Antonio Italiano

Monte Carlo study of the dose enhancement effect of gold nanoparticles during X-ray therapies and evaluation of the anti-angiogenic effect on tumour capillary vessels

Gold nanoparticles (GNPs) are a promising radiosensitizer agent in radiotherapy. Through a simulation performed with the Geant4 Monte Carlo code, we evaluated the dose enhancement effect of GNPs during therapies with an x-ray tube operating at 150 kV (E = 55 keV and E(max) = 150 keV) and we studied the impact of GNP diffusion out of the tumour vessels, in terms of antiangiogenic and cytotoxic effects. Firstly, a single x-ray beam was assumed to irradiate a parallelepiped volume of soft tissue, in which a GNP-doped target volume was placed at different depths. Average dose enhancement factors (DEF) in presence of GNPs were obtained as a function of the target depth and GNP concentration, uniformly distributed; values ranging between 1.6 for 10 mg Au/g at 0 cm and 7.2 for 200 mg Au/g at 5 cm were determined. Furtherly, a second geometry was adopted, in which a blood capillary vessel (10 μm thick and 10 μm of inner radius) was placed at the centre of a cubic volume of soft tissue; doses and DEFs to the capillary endothelium as well as to the surrounding viable tumour were evaluated, for different models of GNP diffusion. Our results indicate that the radial DEF profiles around the vessel are in close relationship with the radial profiles of GNP concentration assumed, except for at sharp gradients of concentration. DEFs at the endothelium ranged from 1.6 to 6.5, for GNP concentrations in the blood of 10 and 200 mg/ml, respectively. These data can be helpful for the development of new and more specific GNP-based radiosensitizers of potential interest in radiotherapy, exploiting the combined benefit of anti-angiogenic and cytotoxic dose enhancement effects.

A Monte Carlo approach to small-scale dosimetry of solid tumour microvasculature for nuclear medicine therapies with 223Ra-, 131I-, 177Lu- and 111In-labelled radiopharmaceuticals

The small-scale dosimetry of radionuclides in solid-tumours is directly related to the intra-tumoral distribution of the administered radiopharmaceutical, which is affected by its egress from the vasculature and dispersion within the tumour. The aim of the present study was to evaluate the combined dosimetric effects of radiopharmaceutical distribution and range of the emitted radiation in a model of tumour microvasculature. We developed a computational model of solid-tumour microenvironment around a blood capillary vessel, and we simulated the transport of radiation emitted by (223)Ra, (111)In, (131)I and (177)Lu using the GEANT4 Monte Carlo. For each nuclide, several models of radiopharmaceutical dispersion throughout the capillary vessel were considered. Radial dose profiles around the capillary vessel, the Initial Radioactivity (IR) necessary to deposit 100 Gy of dose at the edge of the viable tumour-cell region, the Endothelial Cell Mean Dose (ECMD) and the Tumour Edge Mean Dose (TEMD), i.e. the mean dose imparted at the 250-μm layer of tissue, were computed. The results for beta and Auger emitters demonstrate that the photon dose is about three to four orders of magnitude lower than that deposited by electrons. For (223)Ra, the beta emissions of its progeny deliver a dose about three orders of magnitude lower than that delivered by the alpha emissions. Such results may help to characterize the dose inhomogeneities in solid tumour therapies with radiopharmaceuticals, taking into account the interplay between drug distribution from vasculature and range of ionizing radiations.

Absorbed fractions for alpha particles in ellipsoidal volumes

Internal dosimetry of alpha particles is gaining attention due to the increasing applications in cancer treatment and also for the assessment of environmental contamination from radionuclides. We developed a Monte Carlo simulation in GEANT4 in order to calculate the absorbed fractions for monoenergetic alpha particles in the energy interval between 0.1 and 10 MeV, uniformly distributed in ellipsoids made of soft tissue. For each volume, we simulated a spherical shape, three oblate and three prolate ellipsoids, and one scalene shape. For each energy and for every geometrical configuration, an analytical relationship between the absorbed fraction and a generalized radius was found; and the dependence of the fit parameters on the alpha energy is discussed and fitted by parametric functions. With the proposed formulation, the absorbed fraction for alpha particles in the energy range explored can be calculated for volumes and for ellipsoidal shapes of practical interest. This method can be applied to the evaluation of absorbed fraction from alpha-emitting radionuclides. The contribution to the deposited energy coming from electron and photon emissions can be accounted for exploiting the specific formulations previously introduced. As an example of application, the dosimetry of (213)Bi and its decay chain in ellipsoids is reported.

Evaluation of skin absorbed doses during manipulation of radioactive sources: a comparison between VARSKIN code and Monte Carlo simulations

The evaluation of skin doses during manipulation of radioactive sources can be a critical issue for which the most accurate calculation strategies available should be used. The aim of this work was to compare the results of the analytical approach used in VARSKIN with the simulation of radiation transport and interaction by Monte Carlo calculations in GAMOS (GEANT4-based Architecture for Medicine-Oriented Simulations), and to provide an accurate and versatile tool for the evaluation of skin doses from radionuclide sources of any realistic shape (e.g. cylindrical, parallelepiped), even in the presence of multiple interposed absorber layers. A set of 20 radionuclides (pure β, β-γ, Auger and γ emitters) from among the most frequently employed in nuclear medicine and laboratory practices were selected for comparison. We studied a point-like and a cylindrical source, in the presence of varying thicknesses of absorbing layers. We found a general agreement for most nuclides when the source was directly in contact with skin or in the presence of a thin layer of absorbing material. However, when the thickness of the absorber increased, significant differences were found for several nuclides. In these cases, the proposed method based on a dedicated Monte Carlo simulation could give more accurate results in a reasonable time, which could optimise accuracy when assessing skin doses in routine as well as incidental exposure scenarios.

Future laser-accelerated proton beams at ELI-Beamlines as potential source of positron emitters for PET

The development of novel compact PET radionuclide production systems is of great interest to promote the diffusion of PET diagnostics, especially in view of the continuous development of novel, fast and efficient, radiopharmaceutical methods of labeling. We studied the feasibility to produce clinically-relevant amounts of PET isotopes by means of laser-accelerated proton sources expected at the ELI-Beamlines facility where a PW, 30 fs, 10 Hz laser system will be available. The production yields of several positron emitters were calculated through the TALYS software, by taking into account three possible scenarios of broad proton spectra expected, with maximum energies ranging from about 8 MeV to 100 MeV. With the hypothesized proton fluencies, clinically-relevant amounts of radionuclides can be obtained, suitable to prepare single doses of radiopharmaceuticals exploiting modern fast and efficient labeling systems.

An analytical model for calculating internal dose conversion coefficients for non-human biota

To assess the radiation burden of non-human living organisms, dose coefficients are available in the literature, precalculated by assuming an ellipsoidal shape of each organism. A previously developed analytical method was applied for the determination of absorbed fractions inside ellipsoidal volumes from alpha, beta, and gamma radiations to the calculation of dose conversion coefficients (DCCs) for 15 reference organisms, animals and plants, either terrestrial, amphibian, or aquatic, and six radionuclides (14C, 90Sr, 60Co, 137Cs, 238U, and 241Am). The results were compared with the reference values reported in Publication 108 of the International Commission on Radiological Protection, in which a different calculation approach for DCCs was employed. The results demonstrate that the present analytical method, originally intended for applications in internal dosimetry of nuclear medicine therapy, gives consistent results for all the beta-, beta–gamma-, and alpha-emitting radionuclides tested in a wide range of organism masses, between 8xa0mg and 1.3xa0kg. The applicability of the method proposed can take advantage from its ease of implementation in an ordinary electronic spreadsheet, allowing to calculate, for virtually all possible radionuclide emission spectra, the DCCs for ellipsoidal models of non-human living organisms in the environment.

Patient dose in image guided radiotherapy: Monte Carlo study of the CBCT dose contribution

Image Guided RadioTherapy (IGRT) is a technique whose diffusion is growing thanks to the well-recognized gain in accuracy of dose delivery. However, multiple Cone Beam Computed Tomography (CBCT) scans add dose to patients, and its contribution has to be assessed and minimized. Aim of our work was to evaluate, through Monte Carlo simulations, organ doses in IGRT due to CBCT and therapeutic MV irradiation in head-neck, thorax and pelvis districts. We developed a Monte Carlo simulation in GAMOS (Geant4-based Architecture for Medicine-Oriented Simulations), reproducing an Elekta Synergy medical linac operating at 6 and 10 MV photon energy, and we set up a scalable anthropomorphic model. After a validation by comparison with the experimental quality indexes, we evaluated the average doses to all organs and tissues belonging to the model for the three cases of irradiated district. Scattered radiation in therapy is larger than that diffused by CBCT by one to two orders of magnitude.

Evaluation of the production capabilities of 18 F, 11 C, 13 N and 15 O PET isotopes at the PET-cyclotron-radiochemistry site of Messina University

The production of 18 F, 11 C, 13 N, and 15 O positron emitting radionuclides for PET imaging is usually accomplished in Nuclear Medicine Departments through direct nuclear reactions induced by protons accelerated by compact medical cyclotrons on liquid or gaseous targets. Messina University has funded the construction of a PET-cyclotron-radio-chemistry plant at the Messina University Hospital, equipped with a 11 MeV self-shielded cyclotron. We estimated the expected production yields of these nuclides, accounting for target thickness, production of other radioactive nuclides, and time effects on the irradiated target purity. To this aim, both TALYS code (v. 1.8) and an analytical approach based on EXFOR experimental data were used. The general agreement between the two approaches, and with the available literature data, allows to assess the expected yields at the End of Bombardment, and relative target purities, to be used for further radiopharmaceutical preparation steps.

Production of 68 Ge , 64 Cu , 86 Y , 89 Zr , 73 Se , 77 Br and 124 I positron emitting radionuclides through future laser-accelerated proton beams at ELI-Beamlines for innovative PET diagnostics

The development of innovative production pathways for high-Z positron emitters is of great interest to enlarge the applicability of PET diagnostics, especially in view of the continuous development of new radiopharmaceuticals. We evaluated the theoretical yields of 64 Cu , 86 Y , 89 Zr , 73 Se , 77 Br and 124 I PET isotopes, plus the 68 Ge isotope, parent of the 68 Ga positron emitter, in the hypothesis of production through laser-accelerated proton sources expected at the ELI-Beamlines facility. By means of the TALYS software we simulated the nuclear reactions leading to the above radionuclides, hypothesizing three possible scenarios of broad proton spectra, with maximum energies of about 9, 40 and 100 MeV. The production yields of the studied radionuclides, within the expected fluences, appear to be suitable for pre-clinical applications.