Cobaltabis(Dicarbollide) [o-COSAN]− for Boron Neutron Capture Therapy of Head and Neck Cancer: Biodistribution and Irradiation Studies in an Experimental Oral Cancer Model

Background: Boron neutron capture therapy (BNCT) is a tumor-selective particle radiotherapy that combines preferential boron accumulation in tumors and neutron irradiation. Based on previous studies in tumor-bearing mice, this study evaluated the biodistribution of the sodium salt of cobaltabis(dica...

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Authors: Palmieri, Mónica A., Monti Hughes, Andrea, Trivillin, Verónica A., Garabalino, Marcela A., Ramos, Paula S., Thorp, Silvia I., Curotto, Paula, Pozzi, Emiliano C. C., Nuez Martínez, Miquel, Teixidor, Francesc, Viñas, Clara, Schwint, Amanda E.
Format: article
Status:Published version
Publication Date:2024
Country:España
Institution:Consejo Superior de Investigaciones Científicas (CSIC)
Repository:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/370786
Online Access:http://hdl.handle.net/10261/370786
Access Level:Open access
Keyword:Boron carrier
Metallacarborane
Na[o-COSAN]
Biodistribution studies
Boron neutron capture therapy
BNCT
Head and neck cancer
Hamster
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spelling Cobaltabis(Dicarbollide) [o-COSAN]− for Boron Neutron Capture Therapy of Head and Neck Cancer: Biodistribution and Irradiation Studies in an Experimental Oral Cancer ModelPalmieri, Mónica A.Monti Hughes, AndreaTrivillin, Verónica A.Garabalino, Marcela A.Ramos, Paula S.Thorp, Silvia I.Curotto, PaulaPozzi, Emiliano C. C.Nuez Martínez, MiquelTeixidor, FrancescViñas, ClaraSchwint, Amanda E.Boron carrierMetallacarboraneNa[o-COSAN]Biodistribution studiesBoron neutron capture therapyBNCTHead and neck cancerHamsterBackground: Boron neutron capture therapy (BNCT) is a tumor-selective particle radiotherapy that combines preferential boron accumulation in tumors and neutron irradiation. Based on previous studies in tumor-bearing mice, this study evaluated the biodistribution of the sodium salt of cobaltabis(dicarbollide) (Na[3,3′-Co(C2B9H11)2], abbreviated as Na[o-COSAN]) in the hamster cheek pouch oral cancer model and the Na[o-COSAN]/BNCT therapeutic effect on tumors and induced radiotoxicity. The synthesis and comprehensive characterization of 10B-enriched trimethylammonium salt of nido-[7,8-C2 10B9H12]−o-carborane, along with the cesium and sodium salts of [o-10COSAN] cobaltabis(dicarbollide) are reported here for the first time. Methods: Hamsters bearing tumors were injected with Na[o-COSAN] (7.5 mg B/kg) and euthanized at different timepoints after injection (30 min, 2, 3, 5, and 18 h post-administration) to evaluate boron uptake in different tissues/organs. Based on these results, tumor-bearing animals were treated with Na[10B-o-COSAN]/BNCT (7.5 mg B/kg b.w., 3 h), prescribing 5 Gy total in absorbed dose to the precancerous tissue surrounding tumors, i.e., the dose-limiting tissue. Results: Na[o-10COSAN] exhibited no toxicity. Although biodistribution studies employing Na[o-COSAN] have shown low absolute boron concentration in the tumor (approx. 11 ppm), Na[o-10COSAN]/BNCT induced a high and significant therapeutic effect on tumors versus the control group (cancerized, untreated animals). Moreover, only half of the animals exhibited severe mucositis in the precancerous dose-limiting tissue after BNCT, which resolved completely at 21 days after irradiation. Conclusions: Na[o-10COSAN] would be potentially useful to treat head and neck cancer with BNCT.This research was funded by the National Atomic Energy Commission from Argentina, the Spanish Ministry of Economy and Competitiveness (PID2019-106832RB-I00), and the Generalitat of Catalunya (2017SGR1720).Peer reviewedMultidisciplinary Digital Publishing InstituteComisión Nacional de Energía Atómica (Argentina)Ministerio de Economía y Competitividad (España)Generalitat de CatalunyaConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2024202420242024info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/370786reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-106832RB-I00The underlying dataset has been published as supplementary material of the article in the publisher platform at DOI https://doi.org/10.3390/ph17101367https://doi.org/10.3390/ph17101367Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3707862026-05-22T06:33:51Z
dc.title.none.fl_str_mv Cobaltabis(Dicarbollide) [o-COSAN]− for Boron Neutron Capture Therapy of Head and Neck Cancer: Biodistribution and Irradiation Studies in an Experimental Oral Cancer Model
title Cobaltabis(Dicarbollide) [o-COSAN]− for Boron Neutron Capture Therapy of Head and Neck Cancer: Biodistribution and Irradiation Studies in an Experimental Oral Cancer Model
spellingShingle Cobaltabis(Dicarbollide) [o-COSAN]− for Boron Neutron Capture Therapy of Head and Neck Cancer: Biodistribution and Irradiation Studies in an Experimental Oral Cancer Model
Palmieri, Mónica A.
Boron carrier
Metallacarborane
Na[o-COSAN]
Biodistribution studies
Boron neutron capture therapy
BNCT
Head and neck cancer
Hamster
title_short Cobaltabis(Dicarbollide) [o-COSAN]− for Boron Neutron Capture Therapy of Head and Neck Cancer: Biodistribution and Irradiation Studies in an Experimental Oral Cancer Model
title_full Cobaltabis(Dicarbollide) [o-COSAN]− for Boron Neutron Capture Therapy of Head and Neck Cancer: Biodistribution and Irradiation Studies in an Experimental Oral Cancer Model
title_fullStr Cobaltabis(Dicarbollide) [o-COSAN]− for Boron Neutron Capture Therapy of Head and Neck Cancer: Biodistribution and Irradiation Studies in an Experimental Oral Cancer Model
title_full_unstemmed Cobaltabis(Dicarbollide) [o-COSAN]− for Boron Neutron Capture Therapy of Head and Neck Cancer: Biodistribution and Irradiation Studies in an Experimental Oral Cancer Model
title_sort Cobaltabis(Dicarbollide) [o-COSAN]− for Boron Neutron Capture Therapy of Head and Neck Cancer: Biodistribution and Irradiation Studies in an Experimental Oral Cancer Model
dc.creator.none.fl_str_mv Palmieri, Mónica A.
Monti Hughes, Andrea
Trivillin, Verónica A.
Garabalino, Marcela A.
Ramos, Paula S.
Thorp, Silvia I.
Curotto, Paula
Pozzi, Emiliano C. C.
Nuez Martínez, Miquel
Teixidor, Francesc
Viñas, Clara
Schwint, Amanda E.
author Palmieri, Mónica A.
author_facet Palmieri, Mónica A.
Monti Hughes, Andrea
Trivillin, Verónica A.
Garabalino, Marcela A.
Ramos, Paula S.
Thorp, Silvia I.
Curotto, Paula
Pozzi, Emiliano C. C.
Nuez Martínez, Miquel
Teixidor, Francesc
Viñas, Clara
Schwint, Amanda E.
author_role author
author2 Monti Hughes, Andrea
Trivillin, Verónica A.
Garabalino, Marcela A.
Ramos, Paula S.
Thorp, Silvia I.
Curotto, Paula
Pozzi, Emiliano C. C.
Nuez Martínez, Miquel
Teixidor, Francesc
Viñas, Clara
Schwint, Amanda E.
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Comisión Nacional de Energía Atómica (Argentina)
Ministerio de Economía y Competitividad (España)
Generalitat de Catalunya
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Boron carrier
Metallacarborane
Na[o-COSAN]
Biodistribution studies
Boron neutron capture therapy
BNCT
Head and neck cancer
Hamster
topic Boron carrier
Metallacarborane
Na[o-COSAN]
Biodistribution studies
Boron neutron capture therapy
BNCT
Head and neck cancer
Hamster
description Background: Boron neutron capture therapy (BNCT) is a tumor-selective particle radiotherapy that combines preferential boron accumulation in tumors and neutron irradiation. Based on previous studies in tumor-bearing mice, this study evaluated the biodistribution of the sodium salt of cobaltabis(dicarbollide) (Na[3,3′-Co(C2B9H11)2], abbreviated as Na[o-COSAN]) in the hamster cheek pouch oral cancer model and the Na[o-COSAN]/BNCT therapeutic effect on tumors and induced radiotoxicity. The synthesis and comprehensive characterization of 10B-enriched trimethylammonium salt of nido-[7,8-C2 10B9H12]−o-carborane, along with the cesium and sodium salts of [o-10COSAN] cobaltabis(dicarbollide) are reported here for the first time. Methods: Hamsters bearing tumors were injected with Na[o-COSAN] (7.5 mg B/kg) and euthanized at different timepoints after injection (30 min, 2, 3, 5, and 18 h post-administration) to evaluate boron uptake in different tissues/organs. Based on these results, tumor-bearing animals were treated with Na[10B-o-COSAN]/BNCT (7.5 mg B/kg b.w., 3 h), prescribing 5 Gy total in absorbed dose to the precancerous tissue surrounding tumors, i.e., the dose-limiting tissue. Results: Na[o-10COSAN] exhibited no toxicity. Although biodistribution studies employing Na[o-COSAN] have shown low absolute boron concentration in the tumor (approx. 11 ppm), Na[o-10COSAN]/BNCT induced a high and significant therapeutic effect on tumors versus the control group (cancerized, untreated animals). Moreover, only half of the animals exhibited severe mucositis in the precancerous dose-limiting tissue after BNCT, which resolved completely at 21 days after irradiation. Conclusions: Na[o-10COSAN] would be potentially useful to treat head and neck cancer with BNCT.
publishDate 2024
dc.date.none.fl_str_mv 2024
2024
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/370786
url http://hdl.handle.net/10261/370786
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-106832RB-I00
The underlying dataset has been published as supplementary material of the article in the publisher platform at DOI https://doi.org/10.3390/ph17101367
https://doi.org/10.3390/ph17101367
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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