Physics and small-scale dosimetry of α $\alpha$ -emitters for targeted radionuclide therapy: The case of 211 At $

BACKGROUND: Monte Carlo simulations have been considered for a long time the gold standard for dose calculations in conventional radiotherapy and are currently being applied for the same purpose in innovative radiotherapy techniques such as targeted radionuclide therapy (TRT). PURPOSE: We present in this work a benchmarking study of the latest version of the Transport d'Ions Lourds Dans l'Aqua & Vivo (TILDA-V ) Monte Carlo track structure code, highlighting its capabilities for describing the full slowing down of α $\alpha$ -particles in water and the energy deposited in cells by α $\alpha$ -emitters in the context of TRT. METHODS: We performed radiation transport simulations of α $\alpha$ -particles (10 keV u - 1 ${\rm u}^{-1}$ -100 MeV u - 1 ${\rm u}^{-1}$ ) in water with TILDA-V and the Particle and Heavy Ion Transport code System (PHITS) version 3.33. We compared the predictions of each code in terms of track parameters (stopping power, range and radial dose profiles) and cellular S-values of the promising radionuclide astatine-211 ( 211 At $^{211}{\rm At}$ ). Additional comparisons were made with available data in the literature. RESULTS: The stopping power, range and radial dose profiles of α $\alpha$ -particles computed with TILDA-V were in excellent agreement with other calculations and available data. Overall, minor differences with PHITS were ascribed to phase effects, that is, related to the use of interaction cross sections computed for water vapor or liquid water. However, important discrepancies were observed in the radial dose profiles of monoenergetic α $\alpha$ -particles, for which PHITS results showed a large underestimation of the absorbed dose compared to other codes and experimental data. The cellular S-values of 211 At $^{211}{\rm At}$ computed with TILDA-V  agreed within 4% with the values predicted by PHITS and MIRDcell. CONCLUSIONS: The validation of the TILDA-V code presented in this work opens the possibility to use it as an accurate simulation tool for investigating the interaction of α $\alpha$ -particles in biological media down to the nanometer scale in the context of medical research. The code may help nuclear medicine physicians in their choice of α $\alpha$ -emitters for TRT. Further research will focus on the application of TILDA-V for quantifying radioinduced damage on the deoxyribonucleic acid (DNA) molecule.

How to explain the sensitivity of DNA double-strand breaks yield to 125I position?

PURPOSE: Auger emitters exhibit interesting features due to their emission of a cascade of short-range Auger electrons. Maximum DNA breakage efficacy is achieved when decays occur near DNA. Studies of double-strand breaks (DSBs) yields in plasmids revealed cutoff distances from DNA axis of 10.5 Å-12 Å, beyond which the mechanism of DSBs moves from direct to indirect effects, and the yield decreases rapidly. Some authors suggested that the average energy deposited in a DNA cylinder could explain such cutoffs. We aimed to study this hypothesis in further detail. MATERIALS AND METHODS: Using the Monte Carlo code CELLDOSE, we investigated the influence of the 125I atom position on energy deposits and absorbed doses per decay not only in a DNA cylinder, but also in individual strands, each modeled as 10 spheres encompassing the fragility sites for phosphodiester bond cleavage. RESULTS: The dose per decay decreased much more rapidly for a sphere in the proximal strand than for the DNA cylinder. For example, when moving the 125I source from 10.5 Å to 11.5 Å, the average dose to the sphere dropped by 43%, compared to only 13% in the case of the cylinder. CONCLUSIONS: Explaining variations in DSBs yields with 125I position should consider the probability of inducing damage in the proximal strand (nearest to the 125I atom). The energy received by fragility sites in this strand is highly influenced by the isotropic (4π) emission of 125I low-energy Auger electrons. The positioning of Auger emitters for targeted radionuclide therapy can be envisioned accordingly.