Microdosimetric Modeling of CBE for BNCT Considering Subcellular B-10 Heterogeneity
Abstract
Purpose
In boron neutron capture therapy (BNCT), heterogeneous subcellular distributions of 10B critically affect neutron energy deposition and cell-killing effectiveness. However, biophysical models explicitly incorporating subcellular 10B heterogeneity in compound biological effectiveness (CBE) calculations remain scarce. Here, we introduce a microdosimetry-based CBE model integrating subcellular 10B distribution to improve radiobiological effectiveness estimation.
Methods
A 3×3×3 cellular voxel matrix was constructed, and Monte Carlo simulations were conducted with 10B distributed in concentric shells from the nuclear boundary to the cell membrane, alongside a uniform extracellular distribution. Microdosimetric spectra within the subnuclear domain were computed, along with effective particle fluence coefficients for α and ⁷Li ions produced by thermal neutron capture in 10B. Based on these quantities, we developed a Composite Microdosimetric Kinetic Model (C-MKM) to calculate the CBE for arbitrary 10B distributions. The model was applied to BPA and BSH delivery scenarios and validated against published experimental and simulation data.
Results
A database of microdosimetric spectra and effective particle fluence coefficients was established, corresponding to various subcellular 10B shell distributions. The dose-mean lineal energy y ranged from 181.6 to 216.6 keV/μm, while effective particle fluence coefficients for α and ⁷Li ions ranged from 8.71×10-3 to 2.85×10-2. For HSG cells at a 10% survival fraction, the C-MKM yielded CBE values of 2.58 for BPA and 1.27 for BSH, in good agreement with published data.
Conclusion
By explicitly incorporating subcellular 10B heterogeneity, the proposed C-MKM enables more accurate CBE estimation in BNCT, providing a robust framework for photon-equivalent dose evaluation and facilitating enhanced treatment planning.