A Novel Single-Step-Labeled <sup>212</sup>Pb-CaCO<sub>3</sub> Microparticle for Internal Alpha Therapy: Preparation, Stability, and Preclinical Data from Mice
Lead-212 is recognized as a promising radionuclide for targeted alpha therapy for tumors. Many studies of <sup>212</sup>Pb-labeling of various biomolecules through bifunctional chelators have been conducted. Another approach to exploiting the cytotoxic effect is coupling the radionuclide...
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MDPI AG
2021-11-01
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| Online Access: | https://www.mdpi.com/1996-1944/14/23/7130 |
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| author | Ruth Gong Li Kim Lindland Tina Bjørnlund Bønsdorff Sara Westrøm Roy Hartvig Larsen |
| author_facet | Ruth Gong Li Kim Lindland Tina Bjørnlund Bønsdorff Sara Westrøm Roy Hartvig Larsen |
| author_sort | Ruth Gong Li |
| collection | DOAJ |
| description | Lead-212 is recognized as a promising radionuclide for targeted alpha therapy for tumors. Many studies of <sup>212</sup>Pb-labeling of various biomolecules through bifunctional chelators have been conducted. Another approach to exploiting the cytotoxic effect is coupling the radionuclide to a microparticle acting as a carrier vehicle, which could be used for treating disseminated cancers in body cavities. Calcium carbonate may represent a suitable material, as it is biocompatible, biodegradable, and easy to synthesize. In this work, we explored <sup>212</sup>Pb-labeling of various CaCO<sub>3</sub> microparticles and developed a protocol that can be straightforwardly implemented by clinicians. Vaterite microparticles stabilized by pamidronate were effective as <sup>212</sup>Pb carriers; labeling yields of ≥98% were achieved, and <sup>212</sup>Pb was strongly retained by the particles in an in vitro stability assessment. Moreover, the amounts of <sup>212</sup>Pb reaching the kidneys, liver, spleen, and skeleton of mice following intraperitoneal (i.p.) administration were very low compared to i.p. injection of unbound <sup>212</sup>Pb<sup>2+</sup>, indicating that CaCO<sub>3</sub>-bound <sup>212</sup>Pb exhibited stability when administered intraperitoneally. Therapeutic efficacy was observed in a model of i.p. ovarian cancer for all the tested doses, ranging from 63 to 430 kBq per mouse. Lead-212-labeled CaCO<sub>3</sub> microparticles represent a promising candidate for treating intracavitary cancers. |
| first_indexed | 2024-03-10T04:50:02Z |
| format | Article |
| id | doaj.art-1d827a64dec242d296622132b13538f8 |
| institution | Directory Open Access Journal |
| issn | 1996-1944 |
| language | English |
| last_indexed | 2024-03-10T04:50:02Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Materials |
| spelling | doaj.art-1d827a64dec242d296622132b13538f82023-11-23T02:38:43ZengMDPI AGMaterials1996-19442021-11-011423713010.3390/ma14237130A Novel Single-Step-Labeled <sup>212</sup>Pb-CaCO<sub>3</sub> Microparticle for Internal Alpha Therapy: Preparation, Stability, and Preclinical Data from MiceRuth Gong Li0Kim Lindland1Tina Bjørnlund Bønsdorff2Sara Westrøm3Roy Hartvig Larsen4Oncoinvent AS, 0484 Oslo, NorwayOncoinvent AS, 0484 Oslo, NorwayOncoinvent AS, 0484 Oslo, NorwayOncoinvent AS, 0484 Oslo, NorwayOncoinvent AS, 0484 Oslo, NorwayLead-212 is recognized as a promising radionuclide for targeted alpha therapy for tumors. Many studies of <sup>212</sup>Pb-labeling of various biomolecules through bifunctional chelators have been conducted. Another approach to exploiting the cytotoxic effect is coupling the radionuclide to a microparticle acting as a carrier vehicle, which could be used for treating disseminated cancers in body cavities. Calcium carbonate may represent a suitable material, as it is biocompatible, biodegradable, and easy to synthesize. In this work, we explored <sup>212</sup>Pb-labeling of various CaCO<sub>3</sub> microparticles and developed a protocol that can be straightforwardly implemented by clinicians. Vaterite microparticles stabilized by pamidronate were effective as <sup>212</sup>Pb carriers; labeling yields of ≥98% were achieved, and <sup>212</sup>Pb was strongly retained by the particles in an in vitro stability assessment. Moreover, the amounts of <sup>212</sup>Pb reaching the kidneys, liver, spleen, and skeleton of mice following intraperitoneal (i.p.) administration were very low compared to i.p. injection of unbound <sup>212</sup>Pb<sup>2+</sup>, indicating that CaCO<sub>3</sub>-bound <sup>212</sup>Pb exhibited stability when administered intraperitoneally. Therapeutic efficacy was observed in a model of i.p. ovarian cancer for all the tested doses, ranging from 63 to 430 kBq per mouse. Lead-212-labeled CaCO<sub>3</sub> microparticles represent a promising candidate for treating intracavitary cancers.https://www.mdpi.com/1996-1944/14/23/7130lead-212alpha therapyradionuclide therapyradiopharmaceuticalcalcium carbonatemicroparticles |
| spellingShingle | Ruth Gong Li Kim Lindland Tina Bjørnlund Bønsdorff Sara Westrøm Roy Hartvig Larsen A Novel Single-Step-Labeled <sup>212</sup>Pb-CaCO<sub>3</sub> Microparticle for Internal Alpha Therapy: Preparation, Stability, and Preclinical Data from Mice Materials lead-212 alpha therapy radionuclide therapy radiopharmaceutical calcium carbonate microparticles |
| title | A Novel Single-Step-Labeled <sup>212</sup>Pb-CaCO<sub>3</sub> Microparticle for Internal Alpha Therapy: Preparation, Stability, and Preclinical Data from Mice |
| title_full | A Novel Single-Step-Labeled <sup>212</sup>Pb-CaCO<sub>3</sub> Microparticle for Internal Alpha Therapy: Preparation, Stability, and Preclinical Data from Mice |
| title_fullStr | A Novel Single-Step-Labeled <sup>212</sup>Pb-CaCO<sub>3</sub> Microparticle for Internal Alpha Therapy: Preparation, Stability, and Preclinical Data from Mice |
| title_full_unstemmed | A Novel Single-Step-Labeled <sup>212</sup>Pb-CaCO<sub>3</sub> Microparticle for Internal Alpha Therapy: Preparation, Stability, and Preclinical Data from Mice |
| title_short | A Novel Single-Step-Labeled <sup>212</sup>Pb-CaCO<sub>3</sub> Microparticle for Internal Alpha Therapy: Preparation, Stability, and Preclinical Data from Mice |
| title_sort | novel single step labeled sup 212 sup pb caco sub 3 sub microparticle for internal alpha therapy preparation stability and preclinical data from mice |
| topic | lead-212 alpha therapy radionuclide therapy radiopharmaceutical calcium carbonate microparticles |
| url | https://www.mdpi.com/1996-1944/14/23/7130 |
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