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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.
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... Since most of the electrons are ejected with energies below 50 eV, DEA has been regarded as especially relevant to biodamage. 18 In contrast, current physical approaches to measure clustered inelastic events in targets with a DNA size, referred to as nanodosimetry, 19,20 are based on the exclusive measure-ment of ionizing collisions (in gas-phase detectors, which cannot asses the role of indirect chemical events). In this context, it is crucial to precisely determine the relative contribution to clustered DNA damage for carbon ions due to the different direct interaction mechanisms. ...
... Remarkably, it is known that the representation of the measured F k ioniz distributions for ionization events as a function of the average ionization cluster size M 1 ioniz yields a universal distribution independent of the size and characteristics of the particular nanodosimeter, which can be used to predict cell inactivation cross sections. 19,20 Our simulations provide these ionization distributions in nanometric cylinders of liquid water, which mimic DNA targets, at different values of the carbon-ion energy T and the impact parameter r. Figure 5 shows the plot F k ioniz (k = 1, 2, or 3) for ionization in the ranges 0.2 MeV/u to 1 GeV and 0 ≤ r ≤ 100 nm as a function of the average ionization cluster size M 1 ioniz . Results are reported for the two target sizes relevant in evaluating lethal DNA damage, both of which have a diameter of 2.3 nm but a height of 3.4 or 6.8 nm that corresponds to DNA turns of 10 bp (dashed lines) or 20 bp (solid lines), respectively. ...
... Results are reported for the two target sizes relevant in evaluating lethal DNA damage, both of which have a diameter of 2.3 nm but a height of 3.4 or 6.8 nm that corresponds to DNA turns of 10 bp (dashed lines) or 20 bp (solid lines), respectively. Our simulations show a good agreement with nanodosimetric measurements in gas targets in a wide range of M 1 ioniz values, 20 confirming the universal relation F k ioniz vs M 1 ioniz for nanometric liquid water volumes. These data correspond to the impact parameters at which the largest amount of damaging events occur, i.e., for r < 10 nm for every ion energy. ...
Article
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The effective use of swift ion beams in cancer treatment (known as hadrontherapy), as well as appropriate protection in manned space missions, rely on the accurate understanding of the energy delivery to cells that damages their genetic information. The key ingredient characterizing the response of a medium to the perturbation induced by charged particles is its electronic excitation spectrum. By using linear-response time-dependent density functional theory, we obtained the energy and momentum transfer excitation spectrum (the energy-loss function, ELF) of liquid water (the main constituent of biological tissues), which was in excellent agreement with experimental data. The inelastic scattering cross sections obtained from this ELF, together with the elastic scattering cross sections derived by considering the condensed phase nature of the medium, were used to perform accurate Monte Carlo simulations of the energy deposited by swift carbon ions in liquid water and carried away by the generated secondary electrons, producing inelastic events such as ionization, excitation, and dissociative electron attachment (DEA). The latter are strongly correlated with cellular death, which is scored in sensitive volumes with the size of two DNA convolutions. The sizes of the clusters of damaging events for a wide range of carbon-ion energies, from those relevant to hadrontherapy up to those for cosmic radiation, predict with unprecedented statistical accuracy the nature and relative magnitude of the main inelastic processes contributing to radiation biodamage, confirming that ionization accounts for the vast majority of complex damage. DEA, typically regarded as a very relevant biodamage mechanism, surprisingly plays a minor role in carbon-ion induced clusters of harmful events.
... The EMRP project BioQuaRT (4-6) was the first joint research project in IR metrology to take an interdisciplinary approach towards novel dosimetry concepts (based on particle track structure) that account for the impact of radiation quality. The progress made within BioQuaRT comprised new insights into the link between particle track structure and biological effects (7)(8)(9) and substantially augmented methodologies for the analysis of radiobiological data obtained with an ion microbeam (10,11) . An example for the former was the finding that the relation between linear energy transfer (LET) and the radiobiological cross-section for cell inactivation by ion beams is the same as the functional dependence between the mean number of ionisations in a nanometric target (which is related to LET) and the cumulative probabilities for having at least two or three ionisations in such a target volume (8,9) . ...
... The progress made within BioQuaRT comprised new insights into the link between particle track structure and biological effects (7)(8)(9) and substantially augmented methodologies for the analysis of radiobiological data obtained with an ion microbeam (10,11) . An example for the former was the finding that the relation between linear energy transfer (LET) and the radiobiological cross-section for cell inactivation by ion beams is the same as the functional dependence between the mean number of ionisations in a nanometric target (which is related to LET) and the cumulative probabilities for having at least two or three ionisations in such a target volume (8,9) . An example for the latter are radiobiological assays in which micronuclei and dicentrics are assessed in the same cell dishes (10,11) and the analysis of induction of DNA damage foci taking into account the influence of the irradiation geometry (e.g. ...
Article
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.
... This was later demonstrated to imply the one-to-one correspondence between the probability of two or more ionizations to apply only approximately and only for low-LET radiation Rabus and Nettelbeck 2011). Conte et al. (2017Conte et al. ( , 2018 and Selva et al. (2019) demonstrated that a link between nanodosimetry and cell survival can be based on cumulative probabilities of ionization ...
... The solid lines are Poisson distributions of the same average as the data represented by symbols. For details see text a role Rabus and Nettelbeck 2011;Conte et al. 2017Conte et al. , 2018Selva et al. 2019). ...
Article
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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.
... In addition, we quantified the ionization detail (ID) (Ramos-Méndez et al 2018a) through clusters size distributions in a biologically relevant volume by means of the nanodosimetric quantities: first moment (M 1 ) and the cumulative probability of having ionization clusters of size larger or equal than two (F 2 ) (Rollet et al 2010). Both quantities have been shown to correlate with inactivation cross-section of cells in (Conte et al 2017a(Conte et al , 2017b. Finally, we estimated the direct damage to the DNA through the number of double-strand breaks (DSBs) caused by the decay of 64 Cu using the clustering algorithm DBSCAN (Ester et al 1996). ...
... In 1992, it was shown that the clusters of multiple ionizations produced by ionizing radiation in spherical volumes of 2 to 3 nm diameter correlate well with the formation of DSBs (Brenner and Ward 1992). Lately, P ν and nanodosimetric quantities M 1 and F 2 have been shown to correlate with DSBs and cell survival (Garty et al 2010, Conte et al 2017a, 2017b. Hence, we used a cylindrical volume of liquid water of 2.3 nm in diameter and 3.4 nm in length (corresponding to a DNA segment of 10 base-pairs in length) to calculate P ν (T) with TOPAS-nBio. ...
Article
TOPAS-nBio was used to simulate, collision-to-collision, the complete trajectories of electrons in water generated during the explicit simulation of 64Cu decay. S-values and direct damage to the DNA were calculated representing the cell (C) and the cell nucleus (N) with concentric spheres of 5 μm and 4 μm in radius, respectively. The considered "target"←"source" configurations, including the cell surface (Cs) and cytoplasm (Cy), were: C←C, C←Cs, N←N, N←Cy and N←Cs. Ionization cluster size distributions were also calculated in a cylinder immersed in water corresponding to a DNA segment of 10 base-pairs in length (diameter 2.3 nm, length 3.4 nm), modeling a radioactive point source moving from the central axis to the edge of the cylinder. For that, the first moment (M1) and cumulative probability of having a cluster size of 2 or more ionizations in the cylindrical volume (F2) were obtained. Finally, the direct damage to the DNA was estimated by quantifying double-strand breaks (DSBs) using the clustering algorithm DBSCAN. The S-values obtained with TOPAS-nBio for 64Cu were 7.879x10-4±5x10-7, 4.351x10-4±6x10-7, 1.442x10-3±1x10-6, 2.596x10-4±8x10-7, 1.127x10-4±4x10-7 Gy/Bq-s for the configurations C←C, C←Cs, N←N, N←Cy and N←Cs, respectively. The difference of these values, compared with previously reported S-values for 64Cu with the code MNCP and software MIRDCell, ranged from -4% to -25% for the configurations N←N and N←Cs, respectively. On the other hand, F2 was maximum with the source at the center of the cylinder 0.373±0.001, and monotonically decreased until reaching a value of 0.058±0.001 at 2.3 nm. The same behavior was observed for M1 with values ranging from 2.188±0.004 to 0.242±0.002. Finally, the DBSCAN algorithm showed that the mean number of DNA DSBs per decay were 0.187±0.001, 0.0317±0.0005, and 0.0125±0.0002 DSB-(Bq-s)-1 for the configurations N←N, N←Cs, and N←Cy, respectively. In conclusion, the results of the S-values show that the absorbed dose strongly depends on the distribution of the radionuclide in the cell, the dose being higher when 64Cu is internalized in the cell nucleus, which is reinforced by the nanodosimetric study by the presence of DNA DSBs attributable to the Auger electrons emitted during the decay of 64Cu.
... all of these detectors, except the FIRE detector, are large-sized and not portable. Additionally, some discrepancies between experimentally obtained cluster size distributions with the different detectors exist [17,18]. However, a comparison of cluster sizes obtained by different detectors is difficult since they measure the number of ionizations in different volume sizes. ...
... However, a comparison of cluster sizes obtained by different detectors is difficult since they measure the number of ionizations in different volume sizes. Nevertheless, it has been shown that the cumulative probabilities 1 , 2 and 3 as a function of the first moment 1 are independent of detector type, volume size and radiation quality [18]. ...
Article
Full-text available
One goal of nanodosimetry is to determine statistical quantities of ionization distributions in nanometric volumes. It is hypothesized here that these quantities are related to the initial biological damages in the DNA from ionizations. Thus nanodosimetric quantities will potentially complement or replace the concept of RBE-weighted absorbed dose and hence they could be applied in treatment planning systems, risk assessments for radiation protection and space radiation. Thus the development of a compact and portable nanodosimeter detector available for clinical routine is a significant step towards that goal.We present extensive measurements to characterize the performance of the FIRE (Frequency of Ion REgistration) nanodosimeter detector. It operates on similar principles like the Gas Electron Multiplier (GEM). Contrary to GEMs the FIRE detector registers positive ions instead of electrons and operates at low pressures of 0.5 Torr to 2.5 Torr. In addition, the FIRE nanodosimeter capitalizes on the usage of a resistive cathode in order to suppress discharges. Moreover, the geometry of the FIRE detector is adapted to the low pressure by enlarging the typical dimensions of a GEM foil by two orders of magnitude. The authors present two configurations of the compact FIRE nanodosimetry detector. The resistivities of the two configurations differ by six orders of magnitude. The lower resistivity should allow for faster removal of the charges attached to the wall inside the hole channel. Measurements of mean number of ions produced by 5MeV alpha particles in low pressure propane gas, mean number of dark counts, the ion arrival time, and the mean avalanche charge are presented. The dependency of these parameters on acceleration voltage, drift voltage, pressure and hole diameter were investigated.
... On the other hand, the pattern of particle interactions at the nanometer level is measured by track-nanodosimetry, which assesses the single-event distribution of ionization cluster size for site dimensions from a few nanometers up to tens of nanometers. Nanodosimetric probability distributions have de- monstrated to show a trend similar to the cellular inactivation cross- sections ( Conte et al., 2015Conte et al., , 2017aConte et al., , 2017b). Anyway, only three detectors are available worldwide (De Nardo et al., 2002;Garty et al., 2002;Pszona and Gajewski, 1994) and they cannot be transported ea- sily to different irradiation facilities. ...
Article
The lower operation limit of common tissue equivalent proportional counters (TEPCs) is about 0.3 μm in simulated site. On the other hand, the pattern of the particle interactions at the nanometric level, which has a correlation with the radiation induced damage on the DNA, is measurable by only three instruments worldwide. In order to fill this gap, a novel TEPC capable of simulating site sizes down to 25 nm was designed and constructed. Its response was characterized with gamma, neutron and carbon beams and the capability in measuring microdosimetric spectra at 25 nm was demonstrated. The present paper aims at describing a further characterization of this TEPC by simulating with the Monte Carlo FLUKA code the microdosimetric spectra measured with a carbon beam. Since the sensitive volume of the TEPC has an unconventional shape, a study on the chord length distribution for the adopted irradiation set-up was performed and compared with the analytical one. The results show a good agreement between the experimental data and the FLUKA simulations, showing that this code is capable of reproducing microdosimetric spectra of a carbon beam down to 25 nm in simulated site.
... A correction of the simulation results with respect to the inclusion of the secondary ion production is sufficient for a mere comparison of the simulated with measured cluster size distributions. However, for the prediction of the biological effectiveness of different radiation qualities [6,7], the "true" cluster size distributions must be determined. A procedure therefore needs to be applied to the measured data to remove the effects of the background due to secondary ionisations. ...
Article
Full-text available
Nanodosimetry is a methodology for quantifying the effects of ionising radiation on matter by determining the frequency distributions of the cluster size of ionisations in nanometric target volumes. In previous investigations with the Ion Counter nanodosimeter operated at PTB, 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 by a background of secondary ions, which are produced within the transport system of the ionised target molecules. In this paper, two different approaches were investigated to correct for the background of secondary ions in the measured data to obtain the "true" cluster size distribution to be used, e. g., in predictions of biological effectiveness. In the first approach, the correction of the background was treated as a minimising problem. In the second approach, an iterative unfolding algorithm using Bayes statistics was employed. In all cases where the convolution of the background-corrected results with the secondary ion background agrees well with the corresponding measured cluster size distribution, the background-correction led to an improved agreement between measurement and simulation. For the removal of a background of secondary ions from measured cluster size distributions, the unfolding algorithm using Bayes statistics is the preferred method as it proved to be the most effective and the least sensitive to boundary conditions. Moreover, it was considerably less time consuming.
... In experimental nanodosimetry, some particular characteristics of the track structure, namely the cumulative probabilities F 1 , F 2 and F 3 of measuring at least 1, 2 or 3 ionizations in the target volume, are almost uniquely determined by the mean cluster size of the ionization cluster size distribution, independent of its particular shape (Conte et al., 2017). This experimental investigation aims at establishing a new concept of radiation quality that builds on measurable characteristics of the particle track structure at the nanometer scale. ...
Article
In this review, the multiscale approach in radiation dosimetry in relation to biological effects is first briefly introduced. The need of dosimetry in microscopic regions, for example in cells, is then addressed, followed by a review of the basic microdosimetric quantities of internal emitters. The requirement of understanding the molecular biological effects of radiation leads to the dosimetric concept in the nanometer ranges, where the initial events produced at the molecular level cause the subsequent cellular and tissue effects that may lead to cancer. Track structure theory is particularly introduced in nanodosimetry for internal emitters. The relationship between the quantities in macroscopic dosimetry, e.g. absorbed dose, the microdosimetric quantities, e.g. specific energy and lineal energy, and the nanodosimetric characteristics, the track structures is inherently established in a derivational way. The significance of microdosimetric and nanodosimetric quantities in understanding and interpreting the mechanisms of radiobiological effects is addressed. Several applications of microdosimetry and nanodosimetry for internal emitters in radon and thoron progeny dosimetry and risk analysis, in targeted radionuclide therapy, in modelling of DNA damages and as a tool in the potential interpretation of dose-response relationship at low doses and dose rates are given. Finally, the potential future development of internal microdosimetry and nanodosimetry is outlined.
... In a subsequent work by Conte et al., these finding were exploited even further to establish a link between measured nanodosimetric parameters of ion track structure and the coefficients of the linear-quadratic model for cell survival [19]. This progress has stimulated investigations into the potential use of nanodosimetric parameters in treatment planning, as these offer the advantage of measurable quantities linked to the biological outcome of the irradiation [20], [21], [22]. ...
Preprint
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.
... Until now, about 160 colleagues downloaded the previous version PIDE 2.0 and about 100 the current version PIDE 3.2. The database has been used within a considerable number of publications so far for different purposes in the fields of radiation biology and therapy in our own group [5][6][7][8] as well as from others [9][10][11][12][13][14][15][16][17][18][19]. Also, colleagues reported to us that they used the database to identify available data they found useful for their research, and to become aware of degrees of freedom impacting radiation response. ...
Article
Full-text available
The particle irradiation data ensemble (PIDE) is the largest database of cell survival data measured after exposure to ion beams and photon reference radiation. We report here on the updated version of the PIDE database and demonstrate how to investigate generic properties of radiation dose response using these sets of raw data. The database now contains information of over 1100 pairs of photon and ion dose response curves. It provides the originally published raw data of cell survival in addition to given linear quadratic (LQ) model parameters. If available, the raw data were used to derive LQ model parameters in the same way for all experiments. To demonstrate the extent of the database and the variability among experiments we focus on the dose response curves after ion and photon radiation separately in a first step. Furthermore, we discuss the capability and the limitations of the database for analyzing properties of low and high linear energy transfer (LET) radiation response based on multiple experiments. PIDE is freely available to the research community under www.gsi.de/bio-pide.
Article
It is recognized today that the observable radiobiological effects of ionizing radiations are strongly correlated to the local density of lesions produced in micrometer- and nanometer-sized subcellular structures, and thus to the track structure properties of interacting particles. In view of the emerging interest of carbon ions in radiotherapy, an experimental study was done for characterizing the track structure of carbon ions at different energies close to the Bragg peak. Ionization cluster size distributions for nanometer-sized target volumes were measured with the Startrack-Counter installed at the TANDEM-ALPI accelerator complex at LNL, and calculated by means of a dedicated Monte Carlo code. Measurements and simulations were performed for particle tracks crossing directly the target volume or passing nearby at specified impact parameters. Results will be presented and discussed for ¹²C-ions at 6, 8, 12.5 and 20 MeV per nucleon.
Article
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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.
Article
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.
Article
Experimental nanodosimetry aims to develop a new concept of radiation quality, based on the correlation between initial features of particle tracks and late biological outcome. A direct proportionality has been observed between the cumulative probability of measuring at least k ionisations within a nanometric volume and inactivation cross sections at specific survival levels. Based on this proportionality, physical quantities which are measurable at the nanometre level can be used to estimate the alpha and beta parameters of the linear-quadratic dose-response model, provided that two proportionality factors are determined in a reference radiation field. This work describes the procedure and first results applied to published data for V79 cell survival after irradiation with protons and carbon ions.
Article
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The tissue equivalent proportional counter (TEPC) is the most accurate device for measuring the microdosimetric properties of a particle beam, nevertheless no detailed information on the track structure of the impinging particles can be obtained, since the lower operation limit of common TEPCs is about 0.3 μm. On the other hand, the pattern of particle interactions is measured by track-nanodosimetry, which derives the single-event distribution of ionization cluster size at the nanometric scale. Anyway, only three nanodosimeters are available worldwide. A feasibility study for extending the performances of TEPC down to the nanometric region was performed and a novel avalanche-confinement TEPC was designed and constructed. This detector is constituted by a cylindrical chamber, based on a three-electrode structure, connected to a vacuum and gas flow system to ensure a continuous replacement of the tissue equivalent gas, thus allowing to simulate different biological site sizes in the range 300-25 nm. This TEPC can be calibrated by exploiting a built-in alpha source and a miniaturized solid-state detector as a trigger. Irradiations with photons, fast neutrons and two hadron beams demonstrated the good performances of the device. A satisfactory agreement with FLUKA simulations was obtained.
Article
An attempt towards an experimental set up which could provide the experimental data on correlation processes occurred simultaneously in two distanced DNA targets within a charged particle track is presented. A modified Jet Counter nanodosemeter was used in two experiments with carbon ions with mean energies of 52 and 23 MeV. The probability distributions of the correlated pairs of ionisation clusters produced in two neighbouring sensitive volumes are presented. A question of potential new descriptors of radiation quality is raised.
Article
The production of two double strand breaks in spatially separated locations on the DNA molecule can cause the loss of a whole DNA loop. This loss, which can be of substantial length depending on the geometrical position of the two damaged sites, depends on the degree of correlation between ionisation clusters formed in sites of several nanometres in size. The first part of this paper reported on 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. 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 PTra, a track structure code 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 experiment were found to be in good agreement with the measurements for the investigated irradiation geometries.
Article
TOPAS-nBio was used to simulate, collision-to-collision, the complete trajectories of electrons in water generated during the explicit simulation of 64Cu decay. S-values and direct damage to the DNA were calculated representing the cell (C) and the cell nucleus (N) with concentric spheres of 5 μm and 4 μm in radius, respectively. The considered "target"←"source" configurations, including the cell surface (Cs) and cytoplasm (Cy), were: C←C, C←Cs, N←N, N←Cy and N←Cs. Ionization cluster size distributions were also calculated in a cylinder immersed in water corresponding to a DNA segment of 10 base-pairs in length (diameter 2.3 nm, length 3.4 nm), modeling a radioactive point source moving from the central axis to the edge of the cylinder. For that, the first moment (M1) and cumulative probability of having a cluster size of 2 or more ionizations in the cylindrical volume (F2) were obtained. Finally, the direct damage to the DNA was estimated by quantifying double-strand breaks (DSBs) using the clustering algorithm DBSCAN. The S-values obtained with TOPAS-nBio for 64Cu were 7.879x10-4±5x10-7, 4.351x10-4±6x10-7, 1.442x10-3±1x10-6, 2.596x10-4±8x10-7, 1.127x10-4±4x10-7 Gy/Bq-s for the configurations C←C, C←Cs, N←N, N←Cy and N←Cs, respectively. The difference of these values, compared with previously reported S-values for 64Cu with the code MNCP and software MIRDCell, ranged from -4% to -25% for the configurations N←N and N←Cs, respectively. On the other hand, F2 was maximum with the source at the center of the cylinder 0.373±0.001, and monotonically decreased until reaching a value of 0.058±0.001 at 2.3 nm. The same behavior was observed for M1 with values ranging from 2.188±0.004 to 0.242±0.002. Finally, the DBSCAN algorithm showed that the mean number of DNA DSBs per decay were 0.187±0.001, 0.0317±0.0005, and 0.0125±0.0002 DSB-(Bq-s)-1 for the configurations N←N, N←Cs, and N←Cy, respectively. In conclusion, the results of the S-values show that the absorbed dose strongly depends on the distribution of the radionuclide in the cell, the dose being higher when 64Cu is internalized in the cell nucleus, which is reinforced by the nanodosimetric study by the presence of DNA DSBs attributable to the Auger electrons emitted during the decay of 64Cu.
Article
Full-text available
Energetic carbon ions are promising projectiles used for cancer radiotherapy. A thorough knowledge of how the energy of these ions is deposited in biological media (mainly composed of liquid water) is required. This can be attained by means of detailed computer simulations, both macroscopically (relevant for appropriately delivering the dose) and at the nanoscale (important for determining the inflicted radiobiological damage). The energy lost per unit path length (i.e., the so-called stopping power) of carbon ions is here theoretically calculated within the dielectric formalism from the excitation spectrum of liquid water obtained from two complementary approaches (one relying on an optical-data model and the other exclusively on ab initio calculations). In addition, the energy carried at the nanometre scale by the generated secondary electrons around the ion’s path is simulated by means of a detailed Monte Carlo code. For this purpose, we use the ion and electron cross sections calculated by means of state-of-the art approaches suited to take into account the condensed-phase nature of the liquid water target. As a result of these simulations, the radial dose around the ion’s path is obtained, as well as the distributions of clustered events in nanometric volumes similar to the dimensions of DNA convolutions, contributing to the biological damage for carbon ions in a wide energy range, covering from the plateau to the maximum of the Bragg peak.
Preprint
The effective use of swift ion beams in cancer treatment (known as hadrontherapy) as well as an appropriate protection in manned space missions rely on the accurate understanding of energy delivery to cells damaging their genetic information. The key ingredient characterizing the response of a medium to the perturbation induced by charged particles is its electronic excitation spectrum. By using linear response time-dependent density functional theory, we obtain the energy and momentum transfer excitation spectrum (the energy-loss function, ELF) of liquid water (main constituent of biological tissues), in excellent agreement with experimental data. The inelastic scattering cross sections obtained from this ELF, together with the elastic scattering cross sections derived considering the condensed phase nature of the medium, are used to perform accurate Monte Carlo simulations of the energy deposited by swift carbon ions in liquid water and carried away by the generated secondary electrons producing inelastic events (ionization, excitation, and dissociation electron attachment, DEA), strongly correlated with cellular death, which are scored in sensitive volumes having the size of two DNA convolutions. The sizes of clusters of damaging events for a wide range of carbon ion energies, from those relevant to hadrontherapy up to cosmic radiation, predict with unprecedented statistical accuracy the nature and relative magnitude of the main inelastic processes contributing to radiation biodamage, confirming that ionization accounts for the vast majority of complex damage. DEA, typically regarded as a very relevant biodamage mechanism, surprisingly plays a minor role in carbon-ion induced clusters of harmful events.
Conference Paper
It is recognized today that the observable radiobiological effects of ionizing radiations are strongly correlated to the clustering of damages in micrometer-and nanometer-sized subcellular structures, hence to the particle track structure. The characteristic properties of track structure are directly measurable nowadays with bulky experimental apparatuses, which cannot be easily operated in a clinical environment. It is therefore interesting to investigate the feasibility of new portable detectors able to characterize the real therapeutic beams. With this in mind, a novel avalanche-confinement Tissue Equivalent Proportional Counter (TEPC) was constructed for simulating nanometric sites down to 25 nm. Experimental cluster size distributions measured with this TEPC were compared with Monte Carlo simulations of the same experiment and with cluster size distributions measured with the Startrack nanodosimeter.
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The purpose of this study is to investigate and quantify the influence of nanoparticle composition, size, and concentration on the difference between dose enhancement values derived from Monte Carlo simulations with homogeneous and structured geometrical representations of the target region in metal nanoparticle-enhanced photon brachytherapy. Values of the dose enhancement factor (DEF) were calculated for Pd-103, I-125, and Cs-131 brachytherapy sources with gold, silver, or platinum nanoparticles acting as targeting agents. Simulations were performed using the Geant4 toolkit with condensed history models of electron transport. Stringent limits were imposed on adjustable parameters that define secondary electron histories, so that simulations came closest to true event-by-event electron tracking, thereby allowing part of the nanoparticle-laden volume used for calculating the dose to be represented as a structured region with uniformly distributed discrete nanoparticles. Fine-tuned physical models of secondary radiation emission and propagation, along with the discrete geometrical representation of nanoparticles, result in a more realistic assessment of dose enhancement. The DEF correction coefficient is introduced as a metric that quantifies the absorption of secondary radiation inside the nanoparticles themselves, a phenomenon disregarded when the target region is treated as a homogeneous metal–tissue mixture, but accounted for by discrete nanoparticle representation. The approach applied to correcting DEF values both draws from and expands upon several related investigations published previously. Comparison of the obtained results to those found in relevant references shows both agreement and deviation, depending on nanoparticle properties and photon energy.
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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).
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The radiobiological effects of ionising radiations are strongly correlated to the local density of lesions produced in micrometre- and nanometre-sized subcellular structures, and thus to the track structure properties of interacting particles. These properties have been studied mainly by means of Monte Carlo simulations, however experimental methodologies and instruments have also been developed that allow to measure the stochastics of ionisations produced in a nanometric sensitive volume (SV) by charged particles crossing it or passing nearby at specified distances. The number ν of ionisations produced in SV by the passage of a single primary ionising particle is measured, and the measurement is repeated many times to produce a probability distribution P(ν), called ionisation cluster size distribution. Measurable quantities can be derived that correlate with the biological effectiveness of the specific radiation quality (ion type and velocity). In view of the emerging interest of carbon ions in radiotherapy, it is important to characterize not only the track structure of carbon ions but also that of other light ions that are produced in nuclear interactions. This work presents first experimental results for boron ions at 80 MeV. Ionisation cluster size distributions were measured with the Startrack-Counter installed at the TANDEM-ALPI accelerator complex at the Legnaro National Laboratories (LNL) of the Italian Istituto Nazionale di Fisica Nucleare (INFN) and simulated by means of a dedicated Monte Carlo code. Measurements and simulations were performed for particles that traverse directly the sensitive volume or pass nearby at specified impact parameters.
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This topical review summarizes underlying concepts of nanodosimetry. It describes the development and current status of nanodosimetric detector technology. It also gives an overview of Monte Carlo track structure simulations that can provide nanodosimetric parameters for treatment planning of proton and ion therapy. Classical and modern radiobiological assays that can be used to demonstrate the relationship between the frequency and complexity of DNA lesion clusters and nanodosimetric parameters are reviewed. At the end of the review, existing approaches of treatment planning based on RBE models or dose-averaged linear energy transfer are contrasted with an RBE-independent approach based on nandosimetric parameters. Beyond treatment planning, nanodosimetry is also expected to have applications and give new insights into radiation protection dosimetry.
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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.
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In radiation physics, the biological effectiveness of radiation is generally estimated from the energy imparted to a sensitive volume of given size. However, measurements of this quantity are carried out almost exclusively with ionization-based techniques, by converting the ionization charge signal to energy imparted by means of a constant calibration factor, independent of particle type and energy. This procedure is reliable when the tissue-equivalent size of the sensitive volume is of the order of 1 μm and larger, since in this case the number of radiation-induced collisions is high and the distribution of energy transfers per single collision is masked by the multiple averaging. However, its reliability can be called into question when the size of the sensitive volume is decreased to the nanometre scale, as it is the case in experimental nanodosimetry. For this reason, the present study investigates the relationship between the two stochastic quantities energy imparted and ionization yield, calculated by Monte Carlo simulations in spherical sensitive volumes with diameter ranging from 100 nm down to 1 nm. The analysis was carried out for protons and carbon ions in the energy range from 1 to 100 MeV/u, crossing liquid-water sensitive spheres along their diameter. Simulations were done by means of the Geant4-DNA Monte Carlo code, with two different physics lists. A strong correlation between the energy imparted and the ionization yield was found, which comprises not only their mean values, but their entire stochastic distributions, even when the diameter of the sensitive volume is as small as 1 nm.
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The measurable radiobiological effects of ionizing radiation strongly depend on the clustering of damages in subcellular sites, which are related to the particles track structure. The characteristic properties of track structure are directly measurable nowadays with bulky experimental apparatuses, which are not easily transportable and are not suited for the clinical environment. For this reason, the feasibility of new transportable detectors capable of characterizing real therapeutic beams was investigated in recent years. In particular, two novel avalanche-confinement Tissue Equivalent Proportional Counters (TEPCs) were designed and constructed for simulating nanometric sites down to 25 nm: a sealed version for operation in plain air and a new prototype with perforated walls and without external encapsulating cap for operation in a vacuum chamber with accelerated particle beams. This work is focused on the response of the open TEPC, directly installed in the vacuum chamber of the STARTRACK nanodosimeter of the Italian Istituto Nazionale di Fisica Nucleare – Laboratori Nazionali di Legnaro (INFN-LNL), against He-4 particles from a ²⁴⁴Cm isotopic source and 26.7 MeV Li-7 ions accelerated by the Tandem accelerator of LNL. Experimental cluster size distributions of He-4 and Li-7 ions measured with this TEPC are compared with nanodosimetric Monte Carlo simulations and with cluster size distributions measured with the STRATRACK nanodosimeter. Both comparisons highlight a very good agreement: the relative variance added by the electron multiplication process results negligible if compared to the variability of the ionization process. This encourages the use of the avalanche-confinement TEPC as a portable detector for nanodosimetric characterization of particle tracks.
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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.
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To study the track structure of light ions, a measuring device has been developed at the Legnaro National Laboratory of INFN, which can be used to investigate separately the penumbra region of particle tracks and the track-core region, which is a few nanometres in diameter. The device is based on single-electron counting techniques by means of a gas detector; it simulates a 'nanometre-sized' biological volume of about 20 nm in diameter that can be moved with respect to a narrow particle beam to measure the ionization-cluster-size distributions caused within the target volume by the passage of single primary particles, as a function of the impact parameter. To investigate the ionization-cluster-size formation caused by primary particles of medical interest when they penetrate through or pass by the target volume at a specified impact parameter, measurements and Monte Carlo simulations were performed for 20 MeV protons, 16 MeV deuterons, 48 MeV 6Li-ions, 26.7 MeV 7Li-ions and 96 MeV 12C-ions. The detailed analysis of the resulting distributions showed that in the track-core region their shape is mainly determined by the mean free ionization path length of the primary particles, whereas in the penumbra region the shape of the distributions is almost independent of the impact parameter, and also of the particle type and velocity.
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DNA damage of exposed tumour tissue leading to cell death is one of the detrimental effects of ionising radiation that is exploited, with beneficial consequences, for radiotherapy. The pattern of the discrete energy depositions during passage of the ionising track of radiation defines the spatial distribution of lesions induced in DNA with a fraction of the DNA damage sites containing clusters of lesions, formed over a few nanometres, against a background of endogenously induced individual lesions. These clustered DNA damage sites, which may be considered as a signature of ionising radiation, underlie the deleterious biological consequences of ionising radiation. The concepts developed rely in part on the fact that ionising radiation creates significant levels of clustered DNA damage, including complex double-strand breaks (DSB), to kill tumour cells as clustered damage sites are difficult to repair. This reduced repairability of clustered DNA damage using specific repair pathways is exploitable in radiotherapy for the treatment of cancer. We discuss some potential strategies to enhance radiosensitivity by targeting the repair pathways of radiation-induced clustered damage and complex DNA DSB, through inhibition of specific proteins that are not required in the repair pathways for endogenous damage. The variety and severity of DNA damage from ionising radiation is also influenced by the tumour microenvironment, being especially sensitive to the oxygen status of the cells. For instance, nitric oxide is known to influence the types of damage induced by radiation under hypoxic conditions. A potential strategy based on bioreductive activation of pro-drugs to release nitric oxide is discussed as an approach to deliver nitric oxide to hypoxic tumours during radiotherapy. The ultimate aim of this review is to stimulate thinking on how knowledge of the complexity of radiation-induced DNA damage may contribute to the development of adjuncts to radiotherapy.
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For tumor therapy with light ions and for experimental aspects in particle radiobiology the relative biological effectiveness (RBE) is an important quantity to describe the increased effectiveness of particle radiation. By establishing and analysing a database of ion and photon cell survival data, some remarkable properties of RBE-related quantities were observed. The database consists of 855 in vitro cell survival experiments after ion and photon irradiation. The experiments comprise curves obtained in different labs, using different ion species, different irradiation modalities, the whole range of accessible energies and linear energy transfers (LETs) and various cell types. Each survival curve has been parameterized using the linear-quadratic (LQ) model. The photon parameters, α and β, appear to be slightly anti-correlated, which might point toward an underlying biological mechanism. The RBE values derived from the survival curves support the known dependence of RBE on LET, on particle species and dose. A positive correlation of RBE with the ratio α/β of the photon LQ parameters is found at low doses, which unexpectedly changes to a negative correlation at high doses. Furthermore, we investigated the course of the β coefficient of the LQ model with increasing LET, finding typically a slight initial increase and a final falloff to zero. The observed fluctuations in RBE values of comparable experiments resemble overall RBE uncertainties, which is of relevance for treatment planning. The database can also be used for extensive testing of RBE models. We thus compare simulations with the local effect model to achieve this goal.
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This work aimed at measuring cell-killing effectiveness of monoenergetic and Spread-Out Bragg Peak (SOBP) carbon-ion beams in normal and tumour cells with different radiation sensitivity. Clonogenic survival was assayed in normal and tumour human cell lines exhibiting different radiosensitivity to X- or gamma-rays following exposure to monoenergetic carbon-ion beams (incident LET 13-303 keV/microm) and at various positions along the ionization curve of a therapeutic carbon-ion beam, corresponding to three dose-averaged LET (LET(d)) values (40, 50 and 75 keV/microm). Chinese hamster V79 cells were also used. Carbon-ion effectiveness for cell inactivation generally increased with LET for monoenergetic beams, with the largest gain in cell-killing obtained in the cells most radioresistant to X- or gamma-rays. Such an increased effectiveness in cells less responsive to low LET radiation was found also for SOBP irradiation, but the latter was less effective compared with monoenergetic ion beams of the same LET. Our data show the superior effectiveness for cell-killing exhibited by carbon-ion beams compared to lower LET radiation, particularly in tumour cells radioresistant to X- or gamma-rays, hence the advantage of using such beams in radiotherapy. The observed lower effectiveness of SOBP irradiation compared to monoenergetic carbon beam irradiation argues against the radiobiological equivalence between dose-averaged LET in a point in the SOBP and the corresponding monoenergetic beams.
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A wall-less ion-counting nanodosemeter, conceived for precise ionisation-cluster measurements in an accelerator environment, is described. The technique provides an accurate means for counting single radiation-induced ions, in dilute gas models of condensed matter. The sensitive volume dimensions, a few tissue-equivalent nm in diameter by a few tens of nm, are tunable by a proper choice of the gas pressure and electric fields: nanometric sub-sections can be electronically selected. Detailed ion-cluster distributions are presented for protons of 7.15, 13.6 and 19.3 MeV, in biologically relevant DNA-like sensitive volumes of low-pressure propane. Experimental results are compared to model simulations.
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The paper presents data for measured ionization cluster size distributions by alpha particles in tissue equivalent media and comparison with the simulated data for liquid water. The experiments were carried out with a beam of 4.6 MeV alpha particles performed in a setup called the JET Counter. The theoretically derived cluster size distributions for alphas particles were obtained using the K-means algorithm. The simulation was carried out by Monte Carlo track structure calculations using cross sections for liquid water. The first moments of cluster size distributions, derived from K-means algorithm as a function of diameter of cluster centroid, were compared with the corresponding moments derived from the experiments for nitrogen and propane targets. It was found that the ratio of the first moments for water to gas targets correlates well with the corresponding ratio of the mean free paths for primary ionization by alpha particles in the two media. It is shown that the cluster size distributions for alpha particles in water, obtained from K-means algorithm, are in agreement with the corresponding distributions measured experimentally in nitrogen or propane gas targets of nanometer sizes.
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Proton therapy treatments are based on a proton RBE (relative biological effectiveness) relative to high-energy photons of 1.1. The use of this generic, spatially invariant RBE within tumors and normal tissues disregards the evidence that proton RBE varies with linear energy transfer (LET), physiological and biological factors, and clinical endpoint. Based on the available experimental data from published literature, this review analyzes relationships of RBE with dose, biological endpoint and physical properties of proton beams. The review distinguishes between endpoints relevant for tumor control probability and those potentially relevant for normal tissue complication. Numerous endpoints and experiments on sub-cellular damage and repair effects are discussed. Despite the large amount of data, considerable uncertainties in proton RBE values remain. As an average RBE for cell survival in the center of a typical spread-out Bragg peak (SOBP), the data support a value of ~1.15 at 2 Gy/fraction. The proton RBE increases with increasing LETd and thus with depth in an SOBP from ~1.1 in the entrance region, to ~1.15 in the center, ~1.35 at the distal edge and ~1.7 in the distal fall-off (when averaged over all cell lines, which may not be clinically representative). For small modulation widths the values could be increased. Furthermore, there is a trend of an increase in RBE as (α/β)x decreases. In most cases the RBE also increases with decreasing dose, specifically for systems with low (α/β)x. Data on RBE for endpoints other than clonogenic cell survival are too diverse to allow general statements other than that the RBE is, on average, in line with a value of ~1.1. This review can serve as a source for defining input parameters for applying or refining biophysical models and to identify endpoints where additional radiobiological data are needed in order to reduce the uncertainties to clinically acceptable levels.
Article
The track nanodosemeter developed at the National Laboratories of Legnaro (LNL), Italy allows the direct investigation of the properties of particle tracks, by measuring ionisation-cluster-size distributions caused by ionising particles within a ‘nanometre-sized’ target volume while passing it at a well-specified impact parameter. To supplement the measurements, a dedicated Monte Carlo code was developed which is able to reproduce the general shape of measured cluster-size distributions with a satisfactory quality. To reduce the still existing quantitative differences between measured and simulated data, the validity of cross sections used in the Monte Carlo model was revisited again, taking into account the large amount of data available now from recent track structure measurements at LNL. Here, special emphasis was laid on a deeper and detailed investigation of the cross sections applied to calculate the energy of secondary electrons after impact ionisation of primary particles: the cross sections due to the HKS model and the so-called Rudd model. Representative results for 240 MeV 12C-ions are presented.
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A new method is presented for measuring the frequency distribution of ion clusters, formed in nanometre sections of track, by charged particles. The simulated nanometer-size sites are produced in a device, called the Jet Counter. It consists of a pulse-operated valve which injects an expanding jet of nitrogen gas into an interaction chamber. The resulting distributions of ion clusters produced by alpha particle tracks (from 241Am) in sections ranging from 2 to around 10nm at unit density in nitrogen gas have been measured. Analysis of the experimental results confirm that the primary ionisation distributions produced in the nanometer sections comply with the Poisson distribution. The ionisation cluster distributions produced in the 2–10nm track-segments are the first ever to be determined experimentally.
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Auger-electron-emitting radionuclides (for instance, 125I) with a predominant energy spectrum below 3 keV are an active area of research towards the clinical application of radiopharmaceuticals. Hence, the necessity for an adequate description of the effects of radiation by low-energy electrons on nanometric biological targets seems to be unquestionable. Experimental nanodosimetry for low-energy electrons has been accomplished with a device named JET COUNTER. The present paper describes, for the first time, nanodosimetric experiments in nanometer-sized cavities of nitrogen using low energy electrons ranging from 100 eV to 2 keV.
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The LET position of the RBE maximum and its dependence on the cellular repair capacity was determined for carbon ions. Hamster cell lines of differing repair capacity were irradiated with monoenergetic carbon ions. RBE values for cell inactivation at different survival levels were determined and the differences in the RBE-LET patterns were compared with the individual sensitivity to photon irradiation of the different cell lines. Three hamster cell lines, the wild-type cell lines V79 and CHO-K1 and the radiosensitive CHO mutant xrs5, were irradiated with carbon ions of different energies (2.4-266.4 MeV/u) and LET values (13.7-482.7 keV/microm) and inactivation data were measured in comparison to 250 kV x-rays. For the repair-proficient cell lines a RBE maximum was found at LET values between 150 and 200 keV/microm. For the repair-deficient cell line the RBE failed to show a maximum and decreased continuously for LET values above 100 keV/microm. The carbon RBE LET relationship for inactivation is shifted to higher LET values compared with protons and alpha-particles. RBE correlated with the repair capacity of the cells.