D. Moro

Towards the final BSA modeling for the accelerator-driven BNCT facility at INFN LNL.

Some remarkable advances have been made in the last years on the SPES-BNCT project of the Istituto Nazionale di Fisica Nucleare (INFN) towards the development of the accelerator-driven thermal neutron beam facility at the Legnaro National Laboratories (LNL), aimed at the BNCT experimental treatment of extended skin melanoma. The compact neutron source will be produced via the (9)Be(p,xn) reactions using the 5 MeV, 30 mA beam driven by the RFQ accelerator, whose modules construction has been recently completed, into a thick beryllium target prototype already available. The Beam Shaping Assembly (BSA) final modeling, using both neutron converter and the new, detailed, Be(p,xn) neutron yield spectra at 5 MeV energy recently measured at the CN Van de Graaff accelerator at LNL, is summarized here.

Tumor-localizing and radiosensitizing properties of meso-tetra(4-nido-carboranylphenyl)porphyrin (H2TCP)

Background and Purpose: Boron Neutron Capture Therapy (BNCT) is a binary cancer treatment that exploits the short range particles released from a nuclear fission reaction involving the non-radioactive 10B nucleus and low-energy neutrons for the destruction of tumor cells. In this perspective, porphyrins and phthalocyanines can represent a vehicle for the transport of significant amounts of boron to the neoplastic lesion. Material and Methods: B16F1 melanotic melanoma subcutaneously transplanted in C57/BL6 mice has been used as an in vivo model. Pharmacokinetic studies were performed by intratumoral and intravenous injection of a meso-substituted porphyrin containing 36 B atoms per molecule (H2TCP) and the distribution of H2TCP in the tumor was assessed by fluorescence microscopy analysis. The tumor-bearing mice were exposed to the radiation field for 20 min at a reactor power of 5 kW. Results: At 0.5 h after intratumoral administration or at 24 h after intravenous injection, the amount of 10B in the tumor was found to be about 60 ppm and about 6 ppm, respectively. In spite of the different amounts of 10B in the tumor at the time of irradiation, a very similar delay in tumor growth (5-6 days) was induced by neutron irradiation in the two groups of injected mice with respect to control mice. Conclusions: Our results demonstrate that a suitable boron-loaded porphyrin displays a significant affinity for subcutaneous tumors, and upon activation by thermal neutrons, can promote an important response even in a fairly aggressive and generally radioresistant tumor such as melanotic melanoma.

Equivalence of pure propane and propane TE gases for microdosimetric measurements

A tissue-equivalent proportional counter (TEPC) simulates micrometric volumes of tissue if the energy deposited in the counter cavity is the same as that in the tissue volume. Nevertheless, a TEPC measures only the ionisations created in the gas, which are later converted into imparted energy. Therefore, the equivalence of the simulated diameter (Dρ) in two gases should be based on the equality of the mean number of ions pairs in the gas rather than on the imparted energy. Propane-based tissue-equivalent gas is the most commonly used gas mixture at present, but it has the drawback that its composition may change with time. From this point of view, the use of pure propane offers practical advantages: higher gas gain and longer stability. In this work, microdosimetric measurements performed with pure propane, at site sizes 0.05 mg cm(-2) ≤ Dρ ≤ 0.3 mg cm(-2), demonstrate that the response of a propane-filled detector in gamma and in neutron fields is almost the same if an appropriate gas density is used.

Lineal energy calibration of a spherical TEPC

Tissue-equivalent proportional counters (TEPCs) do not always allow built-in calibration alpha-particle sources, and the lineal energy calibration of these counters must be performed with an external radiation able to penetrate the detector walls. The irradiation field can be used for calibration if a particular marker point of known lineal energy is identified in the measured spectrum. This point is often identified with the proton edge, which corresponds to the maximum energy deposited by protons in the given volume. If the proton edge cannot be identified precisely in the measured spectrum, a gamma source can be used instead, identifying the maximum lineal energy due to electrons (e-edge). The technique was already described and applied for cylindrical TEPCs, allowing a calibration with an overall uncertainty smaller than 5 % (Conte et al. Lineal energy calibration of mini tissue equivalent gas-proportional counters (TEPC). AIP Conf. Proc. 1530, 171-178 (2013)). In the present work, this study was repeated for spherical detectors. First a marker point was identified in the microdosimetric spectrum of a (137)Cs gamma source, then a precise value of lineal energy was assigned to it. Gas pressures were varied to simulate diameters from 0.5 and 3 µm at density 1 g cm(-3). A simple power equation is given for allowing calibration of TEPCs filled with C3H8-TE gas at different pressures, using an external (137)Cs gamma source.

BNCT dosimetry performed with a mini twin tissue-equivalent proportional counters (TEPC)

The BNCT radiation field is complex because different beam components are mixed, each one having different relative biological effectiveness (RBE). Microdosimetry with tissue-equivalent proportional counters (TEPC) has proven to be an ideal dosimetric technique for mixed radiation fields, because it is able both to measure the absorbed dose and to assess the radiation field relative biological effectiveness with good accuracy. An ideal detector for BNCT should contain two TEPCs, one detector loaded with, while the other one without (10)B in order to record all beam components with a unique measurement. Moreover, such a detector should be of tiny size in order to be able to measure in the intense BNCT radiation fields without significant pile-up effects. TEPCs have been shown to be pretty good dosimeters for mixed radiation fields. In this paper the first mini twin TEPC counter for BNCT is presented, as well as first measurement at the new HYTHOR thermal irradiation facility at TAPIRO nuclear reactor and comparison with related Monte Carlo calculations.

Nanodosimetric descriptors of the radiation quality of carbon ions

In view of the emerging interest of carbon ions in radiotherapy and of the strong correlation between the track structure and the radiobiological effectiveness of ionising radiations, the track-structure properties of (12)C-ions were studied at particle energies close to the Bragg peak. To perform the investigations, ionisation-cluster-size distributions for nanometre-sized target volumes were measured with the track-nanodosimeter installed at the TANDEM-ALPI accelerator complex at LNL, and calculated using a dedicated Monte Carlo simulation code. The resulting cluster-size distributions are used to derive particular descriptors of particle track structure. Here, the main emphasis is laid on the mean ionisation-cluster size M1 and the cumulative probability Fk of measuring cluster sizes ν ≥ k. From the radiobiological point of view, Fk is of particular interest because an increasing k corresponds to an increase of damages of higher complexity. In addition, Fk saturates with increasing radiation quality like radiobiological cross sections as a function of linear energy transfer. Results will be presented and discussed for (12)C-ions at 96 and 240 MeV.

TEPC gas gain measurements in propane

Knowledge of the gas gain is important to optimise the design and the operating characteristics of tissue-equivalent proportional counters (TEPCs), especially for simulated sites smaller than 1 µm. TEPC area monitors of the order of centimetres must operate at very low gas pressure to simulate micrometric volumes, consequently the Townsend theory cannot be applied: effects related to the presence of an electric-field gradient become important and must be considered. A detailed description of the electron avalanche formation is complex, but in most practical cases an analytical formula can be used. The so-called gradient-field model includes three characteristic constants of the counting gas, which were already experimentally determined for propane-tissue equivalent (TE) and dimethyl ether (DME) gases. The aim of this work is to measure the gas-dependent parameters for propane gas. Preliminary results obtained with a spherical TEPC are presented.

Influence of the physical data to calibrate TEPCs

Tissue-equivalent proportional counters (TEPCs) measure distributions of ionisations, produced in the gas cavity by the radiation field which are afterwards converted into distributions of energy imparted by applying a calibration factor. To calibrate the pulse-height spectra, first, a marker point must be identified in the measured spectrum. Then, an accurate value of lineal energy must be assigned to this marker. A common marker that is often used for calibration is the so-called proton-edge (p-edge). It is a distinctive feature of a proton or neutron spectrum which corresponds to the maximum amount of energy that a proton can deposit in the active volume of the detector. A precise method to identify the marker point was applied to identify the p-edge with an uncertainty below 1 %. To evaluate the final uncertainty of the calibration, the uncertainty of the energy value assigned to the p-edge must also be considered. This value can be evaluated using different energy-range tables. This study investigates how the choice of different input databases for calibration purposes influences the calibration. The effect of three different frequently used sets of input data was analysed for pure propane gas and for propane-TE gas mixture.

Nanodosimetric track structure in homogeneous extended beams

Physical aspects of particle track structure are important in determining the induction of clustered damage in relevant subcellular structures like the DNA and higher-order genomic structures. The direct measurement of track-structure properties of ionising radiation is feasible today by counting the number of ionisations produced inside a small gas volume. In particular, the so-called track-nanodosimeter, installed at the TANDEM-ALPI accelerator complex of LNL, measures ionisation cluster-size distributions in a simulated subcellular structure of dimensions 20 nm, corresponding approximately to the diameter of the chromatin fibre. The target volume is irradiated by pencil beams of primary particles passing at specified impact parameter. To directly relate these measured track-structure data to radiobiological measurements performed in broad homogeneous particle beams, these data can be integrated over the impact parameter. This procedure was successfully applied to 240 MeV carbon ions and compared with Monte Carlo simulations for extended fields.

Progress on the accelerator based SPES‐BNCT project at INFN Legnaro

In the framework of an advanced Exotic Ion Beam facility, named SPES (Study and Production of Exotic Species), that will allow a frontier program both in nuclear and interdisciplinary physics, an intense thermal neutron beam facility, devoted to perform Boron Neutron Capture Therapy (BNCT) experimental treatments on skin melanoma tumor, is currently under construction based on the SPES proton driver. A vast radiobiological investigation in vitro and in vivo has started with the new 10B carriers developed. Special microdosimetric detectors have been constructed to properly measure all the BNCT dose components and their qualities. Both microdosimetric and radiobiological measurements are being performed at the new HYTHOR beam shaping assembly at the Enea‐Casaccia TAPIRO reactor.