Radiobiological impact of gadolinium neutron capture from proton therapy and alternative neutron sources using TOPAS-nBio

Purpose: A multi-scale investigation of the biological properties of gadolinium neutron capture (GdNC) therapy with applications in particle therapy is conducted using the TOPAS Monte Carlo (MC) simulation code. The simulation results are used to quantify the amount of gadolinium dose enhancement produced as a result of the secondary neutron production from proton therapy scaled by measured data. Materials and methods: MC modeling was performed using the radiobiology extension TOol for PArticle Simulation TOPAS-nBio MC simulation code to study the radiobiological effects produced from GdNC on a segment of DNA, a spherical cellular model, and from the modeling of previous experimental measurements. The average RBE values were calculated from two methods, microdosimetric kinematic (MK) and biological weighting r(y) within a 2 nm DNA segment for GdNC. The single-strand breaks (SSBs) and double-strand breaks (DSBs) were calculated from within the nucleus of a 20 µm diameter, spherical cell model. From a previous experimental proton therapy measurement using a spread-out Bragg peak (SOBP) of 4.5–9.5 cm and a delivered absorbed dose of 10.4 Gy, the amount of Gd neutron captures was calculated and used to quantify the amount of GdNC absolute dose from particle therapy. Results: The average RBE from microdosimetric kinematic and biological weighting was 1.35, and 1.70 for a 10% cell survival on HSG cell-line and weighting function data from early intestinal tolerance of mice. From a central isotropic GdNC source, the energy deposition is found to decrease from roughly 2.7 eV per capture down to approximately 0.01 eV per capture, a drop of two orders of magnitude within 50 nm. This result suggests that Gd needs to be close to the DNA (within 10–20 nm) in order for neutron capture to induce a significant dose enhancement due to the short-range electrons emitted after Gd neutron capture. Within a spherical cell model, the SSBs, and DSBs were determined to be 39 and 1.5 per neutron capture, respectively. From the total neutron captures produced from an experimental proton therapy measurement on a 3000 PPM Gd solution, an insignificant absolute Gd dose enhancement was quantified to be 5.4 × 10⁻⁶ Gy per Gy of administered proton dose. Conclusion: From this study and literature review, the production of secondary thermal neutrons from proton therapy is determined to be a limiting factor and unlikely to produce a clinically useful dose enhancement for secondary neutron capture therapy. Moreover, alternative neutron sources, such as, a compact deuterium-tritium (D-T) neutron generator, a “high yield” deuterium-deuterium (D-D) generator, or an industrial strength (100 mg) ²⁵²Cf source were investigated, with the ²⁵²Cf source the most likely to be capable of producing enough neutrons for 1 Gy of localized GdNC absolute dose within a reasonable treatment time.