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

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 of half‐life. Despite its attractive properties, the use of (224)Ra has been limited to bone‐seeking applications because it cannot be stably bound to a targeting molecule. Alternative delivery systems for (224)Ra are therefore of considerable interest. In this study, calcium carbonate microparticles are proposed as carriers for (224)Ra, designed for local therapy of disseminated cancers in cavitary regions, such as peritoneal carcinomatosis. Calcium carbonate microparticles were radiolabeled by precipitation of (224)Ra on the particle surface, resulting in high labeling efficiencies for both (224)Ra and daughter (212)Pb and retention of more than 95% of these nuclides for up to 1 week in vitro. The biodistribution after intraperitoneal administration of the (224)Ra‐labeled CaCO(3) microparticles in immunodeficient mice revealed that the radioactivity mainly remained in the peritoneal cavity. In addition, the systemic distribution of (224)Ra was found to be strongly dependent on the amount of administered microparticles, with a reduced skeletal uptake of (224)Ra with increasing dose. The results altogether suggest that the (224)Ra‐labeled CaCO(3) microparticles have promising properties for use as a localized internal α‐therapy of cavitary cancers.