A model of radiation action based on nanodosimetry and the application to ultra-soft X-rays

Abstract

A radiation action model based on nanodosimetry is presented. It is motivated by the finding that the biological effects of various types of ionizing radiation lack a consistent relation with absorbed dose. It is postulated that the common fundamental cause of these effects is the production of elementary sublesions (DSB), which are created at a rate that is proportional to the probability to produce more than two ionisations within a volume of 10 base pairs of the DNA. The concepts of nanodosimetry allow for a quantitative characterization of this process in terms of the cumulative probability F2. The induced sublesions can interact in two ways to produce lethal damage. First, if two or more sublesions accumulate in a locally limited spherical volume of 3-10 nm in diameter, clustered DNA damage is produced. Second, consequent interactions or rearrangements of some of the initial damage over larger distances ( µm) can produce additional lethal damage. From the comparison of theoretical predictions deduced from this concept with experimental data on relative biological effectiveness, a cluster volume with a diameter of 7.5 nm could be determined. It is shown that, for electrons, the predictions agree well with experimental data over a wide energy range. The only free parameter needed to model cell survival is the intersection cross-section which includes all relevant cell-specific factors. Using ultra-soft X-rays it could be shown that the energy dependence of cell survival is directly governed by the nanodosimetric characteristics of the radiation track structure. The cell survival model derived in this work exhibits exponential cell survival at a high dose and a finite gradient of cell survival at vanishing dose, as well as the dependence on dose-rate.

First measurements of ionization cluster‐size distributions with a compact nanodosimeter

“…Spherical sensitive volumes have the advantage of being independent of the direction of the incident particle. With respect to the use of cluster size distributions in modeling biological damages, cell survival or the relative biological effectiveness, such as in a nanodosimetric radiation action model, 1 spherical volumes are preferred. In addition, spherical volumes are also preferred when Monte Carlo methods are used to obtain cluster size distributions (or parameters derived from the cluster size distribution) in macroscopic volumes for optimizing treatment plans (for an example see Vasi et al 28 ).…”

“…A common fundamental cause of biological effects is the productions of double-strand breaks which correlate with the probability to produce ionizations within a volume of 10 base pairs of DNA. [1][2][3][4] The nanodosimetric quantity, which is measured in a DNA-sized volume, is the number of ionizations ν produced by single traversing charged particles of specified radiation quality, which is described by a probability distribution PðνÞ.…”

“…9 The simultaneous optimization of RBE-weighted dose and nanodosimetric quantities in carbon-ion treatment plans was proposed by Burigo et al 10 A model of radiation action based on nanodosimetric quantities has been developed by Besserer and Schneider. 1,[11][12][13] It was postulated that biological effects are caused by the production of elementary sublesions (DSBs) which are proportional to the nanodosimetric cumulative probability to create at least two ionizations. An expression for the relative biological effectiveness was derived and theoretical results were compared to experimental RBE-values.…”

“…The aim of nanodosimetry is to provide physical measurements of a quantity which describes biological effects of ionizing radiation better than conventional absorbed dose measurements. A common fundamental cause of biological effects is the productions of double‐strand breaks which correlate with the probability to produce ionizations within a volume of 10 base pairs of DNA 1–4 . The nanodosimetric quantity, which is measured in a DNA‐sized volume, is the number of ionizations produced by single traversing charged particles of specified radiation quality, which is described by a probability distribution .…”

Investigation into the foundations of the track-event theory of cell survival and the radiation action model based on nanodosimetry

“…A low-dose approximation of the fundamental model equation was shown to be equivalent to the commonly used linear-quadratic model and to have a dose dependence that matches the experimentally observed exponential dose dependence at higher doses (Besserer and Schneider 2015a). In later work, the parameters of the model have been related to nanodosimetry (Schneider et al 2016(Schneider et al , 2017(Schneider et al , 2019, and recently the TET has been developed into a radiation action model based on nanodosimetry (RAMN) that tried to resolve the shortcomings of the original TET model (Schneider et al 2020).…”