A Novel Single-Step-Labeled ²¹²Pb-CaCO₃ Microparticle for Internal Alpha Therapy: Preparation, Stability, and Preclinical Data from Mice

Lead-212 is recognized as a promising radionuclide for targeted alpha therapy for tumors. Many studies of ²¹²Pb-labeling of various biomolecules through bifunctional chelators have been conducted. Another approach to exploiting the cytotoxic effect is coupling the radionuclide to a microparticle acting as a carrier vehicle, which could be used for treating disseminated cancers in body cavities. Calcium carbonate may represent a suitable material, as it is biocompatible, biodegradable, and easy to synthesize. In this work, we explored ²¹²Pb-labeling of various CaCO₃ microparticles and developed a protocol that can be straightforwardly implemented by clinicians. Vaterite microparticles stabilized by pamidronate were effective as ²¹²Pb carriers; labeling yields of ≥98% were achieved, and ²¹²Pb was strongly retained by the particles in an in vitro stability assessment. Moreover, the amounts of ²¹²Pb reaching the kidneys, liver, spleen, and skeleton of mice following intraperitoneal (i.p.) administration were very low compared to i.p. injection of unbound ²¹²Pb²⁺, indicating that CaCO₃-bound ²¹²Pb exhibited stability when administered intraperitoneally. Therapeutic efficacy was observed in a model of i.p. ovarian cancer for all the tested doses, ranging from 63 to 430 kBq per mouse. Lead-212-labeled CaCO₃ microparticles represent a promising candidate for treating intracavitary cancers.