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Calcium Carbonate Microparticles as Carriers of 224Ra: Impact of Specific Activity in Mice with Intraperitoneal Ovarian Cancer

[ Vol. 14 , Issue. 2 ]

Author(s):

Ruth Gong Li, Elisa Napoli, Ida Sofie Jorstad, Tina Bjørnlund Bønsdorff, Asta Juzeniene, Øyvind Sverre Bruland, Roy Hartvig Larsen and Sara Westrøm*   Pages 145 - 153 ( 9 )

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.

Affiliation:

Oncoinvent AS, Oslo, Oncoinvent AS, Oslo, Oncoinvent AS, Oslo, Oncoinvent AS, Oslo, Department of Radiation Biology, Institute of Cancer Research, the Norwegian Radium Hospital, Oslo University Hospital, Oslo, Institute of Clinical Medicine, University of Oslo, Oslo, Oncoinvent AS, Oslo, Oncoinvent AS, Oslo

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