SU-D-137-05: Impact of Dosimetric Uncertainties On the Computed Relative Biological Effectiveness (RBE) of High Linear Energy Transfer (LET) Particles

Abstract

Purpose: Quantify uncertainties in cellular and sub‐cellular dosimetry required for the analysis of biological experiments in which cell cultures are irradiated by charged particles. Assess the impact of dosimetric uncertainties on the computed RBE of high LET charged particles. Methods: Estimates of the frequency‐mean specific energy, lineal energy and absorbed dose per unit fluence (D/Φ) are computed using analytical, deterministic (MCDS) and Monte Carlo (MCNPX and TOPAS/Geant4) methods for representative cell culture geometries. Uncertainties in dosimetric quantities associated with thickness of the culture dish (0.85 mg/cm2 of Melinex) and the location of the nucleus (0–8 urn from the Melinex surface) within a 2 mm layer of culture medium (water) are quantified for a variety of high LET particles (e−, 1H+, 2H+, 3He2 + 4He2 +, and 12C6 +). Results: Uncertainties in D/Φ and related quantities may be as large as 75% for a 4 MeV 4He2 + (range about 27 μm). Substantial differences are seen in dosimetric quantities for all of the considered charged particles with a CSDA range less than about 150 μm. For particles with a CSDA range larger than about 30 μm, dosimetric quantities computed using the deterministic MCDS algorithm are typically within 3% of the estimates obtained with Monte Carlo. The default TOPAS/Geant4 physics parameters sometimes produce estimates of fluence and absorbed dose that differ from the MCDS and MCNPX estimates by as much as 15%. Conclusion: The size and location of the cell nucleus during mitotic cell cycle has a significant impact on the dose delivered to cellular and subcellular targets for short range (high LET) particles. Path and energy straggling have a small impact on deterministic dose quantities for particles with a CSDA range larger than about 30 μm (Z < 6). Dosimetric uncertainties may have a significant impact on the inferred RBE of high LET particles.