A Model for Estimating Dose-Rate Effects on Cell-Killing of Human Melanoma after Boron Neutron Capture Therapy.

Motoko Omura,Hisanori Fukunaga,Hiroyuki Date,Yusuke Matsuya

doi:10.3390/cells9051117

Abstract

Boron neutron capture therapy (BNCT) is a type of radiation therapy for eradicating tumor cells through a 10B(n,α)7Li reaction in the presence of 10B in cancer cells. When delivering a high absorbed dose to cancer cells using BNCT, both the timeline of 10B concentrations and the relative long dose-delivery time compared to photon therapy must be considered. Changes in radiosensitivity during such a long dose-delivery time can reduce the probability of tumor control; however, such changes have not yet been evaluated. Here, we propose an improved integrated microdosimetric-kinetic model that accounts for changes in microdosimetric quantities and dose rates depending on the 10B concentration and investigate the cell recovery (dose-rate effects) of melanoma during BNCT irradiation. The integrated microdosimetric–kinetic model used in this study considers both sub-lethal damage repair and changes in microdosimetric quantities during irradiation. The model, coupled with the Monte Carlo track structure simulation code of the Particle and Heavy Ion Transport code System, shows good agreement with in vitro experimental data for acute exposure to 60Co γ-rays, thermal neutrons, and BNCT with 10B concentrations of 10 ppm. This indicates that microdosimetric quantities are important parameters for predicting dose-response curves for cell survival under BNCT irradiations. Furthermore, the model estimation at the endpoint of the mean activation dose exhibits a reduced impact of cell recovery during BNCT irradiations with high linear energy transfer (LET) compared to 60Co γ-rays irradiation with low LET. Throughout this study, we discuss the advantages of BNCT for enhancing the killing of cancer cells with a reduced dose-rate dependency. If the neutron spectrum and the timelines for drug and dose delivery are provided, the present model will make it possible to predict radiosensitivity for more realistic dose-delivery schemes in BNCT irradiations.

Highlights

Radiation therapy is one of the treatment approaches for eradicating tumors in clinical practice [1].Among several clinical modalities such as 6MV-linac X-ray, proton, carbon ion, and neutron capture therapies [2,3,4,5,6,7], boron neutron capture therapy (BNCT), in which 10 B is administered to tumor cells [8], is one of the most effective approaches for treating malignant tumors
It should be noted that we focused on both changes in microdosimetric quantity and cell regimens, one with a 40 minute dose-delivery time and the other with a 158 minute dose-delivery recovery resulting from SLDR, excluding the IDREs
The tumor-cell-selective killing kinetics are recognized as an important issue when discussing the

Summary

Introduction

Among several clinical modalities such as 6MV-linac X-ray, proton, carbon ion, and neutron capture therapies [2,3,4,5,6,7], boron neutron capture therapy (BNCT), in which 10 B is administered to tumor cells [8], is one of the most effective approaches for treating malignant tumors. Cells 2020, 9, 1117 potential for treating cancers such as melanoma, brain tumors, and head and neck cancers. It has not been routinely applied in clinical practice because, for a long time, availability was limited to facilities with nuclear reactors. BNCT for cancer treatment will become available at several medical institutes around the world that are equipped with accelerator-based BNCT modalities

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Conclusion