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Article

Improved Formulation of 224Ra-Labeled Calcium Carbonate Microparticles by Surface Layer Encapsulation and Addition of EDTMP

1
Oncoinvent AS, 0484 Oslo, Norway
2
Institute of Clinical Medicine, University of Oslo, 0316 Oslo, Norway
3
Department of Radiation Biology, Institute of Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, 0379 Oslo, Norway
*
Author to whom correspondence should be addressed.
Academic Editor: Leonard I. Wiebe
Pharmaceutics 2021, 13(5), 634; https://doi.org/10.3390/pharmaceutics13050634
Received: 6 April 2021 / Revised: 22 April 2021 / Accepted: 27 April 2021 / Published: 29 April 2021
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 >1% (w/w) relative to CaCO3 stabilized the particle size for at least one week. Without EDTMP, the median particle size increased from ~5 µm to ~25 µm 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 2.4–2.5% (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. View Full-Text
Keywords: radiopharmaceutical; radionuclide therapy; alpha therapy; alpha emitter; calcium carbonate; microparticles; radium; peritoneal carcinomatosis radiopharmaceutical; radionuclide therapy; alpha therapy; alpha emitter; calcium carbonate; microparticles; radium; peritoneal carcinomatosis
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MDPI and ACS Style

Li, R.G.; Lindland, K.; Tonstad, S.K.; Bønsdorff, T.B.; Juzeniene, A.; Westrøm, S.; Larsen, R.H. Improved Formulation of 224Ra-Labeled Calcium Carbonate Microparticles by Surface Layer Encapsulation and Addition of EDTMP. Pharmaceutics 2021, 13, 634. https://doi.org/10.3390/pharmaceutics13050634

AMA Style

Li RG, Lindland K, Tonstad SK, Bønsdorff TB, Juzeniene A, Westrøm S, Larsen RH. Improved Formulation of 224Ra-Labeled Calcium Carbonate Microparticles by Surface Layer Encapsulation and Addition of EDTMP. Pharmaceutics. 2021; 13(5):634. https://doi.org/10.3390/pharmaceutics13050634

Chicago/Turabian Style

Li, Ruth G., Kim Lindland, Sandra K. Tonstad, Tina B. Bønsdorff, Asta Juzeniene, Sara Westrøm, and Roy H. Larsen. 2021. "Improved Formulation of 224Ra-Labeled Calcium Carbonate Microparticles by Surface Layer Encapsulation and Addition of EDTMP" Pharmaceutics 13, no. 5: 634. https://doi.org/10.3390/pharmaceutics13050634

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