Toward a clinical application of ex situ boron neutron capture therapy for lung tumors at the RA-3 reactor in Argentina
- Autores
- Farías, Rubén Oscar; Garabalino, Marcela Alejandra; Ferraris, Sergio; Santa María, Juan; Rovati, Osvaldo Daniel; Lange, Fernando; Trivillin, Verónica Andrea; Monti Hughes, Andrea; Pozzi, Emiliano César Cayetano; Thorp, Silvia Inés; Curotto, Paula; Boltolussi, S.; Altieri, S.; Portu, Agustina Mariana; Saint Martin, María Laura Gisela; Schwint, Amanda Elena; González, Sara Josefina
- Año de publicación
- 2015
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Purpose: Many types of lung tumors have a very poor prognosis due to their spread in the whole organ volume. The fact that boron neutron capture therapy (BNCT) would allow for selective targeting of all the nodules regardless of their position, prompted a preclinical feasibility study of ex situ BNCT at the thermal neutron facility of RA‐3 reactor in the province of Buenos Aires, Argentina. (l)‐4p‐dihydroxy‐borylphenylalanine fructose complex (BPA‐F) biodistribution studies in an adult sheep model and computational dosimetry for a human explanted lung were performed to evaluate the feasibility and the therapeutic potential of ex situ BNCT. Methods: Two kinds of boron biodistribution studies were carried out in the healthy sheep: a set of pharmacokinetic studies without lung excision, and a set that consisted of evaluation of boron concentration in the explanted and perfused lung. In order to assess the feasibility of the clinical application of ex situ BNCT at RA‐3, a case of multiple lung metastases was analyzed. A detailed computational representation of the geometry of the lung was built based on a real collapsed human lung. Dosimetric calculations and dose limiting considerations were based on the experimental results from the adult sheep, and on the most suitable information published in the literature. In addition, a workable treatment plan was considered to assess the clinical application in a realistic scenario. Results: Concentration‐time profiles for the normal sheep showed that the boron kinetics in blood, lung, and skin would adequately represent the boron behavior and absolute uptake expected in human tissues. Results strongly suggest that the distribution of the boron compound is spatially homogeneous in the lung. A constant lung‐to‐blood ratio of 1.3 ± 0.1 was observed from 80 min after the end of BPA‐F infusion. The fact that this ratio remains constant during time would allow the blood boron concentration to be used as a surrogate and indirect quantification of the estimated value in the explanted healthy lung. The proposed preclinical animal model allowed for the study of the explanted lung. As expected, the boron concentration values fell as a result of the application of the preservation protocol required to preserve the lung function. The distribution of the boron concentration retention factor was obtained for healthy lung, with a mean value of 0.46 ± 0.14 consistent with that reported for metastatic colon carcinoma model in rat perfused lung. Considering the human lung model and suitable tumor control probability for lung cancer, a promising average fraction of controlled lesions higher than 85% was obtained even for a low tumor‐to‐normal boron concentration ratio of 2. Conclusions: This work reports for the first time data supporting the validity of the ovine model as an adequate human surrogate in terms of boron kinetics and uptake in clinically relevant tissues. Collectively, the results and analysis presented would strongly suggest that ex situ whole lung BNCT irradiation is a feasible and highly promising technique that could greatly contribute to the treatment of metastatic lung disease in those patients without extrapulmonary spread, increasing not only the expected overall survival but also the resulting quality of life.
Fil: Farías, Rubén Oscar. Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Gerencia de Radiobiología (Centro Atómico Constituyentes); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Garabalino, Marcela Alejandra. Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Gerencia de Radiobiología (Centro Atómico Constituyentes); Argentina
Fil: Ferraris, Sergio. Universidad Maimónides; Argentina
Fil: Santa María, Juan. Universidad Maimónides; Argentina
Fil: Rovati, Osvaldo Daniel. Universidad Maimónides; Argentina
Fil: Lange, Fernando. Universidad Maimónides; Argentina
Fil: Trivillin, Verónica Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Gerencia de Radiobiología (Centro Atómico Constituyentes); Argentina
Fil: Monti Hughes, Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Gerencia de Radiobiología (Centro Atómico Constituyentes); Argentina
Fil: Pozzi, Emiliano César Cayetano. Comisión Nacional de Energía Atómica; Argentina
Fil: Thorp, Silvia Inés. Comisión Nacional de Energía Atómica; Argentina
Fil: Curotto, Paula. Comisión Nacional de Energía Atómica; Argentina
Fil: Boltolussi, S. Istituto Nazionale Di Fisica Nucleare; Italia
Fil: Altieri, S.. Istituto Nazionale Di Fisica Nucleare; Italia. Università Di Pavia; Italia
Fil: Portu, Agustina Mariana. Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Gerencia de Radiobiología (Centro Atómico Constituyentes); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Saint Martin, María Laura Gisela. Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Gerencia de Radiobiología (Centro Atómico Constituyentes); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Schwint, Amanda Elena. Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Gerencia de Radiobiología (Centro Atómico Constituyentes); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: González, Sara Josefina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; Argentina - Materia
-
Bnct
Ex Situ Irradiation
Lung Tumors
Bpa-F
Pharmacokinetics - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
.jpg)
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/41775
Ver los metadatos del registro completo
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Toward a clinical application of ex situ boron neutron capture therapy for lung tumors at the RA-3 reactor in ArgentinaFarías, Rubén OscarGarabalino, Marcela AlejandraFerraris, SergioSanta María, JuanRovati, Osvaldo DanielLange, FernandoTrivillin, Verónica AndreaMonti Hughes, AndreaPozzi, Emiliano César CayetanoThorp, Silvia InésCurotto, PaulaBoltolussi, S.Altieri, S.Portu, Agustina MarianaSaint Martin, María Laura GiselaSchwint, Amanda ElenaGonzález, Sara JosefinaBnctEx Situ IrradiationLung TumorsBpa-FPharmacokineticshttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Purpose: Many types of lung tumors have a very poor prognosis due to their spread in the whole organ volume. The fact that boron neutron capture therapy (BNCT) would allow for selective targeting of all the nodules regardless of their position, prompted a preclinical feasibility study of ex situ BNCT at the thermal neutron facility of RA‐3 reactor in the province of Buenos Aires, Argentina. (l)‐4p‐dihydroxy‐borylphenylalanine fructose complex (BPA‐F) biodistribution studies in an adult sheep model and computational dosimetry for a human explanted lung were performed to evaluate the feasibility and the therapeutic potential of ex situ BNCT. Methods: Two kinds of boron biodistribution studies were carried out in the healthy sheep: a set of pharmacokinetic studies without lung excision, and a set that consisted of evaluation of boron concentration in the explanted and perfused lung. In order to assess the feasibility of the clinical application of ex situ BNCT at RA‐3, a case of multiple lung metastases was analyzed. A detailed computational representation of the geometry of the lung was built based on a real collapsed human lung. Dosimetric calculations and dose limiting considerations were based on the experimental results from the adult sheep, and on the most suitable information published in the literature. In addition, a workable treatment plan was considered to assess the clinical application in a realistic scenario. Results: Concentration‐time profiles for the normal sheep showed that the boron kinetics in blood, lung, and skin would adequately represent the boron behavior and absolute uptake expected in human tissues. Results strongly suggest that the distribution of the boron compound is spatially homogeneous in the lung. A constant lung‐to‐blood ratio of 1.3 ± 0.1 was observed from 80 min after the end of BPA‐F infusion. The fact that this ratio remains constant during time would allow the blood boron concentration to be used as a surrogate and indirect quantification of the estimated value in the explanted healthy lung. The proposed preclinical animal model allowed for the study of the explanted lung. As expected, the boron concentration values fell as a result of the application of the preservation protocol required to preserve the lung function. The distribution of the boron concentration retention factor was obtained for healthy lung, with a mean value of 0.46 ± 0.14 consistent with that reported for metastatic colon carcinoma model in rat perfused lung. Considering the human lung model and suitable tumor control probability for lung cancer, a promising average fraction of controlled lesions higher than 85% was obtained even for a low tumor‐to‐normal boron concentration ratio of 2. Conclusions: This work reports for the first time data supporting the validity of the ovine model as an adequate human surrogate in terms of boron kinetics and uptake in clinically relevant tissues. Collectively, the results and analysis presented would strongly suggest that ex situ whole lung BNCT irradiation is a feasible and highly promising technique that could greatly contribute to the treatment of metastatic lung disease in those patients without extrapulmonary spread, increasing not only the expected overall survival but also the resulting quality of life.Fil: Farías, Rubén Oscar. Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Gerencia de Radiobiología (Centro Atómico Constituyentes); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Garabalino, Marcela Alejandra. Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Gerencia de Radiobiología (Centro Atómico Constituyentes); ArgentinaFil: Ferraris, Sergio. Universidad Maimónides; ArgentinaFil: Santa María, Juan. Universidad Maimónides; ArgentinaFil: Rovati, Osvaldo Daniel. Universidad Maimónides; ArgentinaFil: Lange, Fernando. Universidad Maimónides; ArgentinaFil: Trivillin, Verónica Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Gerencia de Radiobiología (Centro Atómico Constituyentes); ArgentinaFil: Monti Hughes, Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Gerencia de Radiobiología (Centro Atómico Constituyentes); ArgentinaFil: Pozzi, Emiliano César Cayetano. Comisión Nacional de Energía Atómica; ArgentinaFil: Thorp, Silvia Inés. Comisión Nacional de Energía Atómica; ArgentinaFil: Curotto, Paula. Comisión Nacional de Energía Atómica; ArgentinaFil: Boltolussi, S. Istituto Nazionale Di Fisica Nucleare; ItaliaFil: Altieri, S.. Istituto Nazionale Di Fisica Nucleare; Italia. Università Di Pavia; ItaliaFil: Portu, Agustina Mariana. Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Gerencia de Radiobiología (Centro Atómico Constituyentes); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Saint Martin, María Laura Gisela. Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Gerencia de Radiobiología (Centro Atómico Constituyentes); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Schwint, Amanda Elena. Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Gerencia de Radiobiología (Centro Atómico Constituyentes); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: González, Sara Josefina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; ArgentinaWiley2015-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/41775Farías, Rubén Oscar; Garabalino, Marcela Alejandra; Ferraris, Sergio; Santa María, Juan; Rovati, Osvaldo Daniel; et al.; Toward a clinical application of ex situ boron neutron capture therapy for lung tumors at the RA-3 reactor in Argentina; Wiley; Medical Physics; 42; 7; 7-2015; 4161-41730094-2405CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1118/1.4922158info:eu-repo/semantics/altIdentifier/url/https://aapm.onlinelibrary.wiley.com/doi/abs/10.1118/1.4922158info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:37:51Zoai:ri.conicet.gov.ar:11336/41775instacron: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 09:37:51.767CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
| dc.title.none.fl_str_mv |
Toward a clinical application of ex situ boron neutron capture therapy for lung tumors at the RA-3 reactor in Argentina |
| title |
Toward a clinical application of ex situ boron neutron capture therapy for lung tumors at the RA-3 reactor in Argentina |
| spellingShingle |
Toward a clinical application of ex situ boron neutron capture therapy for lung tumors at the RA-3 reactor in Argentina Farías, Rubén Oscar Bnct Ex Situ Irradiation Lung Tumors Bpa-F Pharmacokinetics |
| title_short |
Toward a clinical application of ex situ boron neutron capture therapy for lung tumors at the RA-3 reactor in Argentina |
| title_full |
Toward a clinical application of ex situ boron neutron capture therapy for lung tumors at the RA-3 reactor in Argentina |
| title_fullStr |
Toward a clinical application of ex situ boron neutron capture therapy for lung tumors at the RA-3 reactor in Argentina |
| title_full_unstemmed |
Toward a clinical application of ex situ boron neutron capture therapy for lung tumors at the RA-3 reactor in Argentina |
| title_sort |
Toward a clinical application of ex situ boron neutron capture therapy for lung tumors at the RA-3 reactor in Argentina |
| dc.creator.none.fl_str_mv |
Farías, Rubén Oscar Garabalino, Marcela Alejandra Ferraris, Sergio Santa María, Juan Rovati, Osvaldo Daniel Lange, Fernando Trivillin, Verónica Andrea Monti Hughes, Andrea Pozzi, Emiliano César Cayetano Thorp, Silvia Inés Curotto, Paula Boltolussi, S. Altieri, S. Portu, Agustina Mariana Saint Martin, María Laura Gisela Schwint, Amanda Elena González, Sara Josefina |
| author |
Farías, Rubén Oscar |
| author_facet |
Farías, Rubén Oscar Garabalino, Marcela Alejandra Ferraris, Sergio Santa María, Juan Rovati, Osvaldo Daniel Lange, Fernando Trivillin, Verónica Andrea Monti Hughes, Andrea Pozzi, Emiliano César Cayetano Thorp, Silvia Inés Curotto, Paula Boltolussi, S. Altieri, S. Portu, Agustina Mariana Saint Martin, María Laura Gisela Schwint, Amanda Elena González, Sara Josefina |
| author_role |
author |
| author2 |
Garabalino, Marcela Alejandra Ferraris, Sergio Santa María, Juan Rovati, Osvaldo Daniel Lange, Fernando Trivillin, Verónica Andrea Monti Hughes, Andrea Pozzi, Emiliano César Cayetano Thorp, Silvia Inés Curotto, Paula Boltolussi, S. Altieri, S. Portu, Agustina Mariana Saint Martin, María Laura Gisela Schwint, Amanda Elena González, Sara Josefina |
| author2_role |
author author author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
Bnct Ex Situ Irradiation Lung Tumors Bpa-F Pharmacokinetics |
| topic |
Bnct Ex Situ Irradiation Lung Tumors Bpa-F Pharmacokinetics |
| purl_subject.fl_str_mv |
https://purl.org/becyt/ford/3.1 https://purl.org/becyt/ford/3 |
| dc.description.none.fl_txt_mv |
Purpose: Many types of lung tumors have a very poor prognosis due to their spread in the whole organ volume. The fact that boron neutron capture therapy (BNCT) would allow for selective targeting of all the nodules regardless of their position, prompted a preclinical feasibility study of ex situ BNCT at the thermal neutron facility of RA‐3 reactor in the province of Buenos Aires, Argentina. (l)‐4p‐dihydroxy‐borylphenylalanine fructose complex (BPA‐F) biodistribution studies in an adult sheep model and computational dosimetry for a human explanted lung were performed to evaluate the feasibility and the therapeutic potential of ex situ BNCT. Methods: Two kinds of boron biodistribution studies were carried out in the healthy sheep: a set of pharmacokinetic studies without lung excision, and a set that consisted of evaluation of boron concentration in the explanted and perfused lung. In order to assess the feasibility of the clinical application of ex situ BNCT at RA‐3, a case of multiple lung metastases was analyzed. A detailed computational representation of the geometry of the lung was built based on a real collapsed human lung. Dosimetric calculations and dose limiting considerations were based on the experimental results from the adult sheep, and on the most suitable information published in the literature. In addition, a workable treatment plan was considered to assess the clinical application in a realistic scenario. Results: Concentration‐time profiles for the normal sheep showed that the boron kinetics in blood, lung, and skin would adequately represent the boron behavior and absolute uptake expected in human tissues. Results strongly suggest that the distribution of the boron compound is spatially homogeneous in the lung. A constant lung‐to‐blood ratio of 1.3 ± 0.1 was observed from 80 min after the end of BPA‐F infusion. The fact that this ratio remains constant during time would allow the blood boron concentration to be used as a surrogate and indirect quantification of the estimated value in the explanted healthy lung. The proposed preclinical animal model allowed for the study of the explanted lung. As expected, the boron concentration values fell as a result of the application of the preservation protocol required to preserve the lung function. The distribution of the boron concentration retention factor was obtained for healthy lung, with a mean value of 0.46 ± 0.14 consistent with that reported for metastatic colon carcinoma model in rat perfused lung. Considering the human lung model and suitable tumor control probability for lung cancer, a promising average fraction of controlled lesions higher than 85% was obtained even for a low tumor‐to‐normal boron concentration ratio of 2. Conclusions: This work reports for the first time data supporting the validity of the ovine model as an adequate human surrogate in terms of boron kinetics and uptake in clinically relevant tissues. Collectively, the results and analysis presented would strongly suggest that ex situ whole lung BNCT irradiation is a feasible and highly promising technique that could greatly contribute to the treatment of metastatic lung disease in those patients without extrapulmonary spread, increasing not only the expected overall survival but also the resulting quality of life. Fil: Farías, Rubén Oscar. Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Gerencia de Radiobiología (Centro Atómico Constituyentes); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Garabalino, Marcela Alejandra. Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Gerencia de Radiobiología (Centro Atómico Constituyentes); Argentina Fil: Ferraris, Sergio. Universidad Maimónides; Argentina Fil: Santa María, Juan. Universidad Maimónides; Argentina Fil: Rovati, Osvaldo Daniel. Universidad Maimónides; Argentina Fil: Lange, Fernando. Universidad Maimónides; Argentina Fil: Trivillin, Verónica Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Gerencia de Radiobiología (Centro Atómico Constituyentes); Argentina Fil: Monti Hughes, Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Gerencia de Radiobiología (Centro Atómico Constituyentes); Argentina Fil: Pozzi, Emiliano César Cayetano. Comisión Nacional de Energía Atómica; Argentina Fil: Thorp, Silvia Inés. Comisión Nacional de Energía Atómica; Argentina Fil: Curotto, Paula. Comisión Nacional de Energía Atómica; Argentina Fil: Boltolussi, S. Istituto Nazionale Di Fisica Nucleare; Italia Fil: Altieri, S.. Istituto Nazionale Di Fisica Nucleare; Italia. Università Di Pavia; Italia Fil: Portu, Agustina Mariana. Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Gerencia de Radiobiología (Centro Atómico Constituyentes); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Saint Martin, María Laura Gisela. Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Gerencia de Radiobiología (Centro Atómico Constituyentes); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Schwint, Amanda Elena. Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Gerencia de Radiobiología (Centro Atómico Constituyentes); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: González, Sara Josefina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; Argentina |
| description |
Purpose: Many types of lung tumors have a very poor prognosis due to their spread in the whole organ volume. The fact that boron neutron capture therapy (BNCT) would allow for selective targeting of all the nodules regardless of their position, prompted a preclinical feasibility study of ex situ BNCT at the thermal neutron facility of RA‐3 reactor in the province of Buenos Aires, Argentina. (l)‐4p‐dihydroxy‐borylphenylalanine fructose complex (BPA‐F) biodistribution studies in an adult sheep model and computational dosimetry for a human explanted lung were performed to evaluate the feasibility and the therapeutic potential of ex situ BNCT. Methods: Two kinds of boron biodistribution studies were carried out in the healthy sheep: a set of pharmacokinetic studies without lung excision, and a set that consisted of evaluation of boron concentration in the explanted and perfused lung. In order to assess the feasibility of the clinical application of ex situ BNCT at RA‐3, a case of multiple lung metastases was analyzed. A detailed computational representation of the geometry of the lung was built based on a real collapsed human lung. Dosimetric calculations and dose limiting considerations were based on the experimental results from the adult sheep, and on the most suitable information published in the literature. In addition, a workable treatment plan was considered to assess the clinical application in a realistic scenario. Results: Concentration‐time profiles for the normal sheep showed that the boron kinetics in blood, lung, and skin would adequately represent the boron behavior and absolute uptake expected in human tissues. Results strongly suggest that the distribution of the boron compound is spatially homogeneous in the lung. A constant lung‐to‐blood ratio of 1.3 ± 0.1 was observed from 80 min after the end of BPA‐F infusion. The fact that this ratio remains constant during time would allow the blood boron concentration to be used as a surrogate and indirect quantification of the estimated value in the explanted healthy lung. The proposed preclinical animal model allowed for the study of the explanted lung. As expected, the boron concentration values fell as a result of the application of the preservation protocol required to preserve the lung function. The distribution of the boron concentration retention factor was obtained for healthy lung, with a mean value of 0.46 ± 0.14 consistent with that reported for metastatic colon carcinoma model in rat perfused lung. Considering the human lung model and suitable tumor control probability for lung cancer, a promising average fraction of controlled lesions higher than 85% was obtained even for a low tumor‐to‐normal boron concentration ratio of 2. Conclusions: This work reports for the first time data supporting the validity of the ovine model as an adequate human surrogate in terms of boron kinetics and uptake in clinically relevant tissues. Collectively, the results and analysis presented would strongly suggest that ex situ whole lung BNCT irradiation is a feasible and highly promising technique that could greatly contribute to the treatment of metastatic lung disease in those patients without extrapulmonary spread, increasing not only the expected overall survival but also the resulting quality of life. |
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2015 |
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2015-07 |
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http://hdl.handle.net/11336/41775 Farías, Rubén Oscar; Garabalino, Marcela Alejandra; Ferraris, Sergio; Santa María, Juan; Rovati, Osvaldo Daniel; et al.; Toward a clinical application of ex situ boron neutron capture therapy for lung tumors at the RA-3 reactor in Argentina; Wiley; Medical Physics; 42; 7; 7-2015; 4161-4173 0094-2405 CONICET Digital CONICET |
| url |
http://hdl.handle.net/11336/41775 |
| identifier_str_mv |
Farías, Rubén Oscar; Garabalino, Marcela Alejandra; Ferraris, Sergio; Santa María, Juan; Rovati, Osvaldo Daniel; et al.; Toward a clinical application of ex situ boron neutron capture therapy for lung tumors at the RA-3 reactor in Argentina; Wiley; Medical Physics; 42; 7; 7-2015; 4161-4173 0094-2405 CONICET Digital CONICET |
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eng |
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eng |
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CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
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dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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