The low-LET radiation contribution to the tumor dose in diffusing alpha-emitters radiation therapy

Background: Diffusing alpha-emitters Radiation Therapy (“Alpha DaRT”) is a new technique that enables the use of alpha particles for the treatment of solid tumors. Alpha DaRT employs interstitial sources carrying a few (Formula presented.) Ci of (Formula presented.) Ra below their surface, designed to release a chain of short-lived atoms (progeny of (Formula presented.) Ra) which emit alpha particles, along with beta, Auger, and conversion electrons, x- and gamma rays. These atoms diffuse around the source and create—primarily through their alpha decays—a lethal high-dose region measuring a few millimeters in diameter. Purpose: While previous studies focused on the dose from the alpha emissions alone, this work addresses the electron and photon dose contributed by the diffusing atoms and by the atoms remaining on the source surface, for both a single Alpha DaRT source and multi-source lattices. This allows to evaluate the low-LET contribution to the tumor dose and tumor cell survival, and demonstrate the sparing of surrounding healthy tissue. Methods: The low-LET dose is calculated using the EGSnrc and FLUKA Monte Carlo (MC) codes. We compare the results of a simple line-source approximation with no diffusion to those of a full simulation, which implements a realistic source geometry and the spread of diffusing atoms. We consider two opposite scenarios: one with low diffusion and high (Formula presented.) Pb leakage, and the other with high diffusion and low leakage. The low-LET dose in source lattices is calculated by superposition of single-source contributions. Its effect on cell survival is estimated with the linear quadratic model in the limit of low dose rate. Results: For sources carrying 3 (Formula presented.) Ci/cm (Formula presented.) Ra arranged in a hexagonal lattice with 4 mm spacing, the minimal low-LET dose between sources is (Formula presented.) Gy for the two test cases and is dominated by the beta contribution. The low-LET dose drops below 5 Gy (Formula presented.) mm away from the outermost source in the lattice with an effective maximal dose rate of (Formula presented.) Gy/h. The accuracy of the line-source/no-diffusion approximation is (Formula presented.) for the total low-LET dose over clinically relevant distances (2–4 mm). The low-LET dose reduces tumor cell survival by a factor of (Formula presented.). Conclusions: The low-LET dose in Alpha DaRT can be modeled by conventional MC techniques with appropriate leakage corrections to the source activity. For 3 (Formula presented.) Ci/cm (Formula presented.) Ra sources, the contribution of the low-LET dose can reduce cell survival inside the tumor by up to two orders of magnitude. The low-LET dose to surrounding healthy tissue is negligible. Increasing source activities by a factor of 5 can bring the low-LET dose itself to therapeutic levels, in addition to the high-LET dose contributed by alpha particles, leading to a “self-boosted” Alpha DaRT configuration, and potentially allowing to increase the lattice spacing.