Abstract

Background: Patients with advanced-stage ovarian cancer face a poor prognosis because of recurrent peritoneal cavity metastases following surgery and chemotherapy. Alpha-emitters may enable the efficient treatment of such disseminated diseases because of their short range and highly energetic radiation. Radium-224 is a candidate α-emitter due to its convenient 3.6-day half-life, with more than 90% of the decay energy originating from α-particles. However, its inherent skeletal accumulation must be overcome to facilitate intraperitoneal delivery of the radiation dose. Therefore, ²²⁴Ra-labeled CaCO₃ microparticles have been developed.

Objective: The antitumor effect of CaCO₃ microparticles as a carrier for ²²⁴Ra was investigated, with an emphasis on the ratio of activity to mass dose of CaCO₃, that is, specific activity.

Methods: Nude athymic mice were inoculated intraperitoneally with human ovarian cancer cells (ES-2) and treated with a single intraperitoneal injection of ²²⁴Ra-labeled CaCO₃ microparticles with varying combinations of mass and activity dose, or cationic ²²⁴Ra in solution. Survival and ascites volume at sacrifice were evaluated.

Results: Significant therapeutic effect was achieved for all tested specific activities ranging from 0.4 to 4.6 kBq/mg. Although treatment with a mean activity dose of 1305 kBq/kg of cationic ²²⁴Ra prolonged the survival compared with the control, equivalent median survival could be achieved with ²²⁴Ra-labeled microparticles with a mean dose of only 420 kBq/kg. The best outcome was achieved with the highest specific activities (2.6 and 4.6 kBq/mg).

Conclusion: Radium-224-labeled CaCO₃ microparticles present a promising therapy against cancer dissemination in body cavities.

Keywords: Alpha therapy, calcium carbonate, microparticles, radium-224, 224Ra, peritoneal carcinomatosis, intraperitoneal, ovarian cancer.