Objectives: The main aim of this study consists of testing the consistency and reliability of the BIANCA (BIophysical ANalysis of Cell death and chromosome Aberrations) biophysical model across different radiation transport codes in the framework of cancer ion-therapy research. Methods: Spread-Out Bragg Peak (SOBP) profiles for protons, helium ions and carbon ions were simulated at three different depth ranges (2-3 cm, 5-8 cm, and 10-15 cm) applying two radiation transport codes, FLUKA and Geant4. While BIANCA has been interfaced to FLUKA in a previous work, an interface with Geant4 was purposely developed in this work. Cell survival along all considered SOBP profiles was predicted by BIANCA for two cell lines with very different radiosensitivities: Squamous Cell Carcinoma (SCC), with α/β = 12.68 Gy, and chordoma, with α/β = 2.37 Gy. The agreement between the predictions obtained from the two approaches was quantitatively evaluated by means of Root Mean Square Error (RMSE) and Gamma Index analysis, both for physical dose distributions and for cell survival predictions. Results: The comparison between FLUKA and Geant4 simulations demonstrated good agreement. The Gamma Index analysis yielded passing rates exceeding 94.9% for physical dose profiles (criteria: 3%/2 mm) and 96.0% for cell survival probabilities (criteria: 2%/2 mm) across all considered ion species (protons, He, C) and depths. Root Mean Square Error (RMSE) analysis confirmed average discrepancies below 2.5% for physical dose and 1% for biological survival. Conclusions: This study shows that the BIANCA model can be applied to predict cell killing along hadron therapy beams when interfaced both with FLUKA and with Geant4. Furthermore, the successful implementation of the interface with Geant4 expands the accessibility and applicability of BIANCA, paving the way for its future integration into different transport codes and/or treatment planning systems.

According to NASA's plans, a human travel to the Moon is planned by the end of 2025 with the Artemis II mission, and humans should land on the Moon again in 2026. Exposure to space radiation is one of the main risks for the crew members; while for these short missions the doses from galactic cosmic rays would be relatively low, the possible occurrence of an intense solar particle event (SPE) represents a major concern, especially considering that in 2025 the Sun activity will be at its peak. Quantifying the amount and the effects of such exposure is therefore crucial, to identify shielding conditions that allow respecting the dose limits established by the various space agencies. By exploiting an interface between the BIANCA biophysical model and the FLUKA Monte Carlo radiation transport code, in this work we implemented a male and a female voxel phantom and we calculated absorbed doses and Gy-Eq doses in the various tissues/organs, as well as effective doses, following exposure to the August 1972 SPE, the most intense event of the modern era. The calculations were performed respect the organ dose limits for 30 d missions. A detailed comparison between male and female doses was then carried out, also considering that the Artemis II crew will include a woman. The results showed that female doses tend to be higher than male doses, especially with light shielding. This should be taken into account in mission design, also considering that, in a typical lunar mission, up to 15% of time may be spent in extra-vehicular activities, and thus with light shielding. More generally, this work outlines the importance of performing separate calculations for male and female astronauts when dealing with radiation doses and effects.

Ionizing radiation is widely used in medicine, both as a diagnostic tool and as a therapeutic agent [...].

In addition to the continuous exposure to cosmic rays, astronauts in space are occasionally exposed to Solar Particle Events (SPE), which involve less energetic particles but can deliver much higher doses. The latter can exceed several Gy in a few hours for the most intense SPEs, for which non-stochastic effects are thus a major concern. To identify adequate shielding conditions that would allow respecting the dose limits established by the various space agencies, the absorbed dose in the considered organ/tissue must be multiplied by the corresponding Relative Biological Effectiveness (RBE), which is a complex quantity depending on several factors including particle type and energy, considered biological effect, level of effect (and thus absorbed dose), etc.While in several studies only the particle-type dependence of RBE is taken into account, in this work we developed and applied a new approach where, thanks to an interface between the FLUKA Monte Carlo transport code and the BIANCA biophysical model, the RBE dependence on particle energy and absorbed dose was also considered. Furthermore, we included in the considered SPE spectra primary particles heavier than protons, which in many studies are neglected. This approach was then applied to the October 2003 SPE (the most intense SPE of solar cycle 23, also known as “Halloween event”) and the January 2005 event, which was characterized by a lower fluence but a harder spectrum, i.e., with higher-energy particles. The calculation outcomes were then discussed and compared with the current dose limits established for skin and blood forming organs in case of 30-days missions.This work showed that the BIANCA model, if interfaced to a radiation transport code, can be used to calculate the RBE values associated to Solar Particle Events. More generally, this work emphasizes the importance of taking into account the RBE dependence on particle energy and dose when calculating equivalent doses.

The FLUKA Monte Carlo Radiation Transport and Interaction code package is widely used to simulate the interaction of particles with matter in a variety of fields, including high energy physics, space radiation, medical applications, radiation protection and shielding assessments, accelerator studies, astrophysical studies and well logging. This paper gives a brief overview of the FLUKA program and describes recent developments, in particular, improvements in the modelling of particle interactions and transport are described in detail. In addition, an overview of selected applications is given.

The next years will see the completion of the radioactive ion beam facility SPES (Selective Production of Exotic Species) and the upgrade of the accelerators complex at Istituto Nazionale di Fisica Nucleare – Legnaro National Laboratories (LNL) opening up new possibilities in the fields of nuclear structure, nuclear dynamics, nuclear astrophysics, and applications. The nuclear physics community has organised a workshop to discuss the new physics opportunities that will be possible in the near future by employing state-of-the-art detection systems. A detailed discussion of the outcome from the workshop is presented in this report.

Long-term human space missions such as a future journey to Mars could be characterized by several hazards, among which radiation is one the highest-priority problems for astronaut health. In this work, exploiting a pre-existing interface between the BIANCA biophysical model and the FLUKA Monte Carlo transport code, a study was performed to calculate astronaut absorbed doses and equivalent doses following GCR exposure under different shielding conditions. More specifically, the interface with BIANCA allowed us to calculate both the RBE for cell survival, which is related to non-cancer effects, and that for chromosome aberrations, related to the induction of stochastic effects, including cancer. The results were then compared with cancer and non-cancer astronaut dose limits. Concerning the stochastic effects, the equivalent doses calculated by multiplying the absorbed dose by the RBE for chromosome aberrations (“high-dose method”) were similar to those calculated using the Q-values recommended by ICRP. For a 650-day mission at solar minimum (representative of a possible Mars mission scenario), the obtained values are always lower than the career limit recommended by ICRP (1 Sv), but higher than the limit of 600 mSv recently adopted by NASA. The comparison with the JAXA limits is more complex, since they are age and sex dependent. Concerning the deterministic limits, even for a 650-day mission at solar minimum, the values obtained by multiplying the absorbed dose by the RBE for cell survival are largely below the limits established by the various space agencies. Following this work, BIANCA, interfaced with an MC transport code such as FLUKA, can now predict RBE values for cell death and chromosome aberrations following GCR exposure. More generally, both at solar minimum and at solar maximum, shielding of 10 g/cm2 Al seems to be a better choice than 20 g/cm2 for astronaut protection against GCR.

The REMIX project is focused on the cyclotron-based production of 47 Sc, 149 Tb, 152 Tb, 155 Tb and 161 Tb radionuclides, whose decay characteristics make them suitable for medical applications. This work will outline the main results achieved withing the REMIX collaboration, that is organized in the following Work Packages (WP): WP1. Target manufacturing ( 49 Ti, 50 Ti and 155 Gd 2 O 3 ) and characterization; WP2. Nuclear cross section (XS) measurements with 49 Ti and 50 Ti targets for 47 Sc production; WP3. Nuclear XS measurements with nat Dy, 159 Tb and nat Eu targets for xx Tb production; WP4. Nuclear XS modeling for 47 Sc and 155 Tb production; WP5. Dosimetric calculations for 47 Sc- and xx Tb-labelled radiopharmaceuticals; WP6. 155 Tb Thick Target Yield (TTY) measurements; WP7. Apparatus design and realization for irradiation tests with the LARAMED beamline. Since the LARAMED bunkers and ancillary laboratories are currently under completion at the INFN-LNL, the nuclear XS experiments are carried out in collaboration with the GIP ARRONAX facility (Saint-Herblain, France) and the Thick Target Yield (TTY) measurements are performed at the Sacro Cuore Don Calabria hospital (SCDCh, Negrar, Verona, Italy).

BIANCA (BIophysical ANalysis of Cell death and chromosome Aberrations) is a biophysical model, implemented as a Monte Carlo code, which simulates the induction of chromosome aberrations and cell death by different monochromatic ion beams (i.e., different ion types and energy values), as well as photons. In previous works, the model predictions for cell survival and lymphocyte dicentrics along therapeutic-like ion beams have been successfully benchmarked against experimental data. With the aim of evaluating the biological damage induced by Galactic Cosmic Rays (GCR), in this study BIANCA was extended up to Fe-ions. A radiobiological database describing human skin fibroblast cell survival and lymphocyte dicentrics as a function of ion type (1≤Z≤26) and energy, as well as dose, was constructed. Afterwards, interfacing BIANCA with the FLUKA Monte Carlo transport code, a feasibility study was performed to calculate the Relative Biological Effectiveness (RBE) of Galactic Cosmic Rays, both for dicentrics and for cell survival; the results were discussed with respect to available space radiation protection limits. Following this work, BIANCA can now provide RBE predictions of cell killing, which can be related to deterministic effects, and lymphocyte dicentrics, more related to stochastic effects, for space radiation exposure.

Objective. The main objective of this work consists of applying, for the first time, the BIANCA (BIophysical ANalysis of Cell death and chromosome Aberrations) biophysical model to the RBE calculation for C-ion cancer patients, and comparing the outcomes with those obtained by the LEM I model, which is applied in clinics. Indeed, the continuous development of heavy-ion cancer therapy requires modelling of biological effects of ion beams on tumours and normal tissues. The relative biological effectiveness (RBE) of heavy ions is higher than that of protons, with a significant variation along the beam path. Therefore, it requires a precise modelling, especially for the pencil-beam scanning technique. Currently, two radiobiological models, LEM I and MKM, are in use for heavy ions in scanned pencil-beam facilities. Approach. Utilizing an interface with the FLUKA Particle Therapy Tool, BIANCA was applied to re-calculate the RBE-weighted dose distribution for carbon-ion treatment of three patients (chordoma, head-and-neck and prostate) previously irradiated at CNAO, where radiobiological optimization was based on LEM I. The predictions obtained by BIANCA were based either on chordoma cell survival (RBE surv ), or on dicentric aberrations in peripheral blood lymphocytes (RBE ab ), which are indicators of late normal tissue damage, including secondary tumours. The simulation outcomes were then compared with those provided by LEM I. Main results. While in the target and in the entrance channel BIANCA predictions were lower than those obtained by LEM I, the two models provided very similar results in the considered OAR. The observed differences between RBE surv and RBE ab (which were also dependent on fractional dose and LET) suggest that in normal tissues the information on cell survival should be integrated by information more closely related to the induction of late damage, such as chromosome aberrations. Significance. This work showed that BIANCA is suitable for treatment plan optimization in ion-beam therapy, especially considering that it can predict both cell survival and chromosome aberrations and has previously shown good agreement with carbon-ion experimental data.

Space research seems to be object of a renewed interest, also considering that human missions to the Moon, and possibly Mars, are being planned. Among the risks affecting such missions, astronauts' exposure to space radiation is a major concern. In this work, the question of the evaluation of biological damage by Galactic Cosmic Rays (GCR) was addressed by a biophysical model called BIophysical ANalysis of Cell death and chromosome Aberrations (BIANCA), which simulates the induction of cell death and chromosome aberrations by different ions. While previously BIANCA has been validated for calculating cell death along hadrontherapy beams up to oxygen, herein the approach was extended up to Fe ions. Specifically, experimental survival curves available in literature for V79 cells irradiated by Si-, Ne-, Ar- and Fe-ions were reproduced, and a reference radiobiological database describing V79 cell survival as a function of ion type (1 ⩽Z⩽ 26), energy and dose was constructed. Analogous databases were generated for Chinese hamster ovary hamster cells and human skin fibroblasts, finding good agreement between simulations and data. Concerning chromosome aberrations, which are regarded as radiation risk biomarkers, dicentric data in human lymphocytes irradiated by heavy ions up to iron were reproduced, and a radiobiological database allowing calculation of lymphocyte dicentric yields as a function of dose, ion type (1 ⩽Z⩽ 26) and energy was constructed. Following interface between BIANCA and the FLUKA Monte Carlo transport code, a feasibility study was performed to calculate the relative biological effectiveness (RBE) of different GCR spectrum components, for both dicentrics and cell death. Fe-ions, although representing only 10% of the total absorbed dose, were found to be responsible for about 35%-40% of the RBE-weighted dose. Interestingly, the RBE for dicentrics was higher than that for cell survival. More generally, this work shows that BIANCA can calculate RBE values for cell death and lymphocyte dicentrics not only for ion therapy, but also for space radiation.

Radioisotope $^{52g}$Mn is of special interest for multimodal imaging. Using state-of-art nuclear reaction codes, we study the alternative nuclear reaction route $^{nat}$V($\alpha$,x)$^{52g}$Mn in comparison with the standard production routes based upon the use of chromium targets. The integral yields of $^{52g}$Mn and contaminants have been evaluated. The main outcome of this investigation is that the production of the main contaminant isotope $^{54}$Mn is expected to be lower than with $^{nat}$Cr. The study also reveals a large spread in the cross-section data set and points out the need of more precise measurements of the reaction $^{nat}$V($\alpha$,x)$^{52g}$Mn as well as the need of a more accurate theoretical description.

The conversion electrons and gamma-rays emitter Sn-117m is a promising theranostic radionuclide produced mainly at nuclear reactors with low specific activity. The variety of possible applications suggests the necessity of a larger production, more likely reachable at cyclotrons. The irradiation of Cd-nat and In-nat targets with the 30 MeV alpha-beam, available at the Heavy Ion Laboratory (HIL) of Warsaw, aims to measure the production cross-sections of Sn-117m and its contaminants. Theoretical calculations are also performed to support the experimental results.

New data for the $^\mbox{nat}$V(p,x) reactions have been measured in the range 26-70 MeV, with production of the nuclides $^{47}$Sc, $^{43}$Sc, $^{44m}$Sc, $^{44g}$Sc, $^{46}$Sc, $^{48}$Sc, $^{42}$K, $^{43}$K, $^{48}$V, $^{48}$Cr, $^{49}$Cr, and $^{51}$Cr. The focus is on the production of $^{47}$Sc, a $\beta^-$-emitter suitable for innovative radiotheranostic applications in nuclear medicine. The measured cross sections for this radionuclide and its contaminants are compared with the theoretical excitation functions calculated with the TALYS code. In view of novel radiopharmaceutical applications, it is essential to accurately describe these cross-sections for the evaluation of yields, purities, and dose releases. Hence, we optimize the level-density parameters of the microscopic models in the TALYS code to obtain the best possible descriptions of the new data. We consider different irradiation conditions to estimate the production yields from the cross sections determined in this work.

Chromosome aberrations are widely considered among the best biomarkers of radiation health risk due to their relationship with late cancer incidence. In particular, aberrations in peripheral blood lymphocytes (PBL) can be regarded as indicators of hematologic toxicity, which is a major limiting factor of radiotherapy total dose. In this framework, a radiobiological database describing the induction of PBL dicentrics as a function of ion type and energy was developed by means of the BIANCA (BIophysical ANalysis of Cell death and chromosome Aberrations) biophysical model, which has been previously applied to predict the effectiveness of therapeutic-like ion beams at killing tumour cells. This database was then read by the FLUKA Monte Carlo transport code, thus allowing us to calculate the Relative Biological Effectiveness (RBE) for dicentric induction along therapeutic C-ion beams. A comparison with previous results showed that, while in the higher-dose regions (e.g., the Spread-Out Bragg Peak, SOBP), the RBE for dicentrics was lower than that for cell survival. In the lower-dose regions (e.g., the fragmentation tail), the opposite trend was observed. This work suggests that, at least for some irradiation scenarios, calculating the biological effectiveness of a hadrontherapy beam solely based on the RBE for cell survival may lead to an underestimation of the risk of (late) damage to healthy tissues. More generally, following this work, BIANCA has gained the capability of providing RBE predictions not only for cell killing, but also for healthy tissue damage.

While cancer therapy with protons and C-ions is continuously spreading, in the near future patients will be also treated with He-ions which, in comparison to photons, combine the higher precision of protons with the higher relative biological effectiveness (RBE) of C-ions. Similarly to C-ions, also for He-ions the RBE variation along the beam must be known as precisely as possible, especially for active beam delivery systems. In this framework the BIANCA biophysical model, which has already been applied to calculate the RBE along proton and C-ion beams, was extended to4He-ions and, following interface with the FLUKA code, was benchmarked against cell survival data on CHO normal cells and Renca tumour cells irradiated at different positions along therapeutic-like4He-ion beams at the Heidelberg Ion-beam Therapy centre, where the first He-ion patient will be treated soon. Very good agreement between simulations and data was obtained, showing that BIANCA can now be used to predict RBE following irradiation with all ion types that are currently used, or will be used soon, for hadrontherapy. Thanks to the development of a reference simulation database describing V79 cell survival for ion and photon irradiation, these predictions can be cell-type specific because analogous databases can be produced, in principle, for any cell line. Furthermore, survival data on CHO cells irradiated by a He-3 beam were reproduced to compare the biophysical properties of He-4 and He-3 beams, which is currently an open question. This comparison showed that, at the same depth, He-4 beams tend to have a higher RBE with respect to He-3 beams, and that this difference is also modulated by the considered physical dose, as well as the cell radiosensitivity. However, at least for the considered cases, no significant difference was found for the ratio between the RBE-weighted dose in the SOBP and that in the entrance plateau.

In cancer hadrontherapy, the Relative Biological Effectiveness (RBE) is calculated by considering cell survival as the endpoint of interest. Although this is a good estimator of the beam effectiveness in eliminating the tumour cells, late damage in healthy tissues, including secondary tumours, is better correlated with chromosomal aberrations. In particular, dicentrics in blood lymphocytes are widely considered as a good biomarker of normal tissue damage, as the blood circulates in all tissues and is inevitably exposed to radiation during the treatment. In this study, lymphocyte dicentrics were used as an ad hoc endpoint to evaluate the RBE for (late) normal tissue damage by means of BIANCA (BIophysical ANalysis of Cell death and chromosome Aberrations), a biophysical model that simulates radiation-induced chromosome aberrations and cell death. More specifically, BIANCA was applied to produce a radiobiological database that predicts lymphocyte dicentric induction as a function of dose, particle type and LET. Afterwards, an interface with the FLUKA code allowed predicting dicentric RBE along a C-ion SOBP, and comparing it with cell survival RBE. This pilot study suggested that using the RBE for tumour cell survival along the entire beam might lead to an underestimation of the risk of normal tissue damage.

Metastable Sn-117m is a promising theranostic radionuclide, suitable for SPECT diagnostic imaging and conversion electron therapy. Its production is based mainly on nuclear reactors, but there is increasing interest in alternative routes with cyclotrons. Theoretical studies are essential to identify the irradiation parameters and conditions to maximize its production, while minimizing the impact of the contaminants. The goal of this study is to investigate the production of Sn-117m with a 30MeV a beam on Cd-nat and In-nat targets, as provided by the HIL-UW (Heavy Ion Laboratory - University of Warsaw) U-200P cyclotron. We performed a theoretical analysis of cross section, yield and purity by means of two nuclear reaction codes: Talys (v.1.9), based on a combination of models, and Fluka (v.2018.2.dev), based on Monte Carlo simulations. We compared the theoretical calculations with both experimental data already known in the literature and preliminary results obtained at HIL. A statistical treatment of the models suggests a comparable production of Sn-117m for both targets, but a higher radionuclidic purity was found in the case of the In-nat target.

We have introduced a tool to describe in a simple and efficient way the outcomes of known nuclear reaction codes. It differs from the customary use where typically a specific single model is selected and the remaining disregarded. The use of simple statistical procedures allows to introduce a more general theoretical evaluation with quantitative uncertainty, constructed on the variability of the built-in theoretical models. We apply the technique to study the production of $^{47}$Sc (a radio-nuclide with potential theranostic applications in nuclear medicine) with a proton beam impinging on a thick natural Vanadium target. We find an energy range with significant production of $^{47}$Sc, and a minimum co-production of $^{46}$Sc, the radioactive contaminant that has to be avoided as much as possible because of its much longer half life than $^{47}$Sc (83.79 d vs 3.3492 d).