skip to main content
Show search Show menu
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Toward a clinical application of ex situ boron neutron capture therapy for lung tumors at the RA-3 reactor in Argentina

Abstract

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 suitablemore » 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.« less

Authors:
; ; ; ; ; ; ; ; ; ; ;  [1]; ; ; ;  [2];  [3];  [4]
+ Show Author Affiliations
  1. Comisión Nacional de Energía Atómica (CNEA), San Martín 1650 (Argentina)
  2. CIDME, Universidad Maimónides, Buenos Aires 1405 (Argentina)
  3. Istituto Nazionale di Fisica Nucleare, Sezione di Pavia 27100 (Italy)
  4. Istituto Nazionale di Fisica Nucleare, Sezione di Pavia 27100, Italy and Dipartimento di Fisica, Università di Pavia, Pavia 27100 (Italy)
Publication Date:
OSTI Identifier:
22413627
Resource Type:
Journal Article
Journal Name:
Medical Physics
Additional Journal Information:
Journal Volume: 42; Journal Issue: 7; Other Information: (c) 2015 American Association of Physicists in Medicine; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0094-2405
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; BORON; BORON COMPOUNDS; CARCINOMAS; FEASIBILITY STUDIES; LARGE INTESTINE; LUNGS; NEUTRON CAPTURE THERAPY; RA-3 REACTOR; RATS; SHEEP

Citation Formats

Farías, R. O., Trivillin, V. A., Portu, A. M., Schwint, A. E., González, S. J., E-mail: srgonzal@cnea.gov.ar, Garabalino, M. A., Monti Hughes, A., Pozzi, E. C. C., Thorp, S. I., Curotto, P., Miller, M. E., Santa Cruz, G. A., Saint Martin, G., Ferraris, S., Santa María, J., Rovati, O., Lange, F., Bortolussi, S., and Altieri, S. Toward a clinical application of ex situ boron neutron capture therapy for lung tumors at the RA-3 reactor in Argentina. United States: N. p., 2015. Web. doi:10.1118/1.4922158.
Copy to clipboard
Farías, R. O., Trivillin, V. A., Portu, A. M., Schwint, A. E., González, S. J., E-mail: srgonzal@cnea.gov.ar, Garabalino, M. A., Monti Hughes, A., Pozzi, E. C. C., Thorp, S. I., Curotto, P., Miller, M. E., Santa Cruz, G. A., Saint Martin, G., Ferraris, S., Santa María, J., Rovati, O., Lange, F., Bortolussi, S., & Altieri, S. Toward a clinical application of ex situ boron neutron capture therapy for lung tumors at the RA-3 reactor in Argentina. United States. https://doi.org/10.1118/1.4922158
Copy to clipboard
Farías, R. O., Trivillin, V. A., Portu, A. M., Schwint, A. E., González, S. J., E-mail: srgonzal@cnea.gov.ar, Garabalino, M. A., Monti Hughes, A., Pozzi, E. C. C., Thorp, S. I., Curotto, P., Miller, M. E., Santa Cruz, G. A., Saint Martin, G., Ferraris, S., Santa María, J., Rovati, O., Lange, F., Bortolussi, S., and Altieri, S. 2015. "Toward a clinical application of ex situ boron neutron capture therapy for lung tumors at the RA-3 reactor in Argentina". United States. https://doi.org/10.1118/1.4922158.
Copy to clipboard
@article{osti_22413627,
title = {Toward a clinical application of ex situ boron neutron capture therapy for lung tumors at the RA-3 reactor in Argentina},
author = {Farías, R. O. and Trivillin, V. A. and Portu, A. M. and Schwint, A. E. and González, S. J., E-mail: srgonzal@cnea.gov.ar and Garabalino, M. A. and Monti Hughes, A. and Pozzi, E. C. C. and Thorp, S. I. and Curotto, P. and Miller, M. E. and Santa Cruz, G. A. and Saint Martin, G. and Ferraris, S. and Santa María, J. and Rovati, O. and Lange, F. and Bortolussi, S. and Altieri, S.},
abstractNote = {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.},
doi = {10.1118/1.4922158},
url = {https://www.osti.gov/biblio/22413627}, journal = {Medical Physics},
issn = {0094-2405},
number = 7,
volume = 42,
place = {United States},
year = {Wed Jul 15 00:00:00 EDT 2015},
month = {Wed Jul 15 00:00:00 EDT 2015}
}
Copy to clipboard
Journal Article:
https://doi.org/10.1118/1.4922158
Other availability
Find in Google Scholar Find in Google Scholar
Search WorldCat Search WorldCat to find libraries that may hold this journal
Save / Share:
Export Metadata
Save to My Library
You must Sign In or Create an Account in order to save documents to your library.

Similar records in OSTI.GOV collections: