efficiencies for both ²²⁴Ra and daughter ²¹²Pb and retention of more than 95 % of these nuclides for up to one week in vitro. The biodistribution after intraperitoneal administration of the ²²⁴Ra-labeled CaCO₃ microparticles in immunodeficient mice revealed that the radioactivity mainly remained in the peritoneal cavity. In addition, the systemic distribution of ²²⁴Ra was found to be strongly dependent on the amount of administered microparticles, with a reduced skeletal uptake of ²²⁴Ra with increasing dose. The results altogether suggest that the ²²⁴Ra-labeled CaCO₃ microparticles have promising properties for use as a localized internal α-therapy of cavitary cancers.