Effective therapy with Bismuth-212 labeled macroaggregated albumin in orthotopic mouse breast tumor models
Intravascularly administered radiation therapy using beta (β-)-emitting radioisotopes has relied on either intravenously injected radiolabeled peptides that target cancer or radiolabeled microspheres that are trapped in the tumor following intra-arterial delivery. More recently, targeted intravenous...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-05-01
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| Series: | Frontiers in Chemistry |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fchem.2023.1204872/full |
| _version_ | 1797829936489168896 |
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| author | Nathan Kauffman Satyendra Kumar Singh James Morrison Kurt R. Zinn |
| author_facet | Nathan Kauffman Satyendra Kumar Singh James Morrison Kurt R. Zinn |
| author_sort | Nathan Kauffman |
| collection | DOAJ |
| description | Intravascularly administered radiation therapy using beta (β-)-emitting radioisotopes has relied on either intravenously injected radiolabeled peptides that target cancer or radiolabeled microspheres that are trapped in the tumor following intra-arterial delivery. More recently, targeted intravenous radiopeptide therapies have explored the use of alpha (α)-particle emitting radioisotopes, but microspheres radiolabeled with α-particle emitters have not yet been studied. Here, FDA-approved macroaggregated albumin (MAA) particles were radiolabeled with Bismuth-212 (Bi-212-MAA) and evaluated using clonogenic and survival assays in vitro and using immune-competent mouse models of breast cancer. The in vivo biodistribution of Bi-212-MAA was investigated in Balb/c and C57BL/6 mice with 4T1 and EO771 orthotopic breast tumors, respectively. The same orthotopic breast cancer models were used to evaluate the treatment efficacy of Bi-212-MAA. Our results showed that macroaggregated albumin can be stably radiolabeled with Bi-212 and that Bi-212-MAA can deliver significant radiation therapy to reduce the growth and clonogenic potential of 4T1 and EO771 cells in vitro. Additionally, Bi-212-MAA treatment upregulated γH2AX and cleaved Caspase-3 expression in 4T1 cells. Biodistribution analyses showed 87–93% of the Bi-212-MAA remained in 4T1 and EO771 tumors 2 and 4 h after injection. Following single-tumor treatments with Bi-212-MAA there was a significant reduction in the growth of both 4T1 and EO771 breast tumors over the 18-day monitoring period. Overall, these findings showed that Bi-212-MAA was stably radiolabeled and inhibited breast cancer growth. Bi-212-MAA is an exciting platform to study α-particle therapy and will be easily translatable to larger animal models and human clinical trials. |
| first_indexed | 2024-04-09T13:28:07Z |
| format | Article |
| id | doaj.art-07066aaacbc340d9b7b433ff0297e14f |
| institution | Directory Open Access Journal |
| issn | 2296-2646 |
| language | English |
| last_indexed | 2024-04-09T13:28:07Z |
| publishDate | 2023-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Chemistry |
| spelling | doaj.art-07066aaacbc340d9b7b433ff0297e14f2023-05-10T05:20:13ZengFrontiers Media S.A.Frontiers in Chemistry2296-26462023-05-011110.3389/fchem.2023.12048721204872Effective therapy with Bismuth-212 labeled macroaggregated albumin in orthotopic mouse breast tumor modelsNathan Kauffman0Satyendra Kumar Singh1James Morrison2Kurt R. Zinn3Comparative Medicine and Integrative Biology, Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI, United StatesDepartment of Biomedical Engineering, Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI, United StatesAdvanced Radiology Services, Grand Rapids, MI, United StatesDepartments of Radiology, Biomedical Engineering, Small Animal Clinical Sciences, Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI, United StatesIntravascularly administered radiation therapy using beta (β-)-emitting radioisotopes has relied on either intravenously injected radiolabeled peptides that target cancer or radiolabeled microspheres that are trapped in the tumor following intra-arterial delivery. More recently, targeted intravenous radiopeptide therapies have explored the use of alpha (α)-particle emitting radioisotopes, but microspheres radiolabeled with α-particle emitters have not yet been studied. Here, FDA-approved macroaggregated albumin (MAA) particles were radiolabeled with Bismuth-212 (Bi-212-MAA) and evaluated using clonogenic and survival assays in vitro and using immune-competent mouse models of breast cancer. The in vivo biodistribution of Bi-212-MAA was investigated in Balb/c and C57BL/6 mice with 4T1 and EO771 orthotopic breast tumors, respectively. The same orthotopic breast cancer models were used to evaluate the treatment efficacy of Bi-212-MAA. Our results showed that macroaggregated albumin can be stably radiolabeled with Bi-212 and that Bi-212-MAA can deliver significant radiation therapy to reduce the growth and clonogenic potential of 4T1 and EO771 cells in vitro. Additionally, Bi-212-MAA treatment upregulated γH2AX and cleaved Caspase-3 expression in 4T1 cells. Biodistribution analyses showed 87–93% of the Bi-212-MAA remained in 4T1 and EO771 tumors 2 and 4 h after injection. Following single-tumor treatments with Bi-212-MAA there was a significant reduction in the growth of both 4T1 and EO771 breast tumors over the 18-day monitoring period. Overall, these findings showed that Bi-212-MAA was stably radiolabeled and inhibited breast cancer growth. Bi-212-MAA is an exciting platform to study α-particle therapy and will be easily translatable to larger animal models and human clinical trials.https://www.frontiersin.org/articles/10.3389/fchem.2023.1204872/fullcancer therapymacroaggregated albumin (MAA)interventional radiology (IR)Bismuth-212 (Bi-212)alpha-particleradiopharmaceutical |
| spellingShingle | Nathan Kauffman Satyendra Kumar Singh James Morrison Kurt R. Zinn Effective therapy with Bismuth-212 labeled macroaggregated albumin in orthotopic mouse breast tumor models Frontiers in Chemistry cancer therapy macroaggregated albumin (MAA) interventional radiology (IR) Bismuth-212 (Bi-212) alpha-particle radiopharmaceutical |
| title | Effective therapy with Bismuth-212 labeled macroaggregated albumin in orthotopic mouse breast tumor models |
| title_full | Effective therapy with Bismuth-212 labeled macroaggregated albumin in orthotopic mouse breast tumor models |
| title_fullStr | Effective therapy with Bismuth-212 labeled macroaggregated albumin in orthotopic mouse breast tumor models |
| title_full_unstemmed | Effective therapy with Bismuth-212 labeled macroaggregated albumin in orthotopic mouse breast tumor models |
| title_short | Effective therapy with Bismuth-212 labeled macroaggregated albumin in orthotopic mouse breast tumor models |
| title_sort | effective therapy with bismuth 212 labeled macroaggregated albumin in orthotopic mouse breast tumor models |
| topic | cancer therapy macroaggregated albumin (MAA) interventional radiology (IR) Bismuth-212 (Bi-212) alpha-particle radiopharmaceutical |
| url | https://www.frontiersin.org/articles/10.3389/fchem.2023.1204872/full |
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