Mechanistic Modeling of the Relative Biological Effectiveness of Boron Neutron Capture Therapy

Accurate dosimetry and determination of the biological effectiveness of boron neutron capture therapy (BNCT) is challenging because of the mix of different types and energies of radiation at the cellular and subcellular levels. In this paper, we present a computational, multiscale system of models t...

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Main Authors: Seth W. Streitmatter, Robert D. Stewart, Gregory Moffitt, Tatjana Jevremovic
Format: Article
Language:English
Published: MDPI AG 2020-10-01
Series:Cells
Subjects:
RBE
CBE
RMF
Online Access:https://www.mdpi.com/2073-4409/9/10/2302
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spelling doaj-c5f3fd4e442e49228f54600b35b4ffe52020-11-25T03:59:41ZengMDPI AGCells2073-44092020-10-0192302230210.3390/cells9102302Mechanistic Modeling of the Relative Biological Effectiveness of Boron Neutron Capture TherapySeth W. Streitmatter0Robert D. Stewart1Gregory Moffitt2Tatjana Jevremovic3Medical Imaging Physics and Radiation Safety, Department of Radiology and Imaging Sciences, University of Utah Health, Salt Lake City, UT 84132, USADepartment of Radiation Oncology, University of Washington, Seattle, WA 98115, USADepartment of Radiation Oncology, University of Washington, Seattle, WA 98115, USAInternational Atomic Energy Agency (IAEA), 1020 Wien, AustriaAccurate dosimetry and determination of the biological effectiveness of boron neutron capture therapy (BNCT) is challenging because of the mix of different types and energies of radiation at the cellular and subcellular levels. In this paper, we present a computational, multiscale system of models to better assess the relative biological effectiveness (RBE) and compound biological effectiveness (CBE) of several neutron sources as applied to BNCT using boronophenylalanine (BPA) and a potential monoclonal antibody (mAb) that targets HER-2-positive cells with Trastuzumab. The multiscale model is tested against published in vitro and in vivo measurements of cell survival with and without boron. The combined dosimetric and radiobiological model includes an analytical formulation that accounts for the type of neutron source, the tissue- or cancer-specific dose–response characteristics, and the microdistribution of boron. Tests of the model against results from published experiments with and without boron show good agreement between modeled and experimentally determined cell survival for neutrons alone and in combination with boron. The system of models developed in this work is potentially useful as an aid for the optimization and individualization of BNCT for HER-2-positive cancers, as well as other cancers, that can be targeted with mAb or a conventional BPA compound.https://www.mdpi.com/2073-4409/9/10/2302RBEBNCTCBEMCDSRMFMCNP
collection DOAJ
language English
format Article
sources DOAJ
author Seth W. Streitmatter
Robert D. Stewart
Gregory Moffitt
Tatjana Jevremovic
spellingShingle Seth W. Streitmatter
Robert D. Stewart
Gregory Moffitt
Tatjana Jevremovic
Mechanistic Modeling of the Relative Biological Effectiveness of Boron Neutron Capture Therapy
Cells
RBE
BNCT
CBE
MCDS
RMF
MCNP
author_facet Seth W. Streitmatter
Robert D. Stewart
Gregory Moffitt
Tatjana Jevremovic
author_sort Seth W. Streitmatter
title Mechanistic Modeling of the Relative Biological Effectiveness of Boron Neutron Capture Therapy
title_short Mechanistic Modeling of the Relative Biological Effectiveness of Boron Neutron Capture Therapy
title_full Mechanistic Modeling of the Relative Biological Effectiveness of Boron Neutron Capture Therapy
title_fullStr Mechanistic Modeling of the Relative Biological Effectiveness of Boron Neutron Capture Therapy
title_full_unstemmed Mechanistic Modeling of the Relative Biological Effectiveness of Boron Neutron Capture Therapy
title_sort mechanistic modeling of the relative biological effectiveness of boron neutron capture therapy
publisher MDPI AG
series Cells
issn 2073-4409
publishDate 2020-10-01
description Accurate dosimetry and determination of the biological effectiveness of boron neutron capture therapy (BNCT) is challenging because of the mix of different types and energies of radiation at the cellular and subcellular levels. In this paper, we present a computational, multiscale system of models to better assess the relative biological effectiveness (RBE) and compound biological effectiveness (CBE) of several neutron sources as applied to BNCT using boronophenylalanine (BPA) and a potential monoclonal antibody (mAb) that targets HER-2-positive cells with Trastuzumab. The multiscale model is tested against published in vitro and in vivo measurements of cell survival with and without boron. The combined dosimetric and radiobiological model includes an analytical formulation that accounts for the type of neutron source, the tissue- or cancer-specific dose–response characteristics, and the microdistribution of boron. Tests of the model against results from published experiments with and without boron show good agreement between modeled and experimentally determined cell survival for neutrons alone and in combination with boron. The system of models developed in this work is potentially useful as an aid for the optimization and individualization of BNCT for HER-2-positive cancers, as well as other cancers, that can be targeted with mAb or a conventional BPA compound.
topic RBE
BNCT
CBE
MCDS
RMF
MCNP
url https://www.mdpi.com/2073-4409/9/10/2302
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