A Novel Single-Step-Labeled (212)Pb-CaCO(3) 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 (212)Pb-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 (212)Pb-labeling of various CaCO(3) microparticles and developed a protocol that can be straightforwardly implemented by clinicians. Vaterite microparticles stabilized by pamidronate were effective as (212)Pb carriers; labeling yields of ≥98% were achieved, and (212)Pb was strongly retained by the particles in an in vitro stability assessment. Moreover, the amounts of (212)Pb reaching the kidneys, liver, spleen, and skeleton of mice following intraperitoneal (i.p.) administration were very low compared to i.p. injection of unbound (212)Pb(2+), indicating that CaCO(3)-bound (212)Pb 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 CaCO(3) microparticles represent a promising candidate for treating intracavitary cancers.