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

PLoS One. 2021 Mar 4;16(3):e0248133. doi: 10.1371/journal.pone.0248133. eCollection 2021.


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 (224Ra) is one such candidate that has been considered for use in combating micrometastatic disease. In our prior studies, a suspension of 224Ra-labeled calcium carbonate (CaCO3) microparticles was designed as a local therapy for disseminated cancers in the peritoneal cavity. The progenies of 224Ra, of which radon-220 (220Rn) 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 224Ra-CaCO3 microparticles can impact its therapeutic efficacy. In this study, we show that the diffusion of 220Rn was reduced in labeled CaCO3 suspensions as compared with cationic 224Ra solutions, both in air and liquid volumes. Furthermore, free-floating lead-212 (212Pb), which is generated from released 220Rn, had the potential to be re-adsorbed onto CaCO3 microparticles. Under conditions mimicking an in vivo environment, more than 70% of the 212Pb was adsorbed onto the CaCO3 at microparticle concentrations above 1 mg/mL. Further, the diffusion of 220Rn seemed to occur whether the microparticles were labeled by the surface adsorption of 224Ra or if the 224Ra was incorporated into the bulk of the microparticles. The therapeutic benefit of differently labeled 224Ra-CaCO3 microparticles after intraperitoneal administration was similar when examined in mice bearing intraperitoneal ovarian cancer xenografts. In conclusion, both the release of 220Rn and re-adsorption of 212Pb are features that have implications for the radiotherapeutic use of 224Ra-labeled CaCO3 microparticles. The release of 220Rn through diffusion may extend the effective range of alpha-particle dose deposition, and the re-adsorption of the longer lived 212Pb onto the CaCO3 microparticles may enhance the retention of this nuclide in the peritoneal cavity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Calcium Carbonate / chemistry*
  • Cell Proliferation
  • Female
  • Humans
  • Lead Radioisotopes / therapeutic use*
  • Mice
  • Mice, Nude
  • Ovarian Neoplasms / pathology
  • Ovarian Neoplasms / radiotherapy*
  • Radon / therapeutic use*
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays


  • Lead Radioisotopes
  • Lead-212
  • Radon-220
  • Calcium Carbonate
  • Radon

Grants and funding

This study was funded by: The Norwegian Research Council (www.forskningsradet.no, grant numbers 259820 and 282220, Recipients: EN and TBB/Oncoinvent AS respectively) and Oncoinvent AS www.oncoinvent.com). RHL is a board member of Oncoinvent AS, i.e. one of the funding entities. The funders provided support in the form of salaries for authors EN, ISJ, TBB and SW, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.