Ra-224 Labeling of Calcium Carbonate Microparticles for Internal α-Therapy: Preparation, Stability and Biodistribution in Mice.

Internal therapy with -emitters should be well suited for micrometastatic disease. Radium-224 emits multiple -particles through its decay and has a convenient 3.6days of half-life. Despite its attractive properties, the use of Ra-224 has been limited to bone-seeking applications because it cannot be stably bound to a targeting molecule. Alternative delivery systems for Ra-224 are therefore of considerable interest. In this study, calcium carbonate microparticles are proposed as carriers for Ra-224, designed for local therapy of disseminated cancers in cavitary regions, such as peritoneal carcinomatosis. Calcium carbonate microparticles were radiolabeled by precipitation of Ra-224 on the particle surface, resulting in high labeling efficiencies for both Ra-224 and daughter Pb-212 and retention of more than 95% of these nuclides for up to 1week in vitro. The biodistribution after intraperitoneal administration of the Ra-224-labeled CaCO3 microparticles in immunodeficient mice revealed that the radioactivity mainly remained in the peritoneal cavity. In addition, the systemic distribution of Ra-224 was found to be strongly dependent on the amount of administered microparticles, with a reduced skeletal uptake of Ra-224 with increasing dose. The results altogether suggest that the Ra-224-labeled CaCO3 microparticles have promising properties for use as a localized internal -therapy of cavitary cancers.