Current Radiopharmaceuticals   Send Orders for Reprints to reprints@benthamscience.net Current Radiopharmaceuticals, 2021, 14, 145-153 145 RESEARCH ARTICLE Calcium Carbonate Microparticles as Carriers of 224 Ra: Impact of Specific Activity in Mice with Intraperitoneal Ovarian Cancer Ruth Gong Li 1,2,3 , Elisa Napoli 1,2,3 , Ida Sofie Jorstad 1 , Tina Bjørnlund Bønsdorff 1 , Asta Juzeniene 3 , Øyvind Sverre Bruland 2,4 , Roy Hartvig Larsen 1 and Sara Westrøm 1,* 1 Oncoinvent AS, Oslo, Norway; 2 Institute of Clinical Medicine, University of Oslo, Oslo, Norway; 3 Department of Radi- ation Biology, Institute of Cancer Research, the Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway; 4 Department of Oncology, the Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway ARTICLE HISTORY Received: May 29, 2020 Revised: September 28, 2020 Accepted: October 06, 2020 DOI: 10.2174/1874471013666201201102056 Abstract: Background: Patients with advanced-stage ovarian cancer face a poor prognosis be- cause of recurrent peritoneal cavity metastases following surgery and chemotherapy. Alpha-emit- ters 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 inher- ent skeletal accumulation must be overcome to facilitate intraperitoneal delivery of the radiation dose. Therefore, 224 Ra-labeled CaCO 3 microparticles have been developed. Objective: The antitumor effect of CaCO 3 microparticles as a carrier for 224 Ra was investigated, with an emphasis on the ratio of activity to mass dose of CaCO 3 , 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 224 Ra-labeled CaCO 3 microparticles with varying combinations of mass and activity dose, or cationic 224 Ra 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 224 Ra prolonged the survival compared with the control, equivalent median survival could be achieved with 224 Ra-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 CaCO 3 microparticles present a promising therapy against can- cer dissemination in body cavities. Keywords: Alpha therapy, calcium carbonate, microparticles, radium-224, 224Ra, peritoneal carcinomatosis, intraperitoneal, ovarian cancer. 1. INTRODUCTION Ovarian cancer presents numerous challenges, the most pressing of those being the survival rate; the worldwide five- year net survival is in the range of 30–50% [1]. Most cases are diagnosed at an advanced stage, with the disease dissemi- nated within the peritoneal cavity [2], which correlates to a poor prognosis [3]. The standard treatment for advanced-s- tage disease is cytoreductive surgery in combination with platinum-based chemotherapy [4]. Although this treatment regime initially gives some benefits, only a minority of wom- en with advanced ovarian cancer survive beyond five years after diagnosis [5], emphasizing the need for innovative ther- apies. *Address correspondence to this author at Oncoinvent AS, Oslo, Norway; Tel: +47 913 97 563; E-mail: westrom@oncoinvent.com Patients who have undergone surgical resection of all vis- ible tumors are at high risk of subsequent peritoneal relapse related to the presence of residual microscopic tumor de- posits and free-floating cancer cells [6]. Intraperitoneal (IP) treatment with various radionuclides has been evaluated clin- ically for the treatment of disseminated ovarian cancer [7-12]. Historically, radiocolloids based on β-emitters 198 Au and 32 P have been used with some success [13] but were eventually abandoned and replaced with chemotherapy be- cause of the more frequent incidence of late adverse effects [7, 14]. The use of colloids was subsequently exchanged with various monoclonal antibodies to which β-emitters were coupled, and several phase II clinical trials have been performed [8-11]. Unfortunately, the only phase III clinical trial investigating 90 Y coupled to an anti-MUC1 antibody failed to confirm both improved survival and reduced time to relapse [12]. 1874-4729/21 © 2021 Bentham Science Publishers This is an Open Access article published under CC BY 4.0 https://creativecommons.org/licenses/ by /4.0/legalcode