scholarly journals Implications of radiation microdosimetry for accelerator-based boron neutron capture therapy: a radiobiological perspective

2020 ◽  
Vol 93 (1111) ◽  
pp. 20200311
Author(s):  
Hisanori Fukunaga ◽  
Yusuke Matsuya ◽  
Koichi Tokuuye ◽  
Motoko Omura

Boron neutron capture therapy (BNCT) has great potential to selectively destroy cancer cells while sparing surrounding normal cells. The basic concept of BNCT was developed in the 1930s, but it has not yet been commonly used in clinical practice, even though there is now a large number of experimental and translational studies demonstrating its marked therapeutic potential. With the development of neutron accelerators that can be installed in medical institutions, accelerator-based BNCT is expected to become available at several medical institutes around the world in the near future. In this commentary, from the point of view of radiation microdosimetry, we discuss the biological effects of BNCT, especially the underlying mechanisms of compound biological effectiveness. Radiobiological perspectives provide insight into the effectiveness of BNCT in creating a synergy effect in the field of clinical oncology.

Author(s):  
María Pedrosa-Rivera ◽  
Javier Praena ◽  
Ignacio Porras ◽  
Manuel Pedro Sabariego ◽  
Ulli Köster ◽  
...  

The experimental determination of the relative biological effectiveness of thermal neutron factors is fundamental in Boron Neutron Capture Therapy. Present values have been obtained using mixed beams consisting of both neutrons and photons of various energies. A common weighting factor has been used for both thermal and fast neutron doses, although such an approach has been questioned. At the nuclear reactor of the Institut Laue-Langevin a pure low-energy neutron beam has been used to determine thermal neutron relative biological effectiveness factors. Different tumor cell lines, corresponding to glioblastoma, melanoma, and head and neck squamous cell carcinoma, and non-tumor cell lines (lung fibroblast and embryonic kidney) have been irradiated using an experimental arrangement designed to minimise neutron-induced secondary gamma radiation. Additionally, the cells were irradiated with photons at a medical linear accelerator, providing reference data for comparison with that from neutron irradiation. Survival and proliferation were studied after irradiation, yielding the Relative Biological Effectiveness corresponding to the damage of thermal neutrons for the different tissue types.


2018 ◽  
Vol 35 (3) ◽  
pp. 203-207
Author(s):  
Ren-Tai Chiang

 The direct and indirect ionizing radiation sources for boron neutron capture therapy (BNCT)are identi?ed. The mechanisms of physical, chemical and biological radiation interactions for BNCT are systematically described and analyzed. The relationship between the effect of biological radiation and radiation dose are illustrated and analyzed for BNCT. If the DNAs in chromosomes are damaged by ion- izing radiations, the instructions that control the cell function and reproduction are also damaged. This radiation damage may be reparable, irreparable, or incorrectly repaired. The irreparable damage can result in cell death at next mitosis while incorrectly repaired damage can result in mutation. Cell death leads to variable degrees of tissue dysfunction, which can affect the whole organism’s functions. Can- cer cells cannot live without oxygen and nutrients via the blood supply. A cancer tumor can be shrunk by damaging angiogenic factors and/or capillaries via ionizing radiations to decrease blood supply into the cancer tumor. The collisions between ionizing radiations and the target nuclei and the absorption of the ultraviolet, visible light, infrared and microwaves from bremsstrahlung in the tumor can heat up and damage cancer cells and function as thermotherapy. The cancer cells are more chemically and biologically sensitive at the BNCT-induced higher temperatures since free-radical-induced chemical re- actions are more random and vigorous at higher temperatures after irradiation, and consequently the cancer cells are harder to divide or even survive due to more cell DNA damage. BNCT is demonstrated via a recent clinical trial that it is quite effective in treating recurrent nasopharyngeal cancer.


Cells ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 2302
Author(s):  
Seth W. Streitmatter ◽  
Robert D. Stewart ◽  
Gregory Moffitt ◽  
Tatjana Jevremovic

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.


2017 ◽  
Vol 2 (1) ◽  
pp. 9
Author(s):  
Isman Mulyadi Triatmoko ◽  
Sutjipto Sutjipto

A study of the assessment criteria covers the synthesis and characterization of agent and test their biological effectiveness as boron neutron capture therapy (BNCT) agents in cancer treatment. The cellular uptake of this agent into the glioblastoma cells was assessed by boron analysis (ICP-MS) and by fluorescence imaging (confocal microscopy). The agent enters the glioblastoma cells exhibiting a similar profile, i.e., preferential accumulation in the cytoskeleton and membranes and a low cytotoxic activity (IC<sub>50</sub> values higher than 200 μM). The cytotoxic activity and cellular morphological alterations after neutron irradiation in the Research Reactor (&gt;10<sup>7</sup> neutrons cm<sup>−2</sup> s<sup>−1</sup>) were assessed by the MTT assay and by electron microscopy (TEM). Post neutron irradiation revealed that BNCT has a higher cytotoxic effect on the glioblastoma cells. Results provide a strong rationale for considering one of these compounds as a lead candidate for a new BNCT agent.


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