G. Cuttone

Geant4 developments and applications

Geant4 is a software toolkit for the simulation of the passage of particles through matter. It is used by a large number of experiments and projects in a variety of application domains, including high energy physics, astrophysics and space science, medical physics and radiation protection. Its functionality and modeling capabilities continue to be extended, while its performance is enhanced. An overview of recent developments in diverse areas of the toolkit is presented. These include performance optimization for complex setups; improvements for the propagation in fields; new options for event biasing; and additions and improvements in geometry, physics processes and interactive capabilities

A 62 MeV proton beam for the treatment of ocular melanoma at Laboratori Nazionali del Sud-INFN (CATANIA)

At the INFN Laboratori Nazionali del Sud in Catania (Italy) the first Italian protontherapy facility, named CATANA (Centre di AdroTerapia e Applicazioni Nucleari Avanzate) has been realized in collaboration with the University of Catania. It is based on the use of the 62 MeV proton beam delivered by the K = 800 superconducting cyclotron installed and working at LNS since 1995. The facility is mainly devoted to the treatment of ocular diseases like uveal melanoma. A beam treatment line in air has been realized together with a dedicated positioning patient system. The facility is in operation since the beginning of 2002 and 52 patients have been successfully treated up to now. The main features of CATANA together with the clinical and dosimetric features will be extensively reported; particularly, will be described the proton beam line, that has been entirely realized at LNS, with all its elements, the experimental transversal and depth dose distributions of the 62 MeV proton beam obtained for a final collimator of 25 mm diameter and the experimental depth dose distributions of a modulated proton beam obtained for the same final collimator. Finally, the clinical results over one year of treatments, describing the features of the treated diseases will be reported.

An investigation of the operating characteristics of two PTW diamond detectors in photon and electron beams

The dosimetric properties of two PTW Riga diamond detectors type 60003 were studied in high-energy photon and electron therapy beam. Properties under study were current-voltage characteristic, polarization effect, time stability of response, dose response, dose-rate dependence, temperature stability, and beam quality dependence of the sensitivity factor. Differences were shown between the two detectors for most of the previous properties. Also, the observed behavior was, to some extent, different from what was reported in the PTW technical specifications. The necessity to characterize each diamond detector individually was addressed.

Cellular and molecular effects of protons: Apoptosis induction and potential implications for cancer therapy

Due to their ballistic precision, apoptosis induction by protons could be a strategy to specifically eliminate neoplastic cells. To characterize the cellular and molecular effects of these hadrons, we performed dose-response and time-course experiments by exposing different cell lines (PC3, Ca301D, MCF7) to increasing doses of protons and examining them with FACS, RT-PCR, and electron spin resonance (ESR). Irradiation with a dose of 10 Gy of a 26,7 Mev proton beam altered cell structures such as membranes, caused DNA double strand breaks, and significantly increased intracellular levels of hydroxyl ions, are active oxygen species (ROS). This modified the transcriptome of irradiated cells, activated the mitochondrial (intrinsic) pathway of apoptosis, and resulted in cycle arrest at the G2/M boundary. The number of necrotic cells within the irradiated cell population did not significantly increase with respect to the controls. The effects of irradiation with 20 Gy were qualitatively as well as quantitatively similar, but exposure to 40 Gy caused massive necrosis. Similar experiments with photons demonstrated that they induce apoptosis in a significantly lower number of cells and in a temporally delayed manner. These data advance our knowledge on the cellular and molecular effects of proton irradiation and could be useful for improving current hadrontherapy protocols.

Induction and Repair of DNA Double-Strand Breaks in Human Cells: Dephosphorylation of Histone H2AX and its Inhibition by Calyculin A

Abstract Antonelli, F., Belli, M., Cuttone, G., Dini, V., Esposito, G., Simone, G., Sorrentino, E. and Tabocchini, M. A. Induction and Repair of DNA Double-Strand Breaks in Human Cells: Dephosphorylation of Histone H2AX and its Inhibition by Calyculin A. Radiat. Res. 164, 514–517 (2005). Phosphorylation of histone H2AX at serine 139 (γ-H2AX) represents one of the earliest steps in DNA DSB signaling and repair, but the mechanisms of coupling this histone modification to DSB processing remain to be established. In this work, H2AX phosphorylation-dephosphorylation kinetics induced by low doses of γ rays in MRC-5 human fibroblasts was studied. The number of γ-H2AX foci increased rapidly, with the maximum reached 20 min after irradiation. Using calyculin A, a protein phosphatase inhibitor, no significant dephosphorylation was found in this time. At longer times, no further induction of γ-H2AX foci occurred. This indicates that the number of γ-H2AX foci scored at 20 min can be used as representative of the initial number of DSBs. Pulsed-field gel electrophoresis (PFGE) was also used to determine whether calyculin A-mediated inhibition of γ-H2AX dephosphorylation and DSB rejoining are independent phenomena. We found that the maintenance of the phosphate group at Ser 139 in γ-H2AX does not represent an obstacle for DSB rejoining. Preliminary experiments performed with 62 MeV/nucleon carbon ions have shown a longer persistence of γ-H2AX foci with respect to γ rays, consistent with the induction of damage that is more severe and difficult to repair.

Characterisation of CVD diamond dosimeters in on-line configuration

Abstract The high sensitivity and the nearly tissue equivalence of diamond make it a material suitable as detector for on-line dosimetry. The tremendous development of the CVD diamond technology allows to employ polycrystalline diamond films with controlled dimensions and a potential low cost as on-line radiation dosimeters. In this paper a characterisation and a comparison of the response of two “detector-grade” CVD diamond films under photon and electron beams are presented. The results show that both samples can be used as on-line dosimeters for applications in radiotherapy.

Characterization of a Silicon Strip Detector and a YAG:Ce Calorimeter for a Proton Computed Radiography Apparatus

Today, there is a steadily growing interest in the use of proton beams for tumor therapy, as they permit to tightly shape the dose delivered to the target reducing the exposure of the surrounding healthy tissues. Nonetheless, accuracy in the determination of the dose distribution in proton-therapy is up to now limited by the uncertainty in stopping powers, which are presently calculated from the photon attenuation coefficients measured by X-ray tomography. Proton computed tomography apparatus (pCT) has been proposed to directly measure the stopping power and reduce this uncertainty. Main problem with proton imaging is the blurring effect introduced by multiple Coulomb scattering: single proton tracking is a promising technique to face this difficulty. As a first step towards a pCT system, we designed a proton radiography (pCR) prototype based on a silicon microstrip tracker (to characterize particle trajectories) and a segmented YAG:Ce calorimeter (to measure their residual energy). Aim of the system is to detect protons with a ~1 MHz particle rate of and with kinetic energy in the range 250-270 MeV, high enough to pass through human body. Design and development of the pCR prototype, as well as the characterization of its single components, are described in this paper.

Radiobiological analysis of human melanoma cells on the 62 MeV CATANA proton beam

Purpose: To measure the ability of protons and γ-rays to effect cell viability and cell survival of human HTB140 melanoma cells. Materials and methods: Exponentially growing HTB140 cells were irradiated close to the Bragg peak maximum of the 62 MeV protons or with 60Co γ-rays with single doses, ranging from 8 – 24 Gy. Cell viability using the 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT) assay was evaluated at 6 h, 24 h, 48 h or 7 days after irradiation and clonogenic survival was assessed at 7 days after irradiation. Cell cycle phase redistribution and the level of apoptosis were evaluated at 6 h and 48 h after irradiation. Results: The study of cell viability as a function of time (cell survival progression) and cell survival, using a clonal assay, demonstrated the considerably stronger inactivation effect of protons compared to γ-rays with a relative biological effectiveness (RBE) of ∼1.64. Cell cycle phase distribution and apoptosis levels with time enabled us to investigate the development and the character of the damage induced by irradiation. Due to the high radio-resistance of HTB140 cells, cell cycle phase redistribution exhibited only a modest cell accumulation in G2/M phase. Protons but not γ-rays induced apoptosis. Conclusions: It appears that protons reduce the number of HTB140 cells by apoptosis as well as by severe DNA damage, while γ-rays eliminate viable cells primarily by the production of irreparable DNA damage. Protons have an increased RBE relative to γ-rays.

Dosimetric characterization of silicon and diamond detectors in low-energy proton beams.

The dosimetric behaviour of a Scanditronix p-type silicon diode and a PTW natural diamond detector was studied in low-energy proton beams in the 8.3-21.5 MeV range. The properties investigated were linearity, reproducibility, dose rate dependence, energy and linear energy transfer (LET) dependence. The influence of detector thickness on the results of depth dose measurements was also demonstrated. A Markus parallel plate ionization chamber was used for reference dosimetry. Silicon diode and diamond detectors showed linearity at therapeutic dose level, reproducibility better than 1% (1sigma) and sensitivity variation with dose rate and proton energy.

Charged particle’s flux measurement from PMMA irradiated by 80 MeV/u carbon ion beam

Hadrontherapy is an emerging technique in cancer therapy that uses beams of charged particles. To meet the improved capability of hadrontherapy in matching the dose release with the cancer position, new dose-monitoring techniques need to be developed and introduced into clinical use. The measurement of the fluxes of the secondary particles produced by the hadron beam is of fundamental importance in the design of any dose-monitoring device and is eagerly needed to tune Monte Carlo simulations. We report the measurements carried out with charged secondary particles produced from the interaction of a 80 MeV/u fully stripped carbon ion beam at the INFN Laboratori Nazionali del Sud, Catania, with a poly-methyl methacrylate target. Charged secondary particles, produced at 90° with respect to the beam axis, have been tracked with a drift chamber, while their energy and time of flight have been measured by means of a LYSO scintillator. Secondary protons have been identified exploiting the energy and time-of-flight information, and their emission region has been reconstructed backtracking from the drift chamber to the target. Moreover, a position scan of the target indicates that the reconstructed emission region follows the movement of the expected Bragg peak position. Exploiting the reconstruction of the emission region, an accuracy on the Bragg peak determination in the submillimeter range has been obtained. The measured differential production rate for protons produced with E(Prod)(kin) > 83 MeV and emitted at 90° with respect to the beam line is dN(P)/(dN(C)dΩ) (E(Prod)(kin) > 83 MeV, θ = 90°) = (2.69 ± 0.08(stat) ± 0.12(sys)) × 10⁻⁴ sr⁻¹.