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Electron emission spectra of gold nanoparticles (AuNPs) after photon interaction were measured over the energy range between 50 eV and 9500 eV to provide reference data for Monte Carlo radiation-transport simulations. Experiments were performed with the HAXPES spectrometer at the PETRA III high-brilliance beamline P22 at DESY (Hamburg, Germany) for photon energies below and above each of the gold L-edges, i.e., at 11.9 keV, 12.0 keV, 13.7 keV, 13.8 keV, 14.3 keV, and 14.4 keV. The study focused on a sample with gold nanoparticles with an average diameter of 11.0 nm on a thin carbon foil. Additional measurements were performed on a sample with 5.3 nm gold nanoparticles and on reference samples of gold and carbon foils. Further measurements were made to calibrate the photon flux monitor, to characterize the transmission function of the electron spectrometer and to determine the size of the photon beam. This allowed the determination of the absolute values of the spectral particle radiance of secondary electrons per incident photon flux. The paper presents the experimental and raw data analysis procedures, reviews the data obtained for the nanoparticle samples and discusses their limitations., Revised manuscript after peer review; 21 pages, 15 Figures, 6 Tables plus 4 Supplements with altogether 14 pages, 16 figures, 2 tables

Organized by the European Radiation Dosimetry Group (EURADOS), a Monte Carlo code intercomparison exercise was conducted where participants simulated the emitted electron spectra and energy deposition around a single gold nanoparticle (GNP) irradiated by X-rays. In the exercise, the participants scored energy imparted in concentric spherical shells around a spherical volume filled with gold or water as well as the spectral distribution of electrons leaving the GNP. Initially, only the ratio of energy deposition with and without GNP was to be reported. During the evaluation of the exercise, however, the data for energy deposition in the presence and absence of the GNP were also requested. A GNP size of 50 nm and 100 nm diameter was considered as well as two different X-ray spectra (50 kVp and 100kVp). This introduced a redundancy that can be used to cross-validate the internal consistency of the simulation results. In this work, evaluation of the reported results is presented in terms of integral quantities that can be benchmarked against values obtained from physical properties of the radiation spectra and materials involved. The impact of different interaction cross-section datasets and their implementation in the different Monte Carlo codes is also discussed., Comment: 16 pages, 10 Figures, 1 Table. Accepted manuscript after minor revisions contained an institution without affiliated author

Electron emission spectra of a thin gold foil after photon interaction were measured over the energy range between 50 eV and 9500 eV to provide reference data for Monte Carlo radiation-transport simulations. Experiments were performed with the HAXPES spectrometer at the PETRA III high-brilliance beamline P22 at DESY (Hamburg, Germany) for photon energies just below and above each of the gold L-edges, i.e., at 11.9 keV, 12.0 keV, 13.7 keV, 13.8 keV, 14.3 keV, and 14.4 keV. The data were analyzed to obtain the absolute values of the particle radiance of the emitted electrons per incident photon flux. Simulations of the experiment were performed using the Monte Carlo radiation-transport codes Penelope and Geant4. Comparison of the measured and simulated results shows good qualitative agreement. When simulation results are convolved with curves that take into account the effect of lifetime broadening, line shapes of photoelectron and Auger peaks similar to those observed experimentally are obtained. On an absolute scale, the experiments tend to give higher electron radiance values at the lower photon energies studied as well as at the higher photon energies for electron energies below the energy of the Au L3 photoelectron. This is attributed to the linear polarization of the photon beam in the experiments which is not considered in the simulation codes., Comment: Revised manuscript after peer review, 13 pages, 9 figures

The production of two double strand breaks in spatially separated locations on the DNA molecule can cause the loss of a whole DNA loop, which can be of substantial length depending on the geometrical position of the two damaged sites and depends on the degree of correlation between ionisation clusters formed in sites of several nanometres in size. In the first part of this paper, nanodosimetric measurements of alpha particle tracks in 1.2 mbar H2O, 1.2 mbar C3H8 and 1.2 mbar C4H8O with the PTB ion counter nanodosimeter were reported. In this second part, the focus is on the geometrical characterisation of the two sites simulated with the nanodosimeter in the three target gases and on the comparison of the measurement results with Monte Carlo simulations. The measurements in 1.2 mbar C3H8 were simulated with a version of the track structure code PTra dedicated to modelling the PTB ion counter nanodosimeter. Further simulations were performed with Geant4-DNA for 241Am alpha particle tracks in liquid water. Simulations of the measurements and the actual measurement results are found to be in good agreement for the investigated irradiation geometries., 31 pages, 13 figures, 8 tables

Particle & particle systems characterization 39(11), 2200136 (2022). doi:10.1002/ppsc.202200136, Electron emission cross sections of gold nanoparticles (AuNPs) are important for assessing their radiosensitizing effects from ionizing radiation using Monte Carlo simulations. Measurements of these data require samples of sufficiently large area density, homogeneous nanoparticle distribution, and a mechanically stable sample holder to ensure a low background signal. While several methods exist for the deposition of nanoparticles, there is little information regarding the deposition of AuNPs in an aqueous solution onto a self-supporting film. The aim of this is to find suitable preparation techniques for AuNP samples which fulfill the above requirements. AuNP samples are produced using different deposition techniques and a 50 nm-thick carbon foil as the substrate. These samples are characterized with respect to the size and spatial distribution of AuNPs using a scanning electron microscope. The drop-casting technique yields the best results, while those obtained with the spin-coater technique are less reproducible regarding sample stability. The microdrop method is deemed unsuitable due to its tendency to form AuNP clusters. Measurements conducted with a synchrotron radiation source, as well as with protons and electrons, confirm the suitability of these samples for studying electron emission spectra of AuNPs for different radiation types., Published by Wiley-VCH, Weinheim

Organized by Working Group 6 "Computational Dosimetry" of the European Radiation Dosimetry Group (EURADOS), a group of intercomparison exercises was conducted in which participants were asked to solve predefined problems in computational dosimetry. The results of these comparisons were published in a series of articles in this virtual special issue of Radiation Measurements. This paper reviews the experience gained from the various exercises and highlights the resulting conclusions for future exercises, as well as regarding the state of the art and the need for development in terms of quality assurance for computational dosimetry techniques., Comment: 17 Pages, 6 Figures, submitted to Radiat. Meas

A surface chemical analysis of 12 nm diameter gold nanoparticles (AuNPs) coated with polyethylene glycol (PEG)-11-mercaptoundecanoic acid (MUA) is performed by means of X-ray photoelectron spectroscopy (XPS). For this purpose, the PEGMUA-coated AuNPs are deposited using two different deposition techniques, drop-casting or spin-coating, on a thin-film carbon substrate. The measurements show that AuNPs are present in the +I oxidation state due to the synthesis process of the coated AuNPs, and in the Au(0) oxidation state. Carbon and oxygen contaminations are detected on both the coating surface and carbon substrate. While sputtering of the sample with argon enables the removal of carbon and oxygen contaminations, it also removes part of the coating on the sample surface. The two deposition methods, however, do not cause any chemical structural changes to the nanoparticles.

This work aims at carving out more clearly 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 in the literature for consideration of repair within the TET is based on the assumption that DNA lesions induced by different tracks are repaired independently and that 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 a 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., Accepted version of the manuscript including supplements

Results of a Monte Carlo code intercomparison exercise for simulations of the dose enhancement from a gold nanoparticle (GNP) irradiated by X-rays have been recently reported. To highlight potential differences between codes, the dose enhancement ratios (DERs) were shown for the narrow-beam geometry used in the simulations, which leads to values significantly higher than unity over distances in the order of several tens of micrometers from the GNP surface. As it has come to our attention that the figures in our paper have given rise to misinterpretation as showing 'the' DERs of GNPs under diagnostic X-ray irradiation, this article presents estimates of the DERs that would have been obtained with realistic radiation field extensions and presence of secondary particle equilibrium (SPE). These DER values are much smaller than those for a narrow-beam irradiation shown in our paper, and significant dose enhancement is only found within a few hundred nanometers around the GNP. The approach used to obtain these estimates required the development of a methodology to identify and, where possible, correct results from simulations whose implementation deviated from the initial exercise definition. Based on this methodology, literature on Monte Carlo simulated DERs has been critically assessed., 15 pages, 9 figures, 4 tables, accepted manuscript in Physica Medica

In recent years, several approaches have been proposed to provide an understanding of the enhanced relative biological effectiveness of ion beams based on multi-scale models of their radiation effects. Among these, the BioQuaRT project was the only one which focused on developing metrology for a multi-scale characterization of particle track structure. The progress made within the BioQuaRT project has motivated the formation of a department 'Radiation Effects' at PTB dedicated to metrological research on ionizing radiation effects. This paper gives an overview of the department's present research directions and shortly discusses ideas for the future development of metrology related to biological effects of ion beams that are based on a stakeholder consultation.

Within EURADOS Working Group 6 'Computational Dosimetry', the micro and nanodosimetry task group 6.2 has recently conducted a Monte Carlo (MC) exercise open to participants around the world. The aim of this exercise is to quantify the contribution to the uncertainty of micro and nanodosimetric simulation results arising from the use of different electron-impact cross-sections, and hence physical models, employed by different MC codes (GEANT4-DNA, PENELOPE, MCNP6, FLUKA, NASIC and PHITS). Comparison of the participants' simulation results for both micro and nanodosimetric quantities using different MC codes was the first step of the exercise. The deviation between results is due to different cross-sections but also different tracking methods and particle transport cut-off energies. The second step of the exercise will involve using identical cross-section datasets to account only for the other variations in the first step, thus enabling the determination of the uncertainty contribution due to different cross-sections. This paper presents a comparison of the MC simulation results obtained in the first part of the exercise. For the microdosimetric simulations, particularly in the configuration where the electron source is contained within the micrometric target, the choice of MC code has a small influence on the results. For the nanodosimetric results, on the other hand, the mean ionisation cluster size distribution (ICSD) was sensitive to the physical models used in the MC codes. The ICSD was therefore chosen to study the influence of different cross-section data on the uncertainty of simulation results.

International audience; Ionizing radiation is a peculiar perturbation when it comes to damage to biological systems it proceeds through discrete energy depositions, over a short temporal scale and a spatial scale critical for subcellular targets as DNA, whose damage complexity determines the outcome of the exposure. This lies at the basis of the success of track structure (and nanodosimetry) and microdosimetry in radiation biology. However, such reductionist approaches cannot account for the complex network of interactions regulating the overall response of the system to radiation, particularly when effects are manifest at the supracellular level and involve long times. Systems radiation biology is increasingly gaining ground, but the gap between reductionist and holistic approaches is becoming larger. This paper presents considerations on what roles track structure and microdosimetry can have in the attempt to fill this gap, and on how they can be further exploited to interpret radiobiological data and inform systemic approaches. © The Author(s) 2018. Published by Oxford University Press.

Working Group (WG) 6 ‘Computational Dosimetry’ of the European Radiation Dosimetry Group promotes good practice in the application of computational methods for radiation dosimetry in radiation protection and the medical use of ionising radiation. Its cross-sectional activities within the association cover a large range of current topics in radiation dosimetry, including more fundamental studies of radiation effects in complex systems. In addition, WG 6 also performs scientific research and development as well as knowledge transfer activities, such as training courses. Monte Carlo techniques, including the use of anthropomorphic and other numerical phantoms based on voxelised geometrical models, play a strong part in the activities pursued in WG 6. However, other aspects and techniques, such as neutron spectra unfolding, have an important role as well. A number of intercomparison exercises have been carried out in the past to provide information on the accuracy with which computational methods are applied and whether best practice is being followed. Within the exercises that are still ongoing, the focus has changed towards assessing the uncertainty that can be achieved with these computational methods. Furthermore, the future strategy of WG 6 also includes an extension of the scope toward experimental benchmark activities and evaluation of cross-sections and algorithms, with the vision of establishing a gold standard for Monte Carlo methods used in medical and radiobiological applications.

Since 2012, the European Radiation Dosimetry Group (EURADOS) has developed its Strategic Research Agenda (SRA), which contributes to the identification of future research needs in radiation dosimetry in Europe. Continued scientific developments in this field necessitate regular updates and, consequently, this paper summarises the latest revision of the SRA, with input regarding the state of the art and vision for the future contributed by EURADOS Working Groups and through a stakeholder workshop. Five visions define key issues in dosimetry research that are considered important over at least the next decade. They include scientific objectives and developments in (i) updated fundamental dose concepts and quantities, (ii) improved radiation risk estimates deduced from epidemiological cohorts, (iii) efficient dose assessment for radiological emergencies, (iv) integrated personalised dosimetry in medical applications and (v) improved radiation protection of workers and the public. This SRA will be used as a guideline for future activities of EURADOS Working Groups but can also be used as guidance for research in radiation dosimetry by the wider community. It will also be used as input for a general European research roadmap for radiation protection, following similar previous contributions to the European Joint Programme for the Integration of Radiation Protection Research, under the Horizon 2020 programme (CONCERT). The full version of the SRA is available as a EURADOS report (www.eurados.org).

The stopping power of liquid water was measured for carbon ions with energies in the Bragg peak region using the inverted Doppler shift attenuation method. Among the semiempirical data, the results of this work agree best with the data recommended in the Errata and Addendum of ICRU Report No. 73, which is based on an I value of 78 eV for water. The agreement was worse when the present results were compared to the newer recommendation of the ICRU published in ICRU Report No. 90. The srim code seems to slightly overestimate the stopping power of water for carbon ions above 3 MeV. A semiexperimental stopping power of water for α particles was derived from the present results using the theoretical ratio between the stopping powers of water for carbon ions and α particles computed by means of the casp code. These values agree well with the experimental data for α particles within the uncertainties.

International audience; This roadmap outlines the potential roles of metallic nanoparticles (MNPs) in the field of radiation therapy. MNPs made up of a wide range of materials (from Titanium, Z = 22, to Bismuth, Z = 83) and a similarly wide spectrum of potential clinical applications, including diagnostic, therapeutic (radiation dose enhancers, hyperthermia inducers, drug delivery vehicles, vaccine adjuvants, photosensitizers, enhancers of immunotherapy) and theranostic (combining both diagnostic and therapeutic), are being fabricated and evaluated. This roadmap covers contributions from experts in these topics summarizing their view of the current status and challenges, as well as expected advancements in technology to address these challenges.

An intercomparison of microdosimetric and nanodosimetric quantities simulated Monte Carlo codes is in progress with the goal of assessing the uncertainty contribution to simulated results due to the uncertainties of the electron interaction cross-sections used in the codes. In the first stage of the intercomparison, significant discrepancies were found for nanodosimetric quantities as well as for microdosimetric simulations of a radiation source placed at the surface of a spherical water scoring volume. This paper reports insight gained from further analysis, including additional results for the microdosimetry case where the observed discrepancies in the simulated distributions could be traced back to the difference between track-structure and condensed-history approaches. Furthermore, detailed investigations into the sensitivity of nanodosimetric distributions to alterations in inelastic electron scattering cross-sections are presented which were conducted in the lead up to the definition of an approach to be used in the second stage of the intercomparison to come. The suitability of simulation results for assessing the sought uncertainty contributions from cross-sections is discussed and a proposed framework is described., 23 pages, 7 figures, 5 tables plus 3 supplementary figures

Low-energy electron-induced reactions in hydrated molecular complexes are important in various fields ranging from the Earth’s environment to radiobiological processes including radiation therapy. Nevertheless, our understanding of the reaction mechanisms in particular in the condensed phase and the role of water in aqueous environments is incomplete. Here we use small hydrogen-bonded pure and mixed dimers of the heterocyclic molecule tetrahydrofuran (THF) and water as models for biochemically relevant systems. For electron-impact-induced ionization of these dimers, a molecular ring-break mechanism is observed, which is absent for the THF monomer. Employing coincident fragment ion mass and electron momentum spectroscopy, and theoretical calculations, we find that ionization of the outermost THF orbital initiates significant rearrangement of the dimer structure increasing the internal energy and leading to THF ring-break. These results demonstrate that the local environment in form of hydrogen-bonded molecules can considerably affect the stability of molecular covalent bonds., Reactions induced by low-energy electrons in hydrated systems are central to radiation therapy, but a full understanding of their mechanism is lacking. Here the authors investigate the electron-impact induced ionization and subsequent dissociation of tetrahydrofuran, model for biochemically relevant systems, in a micro-solvated environment.

The European Radiation Dosimetry Group (EURADOS) is a network of organizations and scientists promoting research and development in the dosimetry of ionizing radiation, contributing to harmonization in dosimetry practice across Europe, and offering education and training in areas relevant for dosimetry. As a registered non-profit association under German law, EURADOS is currently running eight active working groups (WGs): WG2 on “Harmonization of Individual Monitoring”, WG3 on “Environmental Dosimetry”, WG6 on “Computational Dosimetry”, WG7 on “Internal Dosimetry”, WG9 on “Dosimetry in Radiotherapy”, WG10 on “Retrospective Dosimetry”, WG11 on “Dosimetry in High-Energy Radiation Fields”, and WG12 on “Dosimetry in Medical Imaging”. This paper presents recent scientific results obtained within these working groups, and additionally highlights the role of EURADOS as an organization which contributes to the development of a systematic strategy of radiation protection research in Europe.

Corrigendum to “Intercomparison of dose enhancement ratio and secondary electron spectra for gold nanoparticles irradiated by X-rays calculated using multiple Monte Carlo simulation codes” [Phys. Med. 69 (2020) 147–163] (Physica Medica (2020) 69 (147–163), (S1120179719305320), (10.1016/j.ejmp.2019.12.011)); International audience; Purpose: Targeted radiation therapy has seen an increased interest in the past decade. In vitro and in vivo experiments showed enhanced radiation doses due to gold nanoparticles (GNPs) to tumors in mice and demonstrated a high potential for clinical application. However, finding a functionalized molecular formulation for actively targeting GNPs in tumor cells is challenging. Furthermore, the enhanced energy deposition by secondary electrons around GNPs, particularly by short-ranged Auger electrons is difficult to measure. Computational models, such as Monte Carlo (MC) radiation transport codes, have been used to estimate the physical quantities and effects of GNPs. However, as these codes differ from one to another, the reliability of physical and dosimetric quantities needs to be established at cellular and molecular levels, so that the subsequent biological effects can be assessed quantitatively. Methods: In this work, irradiation of single GNPs of 50 nm and 100 nm diameter by X-ray spectra generated by 50 and 100 peak kilovoltages was simulated for a defined geometry setup, by applying multiple MC codes in the EURADOS framework. Results: The mean dose enhancement ratio of the first 10 nm-thick water shell around a 100 nm GNP ranges from 400 for 100 kVp X-rays to 600 for 50 kVp X-rays with large uncertainty factors up to 2.3. Conclusions: It is concluded that the absolute dose enhancement effects have large uncertainties and need an inter-code intercomparison for a high quality assurance; relative properties may be a better measure until more experimental data is available to constrain the models.

There is a continued need for further clarification of various aspects of radiation-induced chromosomal aberration, including its correlation with radiation track structure. As part of the EMRP joint research project, Biologically Weighted Quantities in Radiotherapy (BioQuaRT), we performed experimental and theoretical analyses on chromosomal aberrations in Chinese hamster ovary cells (CHO-K1) exposed to α particles with final energies of 5.5 and 17.8 MeV (absorbed doses: ∼2.3 Gy and ∼1.9 Gy, respectively), which were generated by the microbeam at the Physikalisch-Technische Bundesanstalt (PTB) in Braunschweig, Germany. In line with the differences in linear energy transfer (approximately 85 keV/μm for 5.5 MeV and 36 keV/μm for 17.8 MeV α particles), the 5.5 MeV α particles were more effective than the 17.8 MeV α particles, both in terms of the percentage of aberrant cells (57% vs. 33%) and aberration frequency. The yield of total aberrations increased by a factor of ∼2, although the increase in dicentrics plus centric rings was less pronounced than in acentric fragments. The experimental data were compared with Monte Carlo simulations based on the BIophysical ANalysis of Cell death and chromosomal Aberrations model (BIANCA). This comparison allowed interpretation of the results in terms of critical DNA damage [cluster lesions (CLs)]. More specifically, the higher aberration yields observed for the 5.5 MeV α particles were explained by taking into account that, although the nucleus was traversed by fewer particles (nominally, 11 vs. 25), each particle was much more effective (by a factor of ∼3) at inducing CLs. This led to an increased yield of CLs per cell (by a factor of ∼1.4), consistent with the increased yield of total aberrations observed in the experiments.

International audience; This work provides the first cross section data set of DNA constituents for an impact of electrons in the energy range between about 10 eV and 1 keV on a DNA target. The data set is designed for an implementation in Monte Carlo simulations and consists of model functions, taking into account elastic scattering, ionization and excitation interactions with the DNA constituents tetrahydrofuran, trimethylphosphate, pyrimidine and purine. It was developed on the basis of experimentally determined absolute differential and total scattering cross sections in accordance with the available literature data. The data set will be available in the Geant4-DNA toolkit to allow secondary electron transport in a DNA-like medium down to the ionization threshold. © 2016 Elsevier Ltd

Advances in accelerator technology, which have enabled conforming radiotherapy with charged hadronic species, have brought benefits as well as potential new risks to patients. To better understand the effects of ionizing radiation on tumor and surrounding tissue, it is important to investigate and quantify the relationship between energy deposition at the nanometric scale and the initial biological events. Monte Carlo track structure simulation codes provide a powerful tool for investigating this relationship; however, their success and reliability are dependent on their improvement and development accordingly to the dedicated biological data to which they are challenged. For this aim, a microbeam facility that allows for fluence control, down to one ion per cell nucleus, was used to evaluate relative frequencies of DNA damage after interaction between the incoming ion and DNA according to radiation quality. Primary human cells were exposed to alpha particles of three different energies with respective linear energy transfers (LETs) of approximately 36, 85 or 170 keV·µm-1 at the cells' center position, or to protons (19 keV·µm-1). Statistical evaluation of nuclear foci formation (53BP1/γ-H2AX), observed using immunofluorescence and related to a particle traversal, was undertaken in a large population of cell nuclei. The biological results were adjusted to consider the factors that drive the experimental uncertainties, then challenged with results using Geant4-DNA code modeling of the ionizing particle interactions on a virtual phantom of the cell nucleus with the same mean geometry and DNA density as the cells used in our experiments. Both results showed an increase of relative frequencies of foci (or simulated DNA damage) in cell nuclei as a function of increasing LET of the traversing particles, reaching a quasi-plateau when the LET exceeded 80-90 keV·µm-1. For the LET of an alpha particle ranging from 80-90 to 170 keV·µm-1, 10-30% of the particle hits did not lead to DNA damage inducing 53BP1 or γ-H2AX foci formation.

Biological effectiveness of a certain absorbed dose of ionizing radiation depends on the radiation quality, i. e. the spectrum of ionizing particles and their energy distribution. As has been shown in several studies, the biological effectiveness is related to the pattern of energy deposits on the microscopic scale, the so-called track structure. Clusters of lesions in the DNA molecule within site sizes of few nanometers play a particular role in this context. This work presents a brief overview of nanodosimetric approaches to relate biological effects with track structure derived quantities and experimental techniques to derive such quantities.

Doubly differential electron-impact ionization cross sections of propane were comprehensively measured for electron energies between 30 eV and 1 keV as a function of secondary electron energies and emission angles. The measurements were carried out for secondary electron energies from 3 eV to about half of the primary energy and for emission angles between 10° and 135°. To facilitate practical application and implementation of the data into numerical codes used for radiation transport calculations, a semi-empirical formula was constructed on the basis of existing models. The semi-empirical formula is capable of reproducing the measured data well over a wide energy and angular range. Singly differential ionization cross sections were obtained by the integration of the experimental data over the emission angles and total ionization cross sections (TICSs) were determined by the integration of the data both over the emission angles and secondary electron energies. They were compared to the theoretical results calculated using the binary-encounter-Bethe (BEB) model. The calculated TICSs mostly agree with the data published by other groups within the experimental uncertainties.

High-Z nanomaterials, e.g. gold nanoparticles (GNPs), are being investigated worldwide for potential application in radiation imaging and therapy. Photon irradiation of cells containing GNP was shown to produce enhanced DNA damage which is believed to be related to the increased secondary electron (SE) yield and ionization density. In this work, an algorithm was developed for simulating the physical radiation damage inside the nucleus of a spherical cell model for the case of uniformly distributed GNPs within the cytoplasm. Previously calculated energy spectra of SE emerging from a single NP irradiated with different photon sources are used as input to obtain the SE energy spectrum at the surface of the cell nucleus. In a second step, the SE transport inside the cell nucleus is simulated with a track structure Monte Carlo code to obtain the spatial distribution of ionizations. The preliminary results presented here show that the developed algorithm allows for a fast calculation of the SE spectra at the cell nucleus surface, thus enabling a more realistic assessment of the ionization density inside the cell nucleus than that obtained by the simulation of a single GNP. Furthermore, the algorithm can be easily adapted to investigate both the effect of GNP clustering and the impact of GNP-GNP interactions on SE spectra.

In nanodosimetry, the ionization component of charged particle track structure is characterized by measuring the frequency distribution of ionizations in target volumes that simulate nanometric sites in liquid water. For the Ion Counter nanodosimeter at PTB, the sensitive volume is defined by the electrical field and the extraction aperture. In this paper, a procedure is presented to define a cylindrical effective measurement target based on the second moments of the detection efficiency map. An analytical model of the efficiency map is developed to investigate the dependence of the simulated site size on the nanodosimeter's operating parameters. Within the limits of the simplifying assumptions, the model gives a reasonable approximation of the efficiency map.

The simultaneous occurrence of two double-strand breaks in spatially separated locations on the DNA molecule can cause the loss of a whole DNA loop. The length of the lost DNA loop depends on the geometrical position of the two damaged sites and on the degree of damage in sites of several nanometres in size. As they are more prone to produce complex ionisation clusters in such sites, densely ionising charged particles are expected to produce more spatially correlated ionisation clusters than electrons and photons. In this work, correlations in the production of ionisation clusters in two spatially separated sites were investigated for the first time in detail by nanodosimetric measurements in 1.2 mbar H2O, 1.2 mbar C3H8 and 1.2 mbar C4H8O using alpha particles from a 241Am source. The results show that there are irradiation geometries where only weak correlation exists between the probabilities for ionisation clusters in the two spatially separated sites, e. g. when the primary beam passes one site centrally. In general, however, the two probability distributions are not statistically independent, for instance if both sites are irradiated in a broad beam.

This work presents a detailed investigation into the nanodosimetric properties of the track structure of protons in water at energies relevant for proton radiotherapy. The ionization component of the tracks had been simulated in previous work using Geant4-DNA for proton start energies between 1 MeV and 100 MeV. From the simulation results, the frequency distribution of ionization clusters formed in nanometric target volumes was obtained in dependence of the impact parameter of the proton trajectory with respect to the target center. In the track core, targets of cylindrical shape and a size comparable to a short segment of DNA were used for scoring ionization cluster size distributions. For the penumbra region, three different options for defining the cylinder shell sectors were investigated, with each cylinder shell sector volume the same as the cylinder target volume. The radial distributions were numerically integrated to obtain the effective track cross sections with respect to different nanodosimetric parameters. Graphically displaying the radial dependence in a similar way as microdosimetric distributions allowed elucidating the contribution of different radial distances to the overall radial integral of the quantities under consideration. Furthermore, it was tested how well the radial dependence of the nanodosimetric parameters could be fitted with a model function derived in literature for the radial energy deposition in proton tracks. It was found that this model function allows describing only the radial dependence of the total frequency of nanometric targets where ionizations occur. The deviation from a 1/r2-dependence of the radial dependence of the frequency of targets receiving more than a minimum number of ionizations (exceeding one) includes a second peak centred around 10 nm radial distance from the proton trajectory.

This work presents an attempt to addressing the issue of RBE variation in a spread-out Bragg peak (SOBP) of protons based on nanodosimetric track structure analysis. Ionization track structure has been simulated using Geant4-DNA for protons of 100 MeV initial energy propagating in water. The frequency distribution of ionization clusters formed in target volumes corresponding to a 10 base-pairs segment of DNA was obtained as a function of the radial distance between target and proton trajectory for a set of positions along the proton path. Radial dependence of nanodosimetric parameters was analysed using a heuristic model function to obtain an effective track cross section (ETCS) as a function of the proton's residual range. The results were convolved with weighted range distributions suggested in literature for constructing a SOBP. The ETCS shows an increase in the distal end region of the SOBP in qualitative agreement with radiobiological observations of enhanced cell damage in this region. The results demonstrate that nanodosimetric track characteristics may be used for qualitatively predicting the variation of the probability for induction of lethal lesions in cells.

Progress in the field of ionising radiation (IR) metrology achieved in the BioQuaRT project raised the question to what extent radiobiological investigations would benefit from metrological support of the applied methodologies. A panel of experts from the medical field, fundamental research and radiation protection attended a workshop at Physikalisch-Technische Bundesanstalt to consult on metrology needs related to biological radiation effects. The panel identified a number of metrological needs including the further development of experimental and computational techniques for micro- and nanodosimetry, together with the determination of related fundamental material properties and the establishment of rigorous uncertainty budgets. In addition to this, a call to develop a metrology support for assisting quality assurance of radiobiology experiments was expressed. Conclusions from the workshop were presented at several international conferences for further discussion with the scientific community and stakeholder groups that led to an initiative within the metrology community to establish a European Metrology Network on biological effects of IR.

Ionisation cluster size distributions produced in the sensitive volume of an ion-counting wall-less nanodosimeter by monoenergetic carbon ions with energies between 45 MeV and 150 MeV were measured at the TANDEM-ALPI ion accelerator facility complex of the LNL INFN in Legnaro. Those produced by monoenergetic helium ions with energies between 2 MeV and 20 MeV were measured at the accelerator facilities of PTB and with a 241Am alpha particle source. C3H8 was used as the target gas. The ionisation cluster size distributions were measured in narrow beam geometry with the primary beam passing the target volume at specified distances from its centre, and in broad beam geometry with a fan-like primary beam. By applying a suitable drift time window, the effective size of the target volume was adjusted to match the size of a DNA segment. The measured data were compared with the results of simulations obtained with the PTB Monte Carlo code PTra. Before the comparison, the simulated cluster size distributions were corrected with respect to the background of additional ionisations produced in the transport system of the ionised target gas molecules. Measured and simulated characteristics of the particle track structure are in good agreement for both types of primary particles and for both types of the irradiation geometry., 25 pages, 20 figures

The ability of DNA to conduct electric current has been the topic of numerous investigations over the past few decades. Those investigations indicate that this ability is dependent on the molecular structure of the DNA. Radiation-induced damages, which lead to an alteration of the molecular structure, should therefore change the electrical impedance of a DNA molecule. In this paper, the damage due to ionising radiation is shown to have a direct effect on the electrical transport properties of DNA. Impedance measurements of DNA samples were carried out by an AC impedance spectrometer before, during and after irradiation. The samples comprised of DNA segments, which were immobilized between gold electrodes with a gap of 12 μm. The impedance of all DNA samples exhibited rising capacitive behaviour with increasing absorbed dose.

Nanodosimetry is a branch of dosimetry for investigation and modeling of the interaction pattern of ionizing radiation in nanometre site-sizes (at unit density), which dates back to the 1970's (Pszona S. A track ion counter. Proceedings of Fifth Symposium on Microdosimetry EUR 5452 d-e-f, Published by the Commission of the European Communities, Luxemburg, pp. 1107-1122 (1976)). To date, the different experimental approaches have lead to developing of three fully functional nanodosimeters: the Jet Counter operated at NCBJ, the Ion Counter operated at PTB and Startrack Counter operated at INFN-LNL. Descriptions of each nanodosimeter as well as of the techniques used to investigate the track structure of ionizing particles are presented.

The biological action of ionizing charged particles is initiated at the DNA level, and the effectiveness with which the initial physical effect changes into measurable biological damage is likely ruled by the stochastics of ionizations produced by the incident ions in subcellular nanometric volumes. Based on this hypothesis, experimental nanodosimetry aims at establishing a new concept of radiation quality that builds on measurable characteristics of the particle track structure at the nanometer scale. Three different nanodosimetric detection systems have been developed to date that allow measurements of the number of ionizations produced by the passage of a primary particle in a nanometer-size gas volume (in unit density scale). Within the Italian project MITRA (MIcrodosimetry and TRAck structure), funded by the Italian Istituto Nazionale di Fisica Nucleare (INFN) and the EMRP Joint Research Project 'BioQuaRT' (Biologically Weighted Quantities in Radiotherapy), experiments have been carried out, in which the frequency distribution of ionizations produced by proton and carbon ion beams of given energy was measured with the three nanodosimetric detectors. Descriptors of the track structure can be derived from these distributions. In particular, the first moment M1, representing the mean number of ionizations produced in the target volume, and the cumulative probability Fk of measuring a number ν ≥ k of ionizations. The correlation between measured nanodosimetric quantities and experimental radiobiological data available in the literature is here presented and discussed.

Within the Italian project MITRA (MIcrodosimetry and TRAck structure), funded by the Italian Istituto Nazionale di Fisica Nucleare (INFN), and the EMRP Joint Research Project “BioQuaRT” (Biologically Weighted Quantities in Radiotherapy), experiments have been carried out at the Tandem–Alpi accelerator facility of Legnaro National Laboratories (LNL), in which the frequency distribution of the number of ionisations produced by proton and carbon ion beams of given energy was measured with the PTB Ion Counter and the LNL StarTrack Counter. Descriptors of the track structure can be derived from these distribution; in particular, the first moment M1, representing the mean number of ionisations produced in the target volume, and the cumulative probabilities Fk of measuring cluster sizes ν ≥ k. Experimental radiobiological data have been compared with nanodosimetric quantities derived from measured ionisation-cluster size distributions. It was found that the cumulative probabilities Fk as a function of M1 behave in the same way as the inactivation cross sections as a function of LET, first increasing with increasing values of M1 and then showing a saturation effect. A comparison of Fk and radiobiological quantities is presented and discussed.

Nanoparticles (NPs) containing high atomic number (high-Z) materials have been shown to enhance the radiobiological effectiveness of ionizing radiation. This effect is often attributed to an enhancement of the absorbed dose in the vicinity of the NPs, based on Monte Carlo simulations that show a significant local enhancement of the energy deposition on the microscopic scale. The results of such simulations may be significantly biased and lead to a severe overestimation of the dose enhancement if the condition of secondary particle equilibrium is not met in the simulation setup. This current work shows an approach to estimate a ‘realistic’ dose enhancement from the results of such biased simulations which is based on published photon interaction data and provides a way for correcting biased results.

In previous investigations using the PTB Ion Counter nanodosimeter, significant deviations for large cluster sizes were found in the comparison between measured and simulated data of ionisation cluster size distributions. These deviations could be explained quantitatively using a simple parametric model for a background of secondary ions, which are produced within the transport system of the target gas ions to the ion detector. To correct for these secondary ions, unfolding procedures were applied to the measured data to remove the effects of this background. However, the parameters of the model describing the background of secondary ions strongly depend on operational parameters of the nanodosimeter, and any change in these operational parameters requires a new characterisation of the model's parameters. In this work, the influence of the nanodosimeter's operational parameters on the background of secondary ions and the collection efficiency of the detected ions was therefore systematically investigated. At the end of this process operational conditions were found where the background of secondary ions is reduced substantially while the effect on the spatial distribution of the collection efficiency is still acceptable. For some beam geometries of particular relevance for radiation biology, cluster size distributions measured with these new operational parameters can be used directly so that the unfolding procedures, and consequently the characterisation of the secondary ion background with respect to the parameters required by the corresponding model used in the unfolding, can be omitted.