An experimentally calibrated nanodosimetry-based framework for predicting LET-dependent relative biological effectiveness in proton boron capture therapy.

OBJECTIVE

Proton boron capture therapy (PBCT) studies focus on physical dose enhancement or biological observations, while quantitative prediction of biological effectiveness remains limited. This study aimed to establish a framework combining Monte Carlo (MC) simulation, nanodosimetry, and radiobiological experiments to evaluate the relative biological effectiveness (RBE) of PBCT.

APPROACH: Geant4-based MC simulations and a pre-calculated nanodosimetric database were used to determine mixed-field nanodosimetric parameters, including M1, M2, and F2. Clonogenic survival experiments were performed using a clinical 70 MeV proton beam and a 6 MV photon beam. U-87 MG cells were irradiated with photons, protons, and PBCT at 0, 2, 4, 6, and 8 Gy using boronophenylalanine (BPA, 21.0 ppm 11B). Survival data were fitted with the linear-quadratic model, and the resulting α and β values were used to optimize the Logistic Nanodosimetry Model (LNDM) for depth-dependent RBE prediction.

MAIN

RESULTS

The LNDM, combined with MC-derived nanodosimetric parameters and experimental survival data, reproduced the measured radiobiological response with differences in α and β below 0.5% at the experimental cell position, corresponding to a water-equivalent depth (WED) of 3.9 cm and located on the rising edge of the Bragg peak. PBCT consistently exhibited higher α and RBE values than proton irradiation across the investigated LET range. At 3.9 cm, PBCT increased RBE by 8.7% compared with protons. For the 70 MeV beam, PBCT yielded α = 0.116 Gy⁻¹, β = 0.023 Gy⁻², and RBE = 1.25, compared with α = 0.076 Gy⁻¹, β = 0.023 Gy⁻², and RBE = 1.15 for proton therapy.

SIGNIFICANCE: An experimentally calibrated framework integrating MC simulation, nanodosimetry, radiobiological experiments, and the LNDM was established for LET-dependent PBCT RBE prediction based on biological calibration data. PBCT showed consistently higher RBE than proton therapy, with a greater advantage at higher LET, supporting future biological optimization of PBCT.