Spread-out Bragg peak Monte Carlo simulation of proton therapy with 15N-targeted <i>in situ</i> generation of 12C ions and α-particles

Proton therapy has been criticized due to its relatively low biological effectiveness compared with heavy particle therapy, for example, 12C ion therapy. Recently, we proposed a new strategy for proton therapy to improve biological effectiveness, termed as nitrogen-targeting-Proton-Carbon-Alpha-Therapy (Proton-CAT). The previous work has demonstrated its feasibility to enhance the yield of high-linear energy transfer (LET) particles with a monoenergetic proton beam. To assess the feasibility of Proton-CAT for spread-out Bragg peak (SOBP) beams, we employed Monte Carlo simulations at both macroscopic and microscopic levels. For macroscopic calculations, an SOBP of 24–32 MeV protons with a modulation width of 3.0 mm was constructed and irradiated into a tissue-equivalent phantom with and without 15N material (10% and 30% 15N concentration). Dose deposition by protons, alpha particles, and 12C ions was scored along the beam path. For microscopic evaluation, a cell model was used to assess the damage inflicted by energetic particles (12C ions and α-particles). The results demonstrated the advantages of the Proton-CAT. Within the SOBP (0.6–0.82 cm depth), the average dose amplification for 12C ions exceeded 15.8% (10% 15N) and 38.5% (30% 15N), while for α-particles, it surpassed 68.5% (10% 15N) and 203.8% (30% 15N). Moreover, the energy deposition of 12C ions and α-particles in cell nucleus reached up to 3.50 keV μm−3 (10% and 30% 15N concentration). These findings support the hypothesis that the Proton-CAT has the feasibility to yield short-range, high-LET 12C ions and α-particles within the SOBP region.