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

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.

Therapeutic Effect of α-Emitting 224Ra-Labeled Calcium Carbonate Microparticles in Mice with Intraperitoneal Ovarian Cancer

“…Residue from the CaCO 3 microparticles was observed at necropsy up to day 7 in the previously reported biodistribution studies [24] but was not seen in the therapy studies performed here when the mice were sacrificed between 26 and 70 days after administration. Even though particle residue was seen at the early time points, they did not cause adhesions, and the lack of a permanent implant or other signs of remaining residue after day 26 suggests that the CaCO 3 microparticles are well tolerated and supports the general notion of CaCO 3 being a biocompatible and biodegradable material.…”

“…The preparation of 224 Ra-labeled CaCO 3 microparticles has been described in detail elsewhere [24] . In brief, CaCO 3 microparticles were prepared by a spontaneous precipitation method which yielded particles with individual diameters ranging from 3 to 15 μm.…”

“…A method for labeling of calcium carbonate (CaCO 3 ) microparticles with the α-emitter 224 Ra was recently reported [24] . Radium-224 has attractive properties for α-therapy as it produces four α-particles per decay and has a convenient half-life of 3.6 days.…”

“…Radium-224 has attractive properties for α-therapy as it produces four α-particles per decay and has a convenient half-life of 3.6 days. After IP administration of the 224 Ra-labeled microparticles in athymic nude mice, the radioactivity mainly remained intra-abdominally with a promising distribution [24] . In the current study, the therapeutic potential of IP-administered 224 Ra-labeled microparticles was explored in murine models of IP growing tumors, and a preliminary evaluation of the tolerability of the treatment was performed.…”

Design and Evaluation of 223Ra-Labeled and Anti-PSMA Targeted NaA Nanozeolites for Prostate Cancer Therapy–Part I

“…Previous attempts to bind 223 Ra within liposomes have not been successful because of their low stability in physiological fluids and relatively large diameter [ 28 , 29 ]. However, the next studies have shown better immobilization of 223 Ra in magnetite nanoparticles [ 30 ], hydroxyapatites [ 31 ], barium sulfate nanoparticles [ 32 ], and CaCO 3 microparticles [ 33 ]. In addition, the procedure of incorporation of 223 Ra in NaA nanozeolites was developed by our group [ 34 , 35 ].…”