RESUMO
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.
Assuntos
Radiação Cósmica , Eficiência Biológica Relativa , Atividade Solar , Radiação Cósmica/efeitos adversos , Humanos , Voo Espacial , Método de Monte Carlo , Astronautas , Doses de RadiaçãoRESUMO
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.
Assuntos
Neoplasias , Terapia com Prótons , Animais , Cricetinae , Cricetulus , Humanos , Neoplasias/radioterapia , Prótons , Eficiência Biológica RelativaRESUMO
In the framework of RBE modelling for hadron therapy, the BIANCA biophysical model was extended to O-ions and was used to construct a radiobiological database describing the survival of V79 cells as a function of ion type (1 ⩽ Z ⩽ 8) and energy. This database allowed performing RBE predictions in very good agreement with experimental data. A method was then developed to construct analogous databases for different cell lines, starting from the V79 database as a reference. Following interface to the FLUKA Monte Carlo radiation transport code, BIANCA was then applied for the first time to predict cell survival in a typical patient treatment scenario, consisting of two opposing fields of range-equivalent protons or C-ions. The model predictions were found to be in good agreement with CHO cell survival data obtained at the Heidelberg ion-beam therapy (HIT) centre, as well as predictions performed by the local effect model (version LEM IV). This work shows that BIANCA can be used to predict cell survival and RBE not only for V79 and AG01522 cells, as shown previously, but also, in principle, for any cell line of interest. Furthermore, following interface to a transport code like FLUKA, BIANCA can provide predictions of 3D biological dose distributions for hadron therapy treatments, thus laying the foundations for future applications in clinics.
Assuntos
Benchmarking , Partículas Elementares/uso terapêutico , Radioterapia com Íons Pesados/métodos , Método de Monte Carlo , Planejamento da Radioterapia Assistida por Computador/métodos , Animais , Células CHO , Sobrevivência Celular , Cricetinae , Cricetulus , Humanos , Eficiência Biológica RelativaRESUMO
The present work is part of a preclinical in vitro study to assess the efficacy of BNCT applied to liver or lung coloncarcinoma metastases and to limb osteosarcoma. Adherent growing cell lines can be irradiated as adherent to the culture flasks or as cell suspensions, differences in radio-sensitivity of the two modalities of radiation exposure have been investigated. Dose related cell survival and cell cycle perturbation results evidenced that the radiosensitivity of adherent cells is higher than that of the suspended ones.
Assuntos
Terapia por Captura de Nêutron de Boro , Adesão Celular/efeitos da radiação , Raios gama , Neoplasias/radioterapia , Nêutrons , Animais , Ciclo Celular/efeitos da radiação , Linhagem Celular Tumoral , Neoplasias/patologia , RatosRESUMO
Some open questions on the mechanisms underlying radiation-induced cell death were addressed by a biophysical model, focusing on DNA damage clustering and its consequences. DNA "cluster lesions" (CLs) were assumed to produce independent chromosome fragments that, if created within a micrometer-scale threshold distance (d), can lead to chromosome aberrations following mis-rejoining; in turn, certain aberrations (dicentrics, rings and large deletions) were assumed to lead to clonogenic cell death. The CL yield and d were the only adjustable parameters. The model, implemented as a Monte Carlo code called BIophysical ANalysis of Cell death and chromosome Aberrations (BIANCA), provided simulated survival curves that were directly compared with experimental data on human and hamster cells exposed to photons, protons, α-particles and heavier ions including carbon and iron. d = 5 µm, independent of radiation quality, and CL yields in the range ~2-20 CLs Gy(-1) cell(-1), depending on particle type and energy, led to good agreement between simulations and data. This supports the hypothesis of a pivotal role of DNA cluster damage at sub-micrometric scale, modulated by chromosome fragment mis-rejoining at micrometric scale. To investigate the features of such critical damage, the CL yields were compared with experimental or theoretical yields of DNA fragments of different sizes, focusing on the base-pair scale (related to the so-called local clustering), the kbp scale ("regional clustering") and the Mbp scale, corresponding to chromatin loops. Interestingly, the CL yields showed better agreement with kbp fragments rather than bp fragments or Mbp fragments; this suggests that also regional clustering, in addition to other clustering levels, may play an important role, possibly due to its relationship with nucleosome organization in the chromatin fiber.