TRACK EVENT THEORY: A CELL SURVIVAL and RBE MODEL CONSISTENT WITH NANODOSIMETRY

Schneider, Uwe; Vasi, Fabiano; Schmidli, Kevin; Besserer, Jürgen

doi:10.1093/rpd/ncy236

Cited by 10 publications

(33 citation statements)

References 17 publications

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“…The RBE as defined by Eq. ( 9) was derived from a more general formulation as compared to that of Schneider et al (2019) which is somewhat over-simplified.…”

Section: Cell Survival Probabilitymentioning

confidence: 99%

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

Schneider

Vasi

Schmidli

et al. 2020

Radiat Environ Biophys

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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.

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“…The RBE as defined by Eq. ( 9) was derived from a more general formulation as compared to that of Schneider et al (2019) which is somewhat over-simplified.…”

Section: Cell Survival Probabilitymentioning

confidence: 99%

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

Schneider

Vasi

Schmidli

et al. 2020

Radiat Environ Biophys

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“…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.…”

Section: Introductionmentioning

confidence: 99%

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

Vasi

Schneider

2021

Medical Physics

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A nanodosimeter is a type of detector which measures single ionizations in a small gaseous volume in order to obtain ionization cluster size probability distributions for characterization of radiation types. Working nanodosimeter detectors are usually bulky machines which require a lot of space. In this work, the authors present a compact ceramic nanodosimeter detector and report on first measurements of cluster size distributions of 5 MeV alpha particles. Methods: Single ionization measurements are achieved by applying a weak electric field to collect positive ions in a hole in a ceramic plate. Inside the ceramic plate, due to a strong electric field, the ions are accelerated and produce impact-ionizations. The resulting electron avalanche is detected in a read-out electrode. A Bayesian unfolding algorithm is then applied to the experimentally obtained cluster size distributions to reconstruct the true cluster size distributions. Results: Experimentally obtained cluster size distributions by the compact nanodosimeter detector are presented. The reconstructed cluster size distributions agreed well with Monte Carlo simulated cluster size distributions for small volumes (diameter = 2.5 nm). For larger volumes, discrepancies between the reconstructed cluster size distributions and cluster size distributions from Monte Carlo simulations were observed. Conclusions: For the first time, ionization cluster size probability distributions could be obtained by a small and compact nanodosimeter detector. This signifies the achievement of a critical step toward the wide application of nanodosimetric characterization of radiation types including in clinical environments.

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“…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).…”

Section: Introductionmentioning

confidence: 99%

“…This statement seems paradoxical given that for a particular track and a specific target volume, an OTE and a TTE are disjoint alternatives and, hence, statistically dependent. This contradiction arises from the fact that the terms OTE and TTE were used in two different meanings (Besserer and Schneider 2015a, b;Schneider et al 2019). Namely, on the one hand, the effect of a particular track on a cell in the sense stated above, and, on the other hand, for the (multi-event) result of the irradiation on the cell.…”

Section: Introductionmentioning

confidence: 99%

“…To further reduce the number of model parameters, a first attempt was made in Schneider et al (2019) to explicitly relate the TET model parameters and nanodosimetric parameters of track structure. This relation was derived by considering OTEs and TTEs in microscopic sites (named "lethal interaction" volumes) within which DSBs are induced in "basic interaction volumes" (BIVs).…”

Section: Introductionmentioning

confidence: 99%

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

Ngcezu

Rabus

2021

Radiat Environ Biophys

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This work aims at elaborating the basic assumptions behind the “track-event theory” (TET) and its derivate “radiation action model based on nanodosimetry” (RAMN) by clearly distinguishing between effects of tracks at the cellular level and the induction of lesions in subcellular targets. It is demonstrated that the model assumptions of Poisson distribution and statistical independence of the frequency of single and clustered DNA lesions are dispensable for multi-event distributions because they follow from the Poisson distribution of the number of tracks affecting the considered target volume. It is also shown that making these assumptions for the single-event distributions of the number of lethal and sublethal lesions within a cell would lead to an essentially exponential dose dependence of survival for practically relevant values of the absorbed dose. Furthermore, it is elucidated that the model equation used for consideration of repair within the TET is based on the assumption that DNA lesions induced by different tracks are repaired independently. Consequently, the model equation is presumably inconsistent with the model assumptions and requires an additional model parameter. Furthermore, the methodology for deriving model parameters from nanodosimetric properties of particle track structure is critically assessed. Based on data from proton track simulations it is shown that the assumption of statistically independent targets leads to the prediction of negligible frequency of clustered DNA damage. An approach is outlined how track structure could be considered in determining the model parameters, and the implications for TET and RAMN are discussed.

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TRACK EVENT THEORY: A CELL SURVIVAL and RBE MODEL CONSISTENT WITH NANODOSIMETRY

Cited by 10 publications

References 17 publications

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

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

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

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

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