Ra-224 labeling of calcium carbonate microparticles for internal α-therapy: Preparation, stability, and biodistribution in mice.

Sara Westrøm,Marion Malenge,Ida Sofie Jorstad,Øyvind S Bruland,Tina B Bønsdorff,Roy H Larsen,Elisa Napoli

doi:10.1002/jlcr.3610

Abstract

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

Highlights

Radiolabeling of CaCO3 microparticles was successful, and the results presented in Table 5 showed that both 224Ra and daughter nuclide 212Pb were adsorbed with yields above 80% by the microparticles, regardless of differences in median particle size and composition of the labeling solution
We have demonstrated that preparation of the 224Ra‐labeled CaCO3 microparticles by a simple and efficient procedure resulted in high labeling efficiencies
Calcium carbonate microparticles labeled with 224Ra on their surfaces were prepared efficiently and with high yields

Summary

| INTRODUCTION

The research efforts have culminated in 1 approved α‐emitting radiopharmaceutical, 223Ra‐dichloride (Xofigo®, Bayer), The use of internal α‐emitters to treat cancer has attracted which is used for treatment of patients with skeletal metassignificant attention during the last decade. The radioactivity (counts per minute, CPM) in the particle suspension (P) and washing solutions (W1 and W2) was measured, and the 212Pb labeling efficiency was estimated as the percentage of the total activity still bound to the microparticles after the labeling procedure:. It is assumed here that equilibrium between 224Ra and 212Pb in the samples is reached after 24 hours because the samples are expected to have a relatively even distribution of the 2 nuclides; ie, equilibrium will be reached faster than from a pure source of 224Ra. To determine the retention of 224Ra and 212Pb on the microparticles after labeling, the particles were incubated in 1‐ mL sucrose solution at room temperature. Samples of the injectates were used to estimate the actual injected dose per mouse before the injected dose was normalized to 10 kBq per mouse

| RESULTS

| DISCUSSION

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DISCLOSURES