{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T23:46:37Z","timestamp":1780616797398,"version":"3.54.1"},"reference-count":30,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,4,29]],"date-time":"2021-04-29T00:00:00Z","timestamp":1619654400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Norwegian Research Council","award":["282220"],"award-info":[{"award-number":["282220"]}]},{"name":"The Norwegian Research Council","award":["291228"],"award-info":[{"award-number":["291228"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Radium-224-labeled CaCO3 microparticles have been developed to treat peritoneal carcinomatosis. The microparticles function as carriers of 224Ra, facilitating intraperitoneal retention of the alpha-emitting radionuclide. It was necessary to control the size of microparticles in suspension over time and introduce a sterilization process for the clinical use of the radiopharmaceutical. Ethylenediamine tetra(methylene phosphonic acid) (EDTMP) was investigated as a stabilizing additive. The possibility of encapsulating the radiolabeled microparticles with an outer surface layer of CaCO3 for the improved retention of radioactivity by the carrier was studied. This work evaluated these steps of optimization and their effect on radiochemical purity, the biodistribution of radionuclides, and therapeutic efficacy. An EDTMP concentration of &gt;1% (w\/w) relative to CaCO3 stabilized the particle size for at least one week. Without EDTMP, the median particle size increased from ~5 \u00b5m to ~25 \u00b5m immediately after sterilization by autoclaving, and the larger microparticles sedimented rapidly in suspension. The percentage of adsorbed 224Ra progeny 212Pb increased from 56% to 94% at 2.4\u20132.5% (w\/w) EDTMP when the 224Ra-labeled microparticles were layer-encapsulated. The improved formulation also resulted in a suitable biodistribution of radionuclides in mice, as well as a survival benefit for mice with intraperitoneal ovarian or colorectal tumors.<\/jats:p>","DOI":"10.3390\/pharmaceutics13050634","type":"journal-article","created":{"date-parts":[[2021,4,29]],"date-time":"2021-04-29T10:30:41Z","timestamp":1619692241000},"page":"634","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Improved Formulation of 224Ra-Labeled Calcium Carbonate Microparticles by Surface Layer Encapsulation and Addition of EDTMP"],"prefix":"10.3390","volume":"13","author":[{"given":"Ruth Gong","family":"Li","sequence":"first","affiliation":[{"name":"Oncoinvent AS, 0484 Oslo, Norway"},{"name":"Institute of Clinical Medicine, University of Oslo, 0316 Oslo, Norway"},{"name":"Department of Radiation Biology, Institute of Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, 0379 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim","family":"Lindland","sequence":"additional","affiliation":[{"name":"Oncoinvent AS, 0484 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra Karen","family":"Tonstad","sequence":"additional","affiliation":[{"name":"Oncoinvent AS, 0484 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina Bj\u00f8rnlund","family":"B\u00f8nsdorff","sequence":"additional","affiliation":[{"name":"Oncoinvent AS, 0484 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9426-0062","authenticated-orcid":false,"given":"Asta","family":"Juzeniene","sequence":"additional","affiliation":[{"name":"Department of Radiation Biology, Institute of Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, 0379 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9556-3807","authenticated-orcid":false,"given":"Sara","family":"Westr\u00f8m","sequence":"additional","affiliation":[{"name":"Oncoinvent AS, 0484 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roy Hartvig","family":"Larsen","sequence":"additional","affiliation":[{"name":"Oncoinvent AS, 0484 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1002\/jlcr.3610","article-title":"Ra-224 labeling of calcium carbonate microparticles for internal \u03b1-therapy: Preparation, stability, and biodistribution in mice","volume":"61","author":"Malenge","year":"2018","journal-title":"J. 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