Radon-220 diffusion from (224)Ra-labeled calcium carbonate microparticles: Some implications for radiotherapeutic use

Alpha-particle emitting radionuclides continue to be the subject of medical research because of their high energy and short range of action that facilitate effective cancer therapies. Radium-224 ((224)Ra) is one such candidate that has been considered for use in combating micrometastatic disease. In our prior studies, a suspension of (224)Ra-labeled calcium carbonate (CaCO(3)) microparticles was designed as a local therapy for disseminated cancers in the peritoneal cavity. The progenies of (224)Ra, of which radon-220 ((220)Rn) is the first, together contribute three of the four alpha particles in the decay chain. The proximity of the progenies to the delivery site at the time of decay of the (224)Ra-CaCO(3) microparticles can impact its therapeutic efficacy. In this study, we show that the diffusion of (220)Rn was reduced in labeled CaCO(3) suspensions as compared with cationic (224)Ra solutions, both in air and liquid volumes. Furthermore, free-floating lead-212 ((212)Pb), which is generated from released (220)Rn, had the potential to be re-adsorbed onto CaCO(3) microparticles. Under conditions mimicking an in vivo environment, more than 70% of the (212)Pb was adsorbed onto the CaCO(3) at microparticle concentrations above 1 mg/mL. Further, the diffusion of (220)Rn seemed to occur whether the microparticles were labeled by the surface adsorption of (224)Ra or if the (224)Ra was incorporated into the bulk of the microparticles. The therapeutic benefit of differently labeled (224)Ra-CaCO(3) microparticles after intraperitoneal administration was similar when examined in mice bearing intraperitoneal ovarian cancer xenografts. In conclusion, both the release of (220)Rn and re-adsorption of (212)Pb are features that have implications for the radiotherapeutic use of (224)Ra-labeled CaCO(3) microparticles. The release of (220)Rn through diffusion may extend the effective range of alpha-particle dose deposition, and the re-adsorption of the longer lived (212)Pb onto the CaCO(3) microparticles may enhance the retention of this nuclide in the peritoneal cavity.