An interface between the FLUKA transport code and the BIANCA biophysical model to predict the biological effectiveness of hadrontherapy beams

In the context of cell death induced by ionizing radiation, the BIANCA biophysical model was used to produce tables of biological effectiveness, in terms of α and β parameters typical of the linear quadratic model for cell survival curves; the tables were produced for irradiation by protons, helium ions and carbon ions over a wide energy range and for two cell lines of different radiosensitivity. By using these values, the predictions of BIANCA were compared with experimental data of RBE, and good agreement was found. After this validation step, the FLUKA radiation transport code, which can produce physical dose profiles for typical hadrontherapy beams, could read the α and β tables; thanks to such an interface between FLUKA and BIANCA, probabilities of cell death were predicted along depth-dose profiles. An example of a carbon spread out Bragg peak is shown, highlighting the differences in the biological response of different cell lines and the possible importance of using more than one cell line in the context of treatment plan optimization

Production of high purity 52g^{52g}Mn from nat^{nat}V targets with α\alpha-beams at cyclotrons

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.Comment: Keywords: Cyclotron radionuclide production, $^{52g}$Mn, $^{53}$Mn, $^{54}$Mn, multi-modal imaging,{\alpha}-induced reactions, nuclear reactions modelin

Biophysical modelling of proximity effects in chromosome aberration production

Although two chromosome breaks induced in proximity are known to have a higher probability of being (mis-)rejoined, several aspects of these “proximity effects” are still unclear. Herein, proximity effects in human lymphocytes and fibroblasts were investigated by the BIANCA biophysical model, describing the dependence of the rejoining probability on the break initial distance, r, either by an exponential function of the form exp(−r/r0), or by a Gaussian function of the form exp(−r2/2σ2). The characteristic distance (r0 or σ) was an adjustable parameter; the only other parameter was the yield of DNA “Cluster Lesions” (CLs), where a CL is defined as a critical damage producing two independent chromosome fragments. The comparison of the simulation outcomes with published experimental and theoretical works showed that an exponential function may describe proximity effects in both the considered cell types, and possibly other cells. Since this exponential behavior has been found to be consistent with confined diffusion of break ends, this also suggests that, at the relatively short times required for chromosome aberration production, (confined) diffusion is preferable to other mechanisms. Furthermore, the results suggested that the ratio of dicentrics to centric rings (“F-ratio”) may be a better high-LET fingerprint in lymphocytes, whereas the ratio of acentric to centric rings (“G-ratio”) may be a better one in fibroblasts

Radiation damage in biomolecules and cells

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

Modelling the induction of cell death and chromosome damage by therapeutic protons

A two-parameter biophysical model cal led BIANCA (BIophysical ANalysis of Cell death and chromosome Aberrations), which assumes a pivotal role for DNA cluster damage and for “lethal” chromosome aberrations, was applied to calculate cell death and chromosome aberrations for normal and radio-resistant cells along a 62-MeV eye melanoma proton beam. The yield of DNA “Cluster Lesions” and the probability for a chromosome fragment of not being rejoined with any partne r were adjustable parameters. In line with other works, the beam effectiveness at inducing both biological endpoints was found to increase with increasing depth, and high levels of damage were found also beyond the dose fall-off, due to the higher biological effectiveness of low-energy protons. This implies that assuming a constant RBE along the whole SOBP, as is currently done in clinical practice, may be sub-optimal, also implying a possible underestimation of normal tissue damage. Furthermore, the calculations suggested that for higher fractional doses, like those delivered in hypo-fractionation regimes, the relative increase in effectiven ess along the SOBP may be less pronounced than for lower fractional doses