Tumor blood vessel ''normalization'' improves the therapeutic efficacy of boron neutron capture therapy (BNCT) in experimental oral cancer

Autores
Molinari, Ana Julia; Pozzi, Emiliano César Cayetano; Monti Hughes, Andrea; Heber, Elisa Mercedes; Garabalino, Marcela Alejandra; Thorp, Silvia Inés; Miller, Marcelo Eduardo; Itoiz, María Elina; Aromando, Romina Flavia; Nigg, David W.; Trivillin, Verónica Andrea; Schwint, Amanda Elena
Año de publicación
2011
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
We previously demonstrated the efficacy of BNCT mediated by boronophenylalanine (BPA) to treat tumors in a hamster cheek pouch model of oral cancer with no normal tissue radiotoxicity and moderate, albeit reversible, mucositis in precancerous tissue around treated tumors. It is known that boron targeting of the largest possible proportion of tumor cells contributes to the success of BNCT and that tumor blood vessel normalization improves drug delivery to the tumor. Within this context, the aim of the present study was to evaluate the effect of blood vessel normalization on the therapeutic efficacy and potential radiotoxicity of BNCT in the hamster cheek pouch model of oral cancer. Blood vessel normalization was induced by two doses of thalidomide in tumor-bearing hamsters on 2 consecutive days. All studies in thalidomide-treated animals were performed 48 h after the first dose of thalidomide, previously established as the window of normalization. Biodistribution studies were performed with BPA at a dose of 15.5 mg 10B/kg in thalidomide-treated (Th+) and untreated (Th–) tumorbearing hamsters. The effect of blood vessel normalization prior to BPA administration on the efficacy of BNCT was assessed in in vivo BNCT studies at the RA-3 Nuclear Reactor in tumor-bearing hamsters. Group I was treated with BPABNCT after treatment with thalidomide (Th+ BPA-BNCT). Group II was treated with BPA-BNCT alone (Th– BPABNCT). Group III was treated with the beam only after treatment with thalidomide (Th+ BO), and Group IV was treated with the beam only (Th– BO). Groups I and II were given the same dose of BPA (15.5 mg 10B/kg), and all groups (I–IV) were exposed to the same neutron fluence. Two additional groups were treated with the beam only at a higher dose to exacerbate mucositis in precancerous tissue and to explore the potential direct protective effect of thalidomide on radiation-induced mucositis in a scenario of more severe toxicity, i.e. Group V (Th+ hdBO) and Group VI (Th– hdBO). The animals were followed for 28 days. Biodistribution studies revealed no statistically significant differences in gross boron content between Th+ and Th– animals. Overall tumor control (complete response + partial response) at 28 days post-treatment was significantly higher for Group I (Th+ BPA-BNCT) than for Group II (Th– BPA-BNCT): 84 6 3% compared to 67 6 5%. Pretreatment with thalidomide did not induce statistically significant changes in overall tumor control induced by the beam only, i.e. 15 6 5% in Group III (Th+ BO) and 18 6 5% in Group IV (Th– BO), or in overall tumor control induced by the high-dose beam only, i.e. 60 6 7% in Group V (Th+ hdBO) and 47 6 10% in Group VI (Th– hdBO). BPA-BNCT alone (Group II) induced mucositis in precancerous tissue that reached Grades 3–4 in 80% of the animals, whereas pretreatment with thalidomide (Group I) prevented mucositis Grades 3 and 4 completely. Beam-only Group III (Th+ BO) exhibited only Grade 1 mucositis in precancerous tissue, whereas 17% of the animals in beamonly Group IV (Th– BO) reached Grade 2 mucositis. Highdose beam-only group V (Th+ hdBO) exhibited only Grade 2 mucositis, whereas high-dose beam-only group VI (Th– hdBO) reached Grade 3 mucositis in 83% of the animals. In all cases mucositis in precancerous tissue was reversible. No normal tissue radiotoxicity was observed with any of the protocols. Pretreatment with thalidomide enhanced the therapeutic efficacy of BNCT and reduced precancerous tissue toxicity.
Fil: Molinari, Ana Julia. Comisión Nacional de Energía Atómica. Gerencia de Área de Aplicaciones de la Tecnología Nuclear. Departamento de Radiobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Pozzi, Emiliano César Cayetano. Comisión Nacional de Energía Atómica. Gerencia de Área de Aplicaciones de la Tecnología Nuclear. Departamento de Radiobiología; Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Ezeiza; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Monti Hughes, Andrea. Comisión Nacional de Energía Atómica. Gerencia de Área de Aplicaciones de la Tecnología Nuclear. Departamento de Radiobiología; Argentina
Fil: Heber, Elisa Mercedes. Comisión Nacional de Energía Atómica. Gerencia de Área de Aplicaciones de la Tecnología Nuclear. Departamento de Radiobiología; Argentina
Fil: Garabalino, Marcela Alejandra. Comisión Nacional de Energía Atómica. Gerencia de Área de Aplicaciones de la Tecnología Nuclear. Departamento de Radiobiología; Argentina
Fil: Thorp, Silvia Inés. Comisión Nacional de Energía Atómica. Centro Atómico Ezeiza; Argentina
Fil: Miller, Marcelo Eduardo. Comisión Nacional de Energía Atómica. Centro Atómico Ezeiza; Argentina
Fil: Itoiz, María Elina. Comisión Nacional de Energía Atómica. Gerencia de Área de Aplicaciones de la Tecnología Nuclear. Departamento de Radiobiología; Argentina. Universidad de Buenos Aires. Facultad de Odontología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Aromando, Romina Flavia. Universidad de Buenos Aires. Facultad de Odontología; Argentina
Fil: Nigg, David W.. Idaho National Laboratory; Estados Unidos
Fil: Trivillin, Verónica Andrea. Comisión Nacional de Energía Atómica. Gerencia de Área de Aplicaciones de la Tecnología Nuclear. Departamento de Radiobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Schwint, Amanda Elena. Comisión Nacional de Energía Atómica. Gerencia de Área de Aplicaciones de la Tecnología Nuclear. Departamento de Radiobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
Tumor Blood Vessel
Boron Neutron Capture Therapy
Oral Cancer
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/194547
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/194547
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repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Tumor blood vessel ''normalization'' improves the therapeutic efficacy of boron neutron capture therapy (BNCT) in experimental oral cancerMolinari, Ana JuliaPozzi, Emiliano César CayetanoMonti Hughes, AndreaHeber, Elisa MercedesGarabalino, Marcela AlejandraThorp, Silvia InésMiller, Marcelo EduardoItoiz, María ElinaAromando, Romina FlaviaNigg, David W.Trivillin, Verónica AndreaSchwint, Amanda ElenaTumor Blood VesselBoron Neutron Capture TherapyOral Cancerhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3We previously demonstrated the efficacy of BNCT mediated by boronophenylalanine (BPA) to treat tumors in a hamster cheek pouch model of oral cancer with no normal tissue radiotoxicity and moderate, albeit reversible, mucositis in precancerous tissue around treated tumors. It is known that boron targeting of the largest possible proportion of tumor cells contributes to the success of BNCT and that tumor blood vessel normalization improves drug delivery to the tumor. Within this context, the aim of the present study was to evaluate the effect of blood vessel normalization on the therapeutic efficacy and potential radiotoxicity of BNCT in the hamster cheek pouch model of oral cancer. Blood vessel normalization was induced by two doses of thalidomide in tumor-bearing hamsters on 2 consecutive days. All studies in thalidomide-treated animals were performed 48 h after the first dose of thalidomide, previously established as the window of normalization. Biodistribution studies were performed with BPA at a dose of 15.5 mg 10B/kg in thalidomide-treated (Th+) and untreated (Th–) tumorbearing hamsters. The effect of blood vessel normalization prior to BPA administration on the efficacy of BNCT was assessed in in vivo BNCT studies at the RA-3 Nuclear Reactor in tumor-bearing hamsters. Group I was treated with BPABNCT after treatment with thalidomide (Th+ BPA-BNCT). Group II was treated with BPA-BNCT alone (Th– BPABNCT). Group III was treated with the beam only after treatment with thalidomide (Th+ BO), and Group IV was treated with the beam only (Th– BO). Groups I and II were given the same dose of BPA (15.5 mg 10B/kg), and all groups (I–IV) were exposed to the same neutron fluence. Two additional groups were treated with the beam only at a higher dose to exacerbate mucositis in precancerous tissue and to explore the potential direct protective effect of thalidomide on radiation-induced mucositis in a scenario of more severe toxicity, i.e. Group V (Th+ hdBO) and Group VI (Th– hdBO). The animals were followed for 28 days. Biodistribution studies revealed no statistically significant differences in gross boron content between Th+ and Th– animals. Overall tumor control (complete response + partial response) at 28 days post-treatment was significantly higher for Group I (Th+ BPA-BNCT) than for Group II (Th– BPA-BNCT): 84 6 3% compared to 67 6 5%. Pretreatment with thalidomide did not induce statistically significant changes in overall tumor control induced by the beam only, i.e. 15 6 5% in Group III (Th+ BO) and 18 6 5% in Group IV (Th– BO), or in overall tumor control induced by the high-dose beam only, i.e. 60 6 7% in Group V (Th+ hdBO) and 47 6 10% in Group VI (Th– hdBO). BPA-BNCT alone (Group II) induced mucositis in precancerous tissue that reached Grades 3–4 in 80% of the animals, whereas pretreatment with thalidomide (Group I) prevented mucositis Grades 3 and 4 completely. Beam-only Group III (Th+ BO) exhibited only Grade 1 mucositis in precancerous tissue, whereas 17% of the animals in beamonly Group IV (Th– BO) reached Grade 2 mucositis. Highdose beam-only group V (Th+ hdBO) exhibited only Grade 2 mucositis, whereas high-dose beam-only group VI (Th– hdBO) reached Grade 3 mucositis in 83% of the animals. In all cases mucositis in precancerous tissue was reversible. No normal tissue radiotoxicity was observed with any of the protocols. Pretreatment with thalidomide enhanced the therapeutic efficacy of BNCT and reduced precancerous tissue toxicity.Fil: Molinari, Ana Julia. Comisión Nacional de Energía Atómica. Gerencia de Área de Aplicaciones de la Tecnología Nuclear. Departamento de Radiobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Pozzi, Emiliano César Cayetano. Comisión Nacional de Energía Atómica. Gerencia de Área de Aplicaciones de la Tecnología Nuclear. Departamento de Radiobiología; Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Ezeiza; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Monti Hughes, Andrea. Comisión Nacional de Energía Atómica. Gerencia de Área de Aplicaciones de la Tecnología Nuclear. Departamento de Radiobiología; ArgentinaFil: Heber, Elisa Mercedes. Comisión Nacional de Energía Atómica. Gerencia de Área de Aplicaciones de la Tecnología Nuclear. Departamento de Radiobiología; ArgentinaFil: Garabalino, Marcela Alejandra. Comisión Nacional de Energía Atómica. Gerencia de Área de Aplicaciones de la Tecnología Nuclear. Departamento de Radiobiología; ArgentinaFil: Thorp, Silvia Inés. Comisión Nacional de Energía Atómica. Centro Atómico Ezeiza; ArgentinaFil: Miller, Marcelo Eduardo. Comisión Nacional de Energía Atómica. Centro Atómico Ezeiza; ArgentinaFil: Itoiz, María Elina. Comisión Nacional de Energía Atómica. Gerencia de Área de Aplicaciones de la Tecnología Nuclear. Departamento de Radiobiología; Argentina. Universidad de Buenos Aires. Facultad de Odontología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Aromando, Romina Flavia. Universidad de Buenos Aires. Facultad de Odontología; ArgentinaFil: Nigg, David W.. Idaho National Laboratory; Estados UnidosFil: Trivillin, Verónica Andrea. Comisión Nacional de Energía Atómica. Gerencia de Área de Aplicaciones de la Tecnología Nuclear. Departamento de Radiobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Schwint, Amanda Elena. Comisión Nacional de Energía Atómica. Gerencia de Área de Aplicaciones de la Tecnología Nuclear. Departamento de Radiobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaRadiation Research Soc2011-10-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/194547Molinari, Ana Julia; Pozzi, Emiliano César Cayetano; Monti Hughes, Andrea; Heber, Elisa Mercedes; Garabalino, Marcela Alejandra; et al.; Tumor blood vessel ''normalization'' improves the therapeutic efficacy of boron neutron capture therapy (BNCT) in experimental oral cancer; Radiation Research Soc; Radiation Research; 177; 1; 10-10-2011; 59-680033-75871938-5404CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://bioone.org/journals/radiation-research/volume-177/issue-1/RR2729.1/Tumor-Blood-Vessel-Normalization-Improves-the-Therapeutic-Efficacy-of-Boron/10.1667/RR2729.1.shortinfo:eu-repo/semantics/altIdentifier/doi/ 10.1667/RR2729.1info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:55:18Zoai:ri.conicet.gov.ar:11336/194547instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:55:19.006CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Tumor blood vessel ''normalization'' improves the therapeutic efficacy of boron neutron capture therapy (BNCT) in experimental oral cancer
title Tumor blood vessel ''normalization'' improves the therapeutic efficacy of boron neutron capture therapy (BNCT) in experimental oral cancer
spellingShingle Tumor blood vessel ''normalization'' improves the therapeutic efficacy of boron neutron capture therapy (BNCT) in experimental oral cancer
Molinari, Ana Julia
Tumor Blood Vessel
Boron Neutron Capture Therapy
Oral Cancer
title_short Tumor blood vessel ''normalization'' improves the therapeutic efficacy of boron neutron capture therapy (BNCT) in experimental oral cancer
title_full Tumor blood vessel ''normalization'' improves the therapeutic efficacy of boron neutron capture therapy (BNCT) in experimental oral cancer
title_fullStr Tumor blood vessel ''normalization'' improves the therapeutic efficacy of boron neutron capture therapy (BNCT) in experimental oral cancer
title_full_unstemmed Tumor blood vessel ''normalization'' improves the therapeutic efficacy of boron neutron capture therapy (BNCT) in experimental oral cancer
title_sort Tumor blood vessel ''normalization'' improves the therapeutic efficacy of boron neutron capture therapy (BNCT) in experimental oral cancer
dc.creator.none.fl_str_mv Molinari, Ana Julia
Pozzi, Emiliano César Cayetano
Monti Hughes, Andrea
Heber, Elisa Mercedes
Garabalino, Marcela Alejandra
Thorp, Silvia Inés
Miller, Marcelo Eduardo
Itoiz, María Elina
Aromando, Romina Flavia
Nigg, David W.
Trivillin, Verónica Andrea
Schwint, Amanda Elena
author Molinari, Ana Julia
author_facet Molinari, Ana Julia
Pozzi, Emiliano César Cayetano
Monti Hughes, Andrea
Heber, Elisa Mercedes
Garabalino, Marcela Alejandra
Thorp, Silvia Inés
Miller, Marcelo Eduardo
Itoiz, María Elina
Aromando, Romina Flavia
Nigg, David W.
Trivillin, Verónica Andrea
Schwint, Amanda Elena
author_role author
author2 Pozzi, Emiliano César Cayetano
Monti Hughes, Andrea
Heber, Elisa Mercedes
Garabalino, Marcela Alejandra
Thorp, Silvia Inés
Miller, Marcelo Eduardo
Itoiz, María Elina
Aromando, Romina Flavia
Nigg, David W.
Trivillin, Verónica Andrea
Schwint, Amanda Elena
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Tumor Blood Vessel
Boron Neutron Capture Therapy
Oral Cancer
topic Tumor Blood Vessel
Boron Neutron Capture Therapy
Oral Cancer
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv We previously demonstrated the efficacy of BNCT mediated by boronophenylalanine (BPA) to treat tumors in a hamster cheek pouch model of oral cancer with no normal tissue radiotoxicity and moderate, albeit reversible, mucositis in precancerous tissue around treated tumors. It is known that boron targeting of the largest possible proportion of tumor cells contributes to the success of BNCT and that tumor blood vessel normalization improves drug delivery to the tumor. Within this context, the aim of the present study was to evaluate the effect of blood vessel normalization on the therapeutic efficacy and potential radiotoxicity of BNCT in the hamster cheek pouch model of oral cancer. Blood vessel normalization was induced by two doses of thalidomide in tumor-bearing hamsters on 2 consecutive days. All studies in thalidomide-treated animals were performed 48 h after the first dose of thalidomide, previously established as the window of normalization. Biodistribution studies were performed with BPA at a dose of 15.5 mg 10B/kg in thalidomide-treated (Th+) and untreated (Th–) tumorbearing hamsters. The effect of blood vessel normalization prior to BPA administration on the efficacy of BNCT was assessed in in vivo BNCT studies at the RA-3 Nuclear Reactor in tumor-bearing hamsters. Group I was treated with BPABNCT after treatment with thalidomide (Th+ BPA-BNCT). Group II was treated with BPA-BNCT alone (Th– BPABNCT). Group III was treated with the beam only after treatment with thalidomide (Th+ BO), and Group IV was treated with the beam only (Th– BO). Groups I and II were given the same dose of BPA (15.5 mg 10B/kg), and all groups (I–IV) were exposed to the same neutron fluence. Two additional groups were treated with the beam only at a higher dose to exacerbate mucositis in precancerous tissue and to explore the potential direct protective effect of thalidomide on radiation-induced mucositis in a scenario of more severe toxicity, i.e. Group V (Th+ hdBO) and Group VI (Th– hdBO). The animals were followed for 28 days. Biodistribution studies revealed no statistically significant differences in gross boron content between Th+ and Th– animals. Overall tumor control (complete response + partial response) at 28 days post-treatment was significantly higher for Group I (Th+ BPA-BNCT) than for Group II (Th– BPA-BNCT): 84 6 3% compared to 67 6 5%. Pretreatment with thalidomide did not induce statistically significant changes in overall tumor control induced by the beam only, i.e. 15 6 5% in Group III (Th+ BO) and 18 6 5% in Group IV (Th– BO), or in overall tumor control induced by the high-dose beam only, i.e. 60 6 7% in Group V (Th+ hdBO) and 47 6 10% in Group VI (Th– hdBO). BPA-BNCT alone (Group II) induced mucositis in precancerous tissue that reached Grades 3–4 in 80% of the animals, whereas pretreatment with thalidomide (Group I) prevented mucositis Grades 3 and 4 completely. Beam-only Group III (Th+ BO) exhibited only Grade 1 mucositis in precancerous tissue, whereas 17% of the animals in beamonly Group IV (Th– BO) reached Grade 2 mucositis. Highdose beam-only group V (Th+ hdBO) exhibited only Grade 2 mucositis, whereas high-dose beam-only group VI (Th– hdBO) reached Grade 3 mucositis in 83% of the animals. In all cases mucositis in precancerous tissue was reversible. No normal tissue radiotoxicity was observed with any of the protocols. Pretreatment with thalidomide enhanced the therapeutic efficacy of BNCT and reduced precancerous tissue toxicity.
Fil: Molinari, Ana Julia. Comisión Nacional de Energía Atómica. Gerencia de Área de Aplicaciones de la Tecnología Nuclear. Departamento de Radiobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Pozzi, Emiliano César Cayetano. Comisión Nacional de Energía Atómica. Gerencia de Área de Aplicaciones de la Tecnología Nuclear. Departamento de Radiobiología; Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Ezeiza; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Monti Hughes, Andrea. Comisión Nacional de Energía Atómica. Gerencia de Área de Aplicaciones de la Tecnología Nuclear. Departamento de Radiobiología; Argentina
Fil: Heber, Elisa Mercedes. Comisión Nacional de Energía Atómica. Gerencia de Área de Aplicaciones de la Tecnología Nuclear. Departamento de Radiobiología; Argentina
Fil: Garabalino, Marcela Alejandra. Comisión Nacional de Energía Atómica. Gerencia de Área de Aplicaciones de la Tecnología Nuclear. Departamento de Radiobiología; Argentina
Fil: Thorp, Silvia Inés. Comisión Nacional de Energía Atómica. Centro Atómico Ezeiza; Argentina
Fil: Miller, Marcelo Eduardo. Comisión Nacional de Energía Atómica. Centro Atómico Ezeiza; Argentina
Fil: Itoiz, María Elina. Comisión Nacional de Energía Atómica. Gerencia de Área de Aplicaciones de la Tecnología Nuclear. Departamento de Radiobiología; Argentina. Universidad de Buenos Aires. Facultad de Odontología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Aromando, Romina Flavia. Universidad de Buenos Aires. Facultad de Odontología; Argentina
Fil: Nigg, David W.. Idaho National Laboratory; Estados Unidos
Fil: Trivillin, Verónica Andrea. Comisión Nacional de Energía Atómica. Gerencia de Área de Aplicaciones de la Tecnología Nuclear. Departamento de Radiobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Schwint, Amanda Elena. Comisión Nacional de Energía Atómica. Gerencia de Área de Aplicaciones de la Tecnología Nuclear. Departamento de Radiobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description We previously demonstrated the efficacy of BNCT mediated by boronophenylalanine (BPA) to treat tumors in a hamster cheek pouch model of oral cancer with no normal tissue radiotoxicity and moderate, albeit reversible, mucositis in precancerous tissue around treated tumors. It is known that boron targeting of the largest possible proportion of tumor cells contributes to the success of BNCT and that tumor blood vessel normalization improves drug delivery to the tumor. Within this context, the aim of the present study was to evaluate the effect of blood vessel normalization on the therapeutic efficacy and potential radiotoxicity of BNCT in the hamster cheek pouch model of oral cancer. Blood vessel normalization was induced by two doses of thalidomide in tumor-bearing hamsters on 2 consecutive days. All studies in thalidomide-treated animals were performed 48 h after the first dose of thalidomide, previously established as the window of normalization. Biodistribution studies were performed with BPA at a dose of 15.5 mg 10B/kg in thalidomide-treated (Th+) and untreated (Th–) tumorbearing hamsters. The effect of blood vessel normalization prior to BPA administration on the efficacy of BNCT was assessed in in vivo BNCT studies at the RA-3 Nuclear Reactor in tumor-bearing hamsters. Group I was treated with BPABNCT after treatment with thalidomide (Th+ BPA-BNCT). Group II was treated with BPA-BNCT alone (Th– BPABNCT). Group III was treated with the beam only after treatment with thalidomide (Th+ BO), and Group IV was treated with the beam only (Th– BO). Groups I and II were given the same dose of BPA (15.5 mg 10B/kg), and all groups (I–IV) were exposed to the same neutron fluence. Two additional groups were treated with the beam only at a higher dose to exacerbate mucositis in precancerous tissue and to explore the potential direct protective effect of thalidomide on radiation-induced mucositis in a scenario of more severe toxicity, i.e. Group V (Th+ hdBO) and Group VI (Th– hdBO). The animals were followed for 28 days. Biodistribution studies revealed no statistically significant differences in gross boron content between Th+ and Th– animals. Overall tumor control (complete response + partial response) at 28 days post-treatment was significantly higher for Group I (Th+ BPA-BNCT) than for Group II (Th– BPA-BNCT): 84 6 3% compared to 67 6 5%. Pretreatment with thalidomide did not induce statistically significant changes in overall tumor control induced by the beam only, i.e. 15 6 5% in Group III (Th+ BO) and 18 6 5% in Group IV (Th– BO), or in overall tumor control induced by the high-dose beam only, i.e. 60 6 7% in Group V (Th+ hdBO) and 47 6 10% in Group VI (Th– hdBO). BPA-BNCT alone (Group II) induced mucositis in precancerous tissue that reached Grades 3–4 in 80% of the animals, whereas pretreatment with thalidomide (Group I) prevented mucositis Grades 3 and 4 completely. Beam-only Group III (Th+ BO) exhibited only Grade 1 mucositis in precancerous tissue, whereas 17% of the animals in beamonly Group IV (Th– BO) reached Grade 2 mucositis. Highdose beam-only group V (Th+ hdBO) exhibited only Grade 2 mucositis, whereas high-dose beam-only group VI (Th– hdBO) reached Grade 3 mucositis in 83% of the animals. In all cases mucositis in precancerous tissue was reversible. No normal tissue radiotoxicity was observed with any of the protocols. Pretreatment with thalidomide enhanced the therapeutic efficacy of BNCT and reduced precancerous tissue toxicity.
publishDate 2011
dc.date.none.fl_str_mv 2011-10-10
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/194547
Molinari, Ana Julia; Pozzi, Emiliano César Cayetano; Monti Hughes, Andrea; Heber, Elisa Mercedes; Garabalino, Marcela Alejandra; et al.; Tumor blood vessel ''normalization'' improves the therapeutic efficacy of boron neutron capture therapy (BNCT) in experimental oral cancer; Radiation Research Soc; Radiation Research; 177; 1; 10-10-2011; 59-68
0033-7587
1938-5404
CONICET Digital
CONICET
url http://hdl.handle.net/11336/194547
identifier_str_mv Molinari, Ana Julia; Pozzi, Emiliano César Cayetano; Monti Hughes, Andrea; Heber, Elisa Mercedes; Garabalino, Marcela Alejandra; et al.; Tumor blood vessel ''normalization'' improves the therapeutic efficacy of boron neutron capture therapy (BNCT) in experimental oral cancer; Radiation Research Soc; Radiation Research; 177; 1; 10-10-2011; 59-68
0033-7587
1938-5404
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://bioone.org/journals/radiation-research/volume-177/issue-1/RR2729.1/Tumor-Blood-Vessel-Normalization-Improves-the-Therapeutic-Efficacy-of-Boron/10.1667/RR2729.1.short
info:eu-repo/semantics/altIdentifier/doi/ 10.1667/RR2729.1
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dc.publisher.none.fl_str_mv Radiation Research Soc
publisher.none.fl_str_mv Radiation Research Soc
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reponame_str CONICET Digital (CONICET)
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instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1844613668555194368
score 13.070432

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