(1) Background: Radioprotective agents have garnered considerable interest due to their prospective applications in radiotherapy, public health medicine, and situations of large-scale accidental ...radiation exposure or impending radiological emergencies. Cystamine, an organic diamino-disulfide compound, is recognized for its radiation-protective and antioxidant properties. This study aims to utilize the aqueous ferrous sulfate (Fricke) dosimeter to measure the free-radical scavenging capabilities of cystamine during irradiation by fast carbon ions. This analysis spans an energy range from 6 to 500 MeV per nucleon, which correlates with "linear energy transfer" (LET) values ranging from approximately 248 keV/μm down to 9.3 keV/μm. (2) Methods: Monte Carlo track chemistry calculations were used to simulate the radiation-induced chemistry of aerated Fricke-cystamine solutions across a broad spectrum of cystamine concentrations, ranging from 10
to 1 M. (3) Results: In irradiated Fricke solutions containing cystamine, cystamine is observed to hinder the oxidation of Fe
ions, an effect triggered by oxidizing agents from the radiolysis of acidic water, resulting in reduced Fe
ion production. Our simulations, conducted both with and without accounting for the multiple ionization of water, confirm cystamine's ability to capture free radicals, highlighting its strong antioxidant properties. Aligning with prior research, our simulations also indicate that the protective and antioxidant efficiency of cystamine diminishes with increasing LET of the radiation. This result can be attributed to the changes in the geometry of the track structures when transitioning from lower to higher LETs. (4) Conclusions: If we can apply these fundamental research findings to biological systems at a physiological pH, the use of cystamine alongside carbon-ion hadrontherapy could present a promising approach to further improve the therapeutic ratio in cancer treatments.
Chondrosarcoma is a malignant cartilaginous tumor that is particularly chemoresistant and radioresistant to X-rays. The first line of treatment is surgery, though this is almost impossible in some ...specific locations. Such resistances can be explained by the particular composition of the tumor, which develops within a dense cartilaginous matrix, producing a resistant area where the oxygen tension is very low. This microenvironment forces the cells to adapt and dedifferentiate into cancer stem cells, which are described to be more resistant to conventional treatments. One of the main avenues considered to treat this type of tumor is hadrontherapy, in particular for its ballistic properties but also its greater biological effectiveness against tumor cells. In this review, we describe the different forms of chondrosarcoma resistance and how hadrontherapy, combined with other treatments involving targeted inhibitors, could help to better treat high-grade chondrosarcoma.
This investigation focused on the characterization of the lateral dose fall-off following the irradiation of the target with photons, protons and carbon ions. A water phantom was irradiated with a ...rectangular field using photons, passively delivered protons as well as scanned protons and carbon ions. The lateral dose profile in the depth of the maximum dose was measured using an ion chamber, a diamond detector and thermoluminescence detectors TLD-600 and TLD-700. The yield of thermal neutrons was estimated for all radiation types while their complete spectrum was measured with bubble detectors during the irradiation with photons. The peripheral dose delivered by photons is significantly higher compared to both protons and carbon ions and exceeds the latter by up to two orders of magnitude at distances greater than 50 mm from the field. The comparison of passive and active delivery techniques for protons shows that, for the chosen rectangular target shape, the former has a sharper penumbra whereas the latter has a lower dose in the far-out-of-field region. When comparing scanning treatments, carbon ions present a sharper dose fall-off than protons close to the target but increasing peripheral dose with increasing incident energy. For photon irradiation, the contribution to the out-of-field dose of photoneutrons appears to be of the same order of magnitude as the scattered primary beam. Charged particles show a clear supremacy over x-rays in achieving a higher dose conformality around the target and in sparing the healthy tissue from unnecessary radiation exposure. The out-of-field dose for x-rays increases with increasing beam energy because of the production of biologically harmful neutrons.
The goal of the FOOT (FragmentatiOn Of Target) experiment is to measure the fragmentation cross section of protons into H, C, O targets at beam energies of interest for hadrontherapy (50–250 MeV for ...protons and 50–400 MeV/u for Carbon ions) (Tommasino et al., 2015 1; FOOT CDR Conceptual Design, 0000 2). Given the short range of the fragments, an inverse kinematic approach has been chosen, hence requiring precise tracking capabilities for charged ions. One of the foreseen experiment subsystems will be the MSD (Microstrip Silicon Detector), composed of three x–y measuring planes. In this work we evaluate the suitability of standard double-sided microstrip detectors, coupled to an high dynamic range readout chip, to be used for this task. The results about cluster signal, signal/noise, and dynamic range of readout chip are encouraging, and confirm the suitability of this class of sensors to be used in the FOOT experiment.
We investigate, by means of Geant4 simulations, a real-time method to control the position of the Bragg peak during ion therapy, based on a Compton camera in combination with a beam tagging device ...(hodoscope) in order to detect the prompt gamma emitted during nuclear fragmentation. The proposed set-up consists of a stack of 2
mm thick silicon strip detectors and a LYSO absorber detector. The
γ
emission points are reconstructed analytically by intersecting the ion trajectories given by the beam hodoscope and the Compton cones given by the camera. The camera response to a polychromatic point source in air is analyzed with regard to both spatial resolution and detection efficiency. Various geometrical configurations of the camera have been tested. In the proposed configuration, for a typical polychromatic photon point source, the spatial resolution of the camera is about 8.3
mm FWHM and the detection efficiency 2.5×10
−4 (reconstructable photons/emitted photons in
4
π
). Finally, the clinical applicability of our system is considered and possible starting points for further developments of a prototype are discussed.
The intrinsic electronic properties of diamond make it suitable for radiation-hard and very fast detector development with good signal to noise ratios. With the advent of new generations of ion ...accelerators either for physics (nuclear and high energy physics) or medical applications (hadrontherapy and synchrotron radiation radiotherapy) there is a need for a very accurate beam monitoring in high radiation environments. Diamond is particularly suited to these applications. Fast pulse detection mode for time stamp, and current integration mode for operation as beam monitors at high particle rates are targeted. Commercial single-crystal, polycrystalline and heteroepitaxial diamonds produced by Chemical Vapor Deposited (CVD) method are analyzed and compared by means of X-ray Beam Induced Current (XBIC). Their performance as particle detectors is investigated using a 8.5 keV X-ray photon micro-bunch beam at ESRF (European Synchrotron Radiation Facility). This facility provides a focused (~1 μm) pulsed beam (100 ps bunch duration), producing an almost uniform energy deposit along the beam irradiated volume in the detector, therefore closely mimicking the interaction of single charged particles. The XBIC set-up of the ID21 beamline enabled us to draw 2D response maps of detectors with disk- and strip metal contact patterns. Using the pulse-synchronized XBIC measurements, a time resolution of 150 ps RMS and bunch detection efficiency of ~100% were evaluated at the contact strip crossing points of a first prototype polycrystalline beam monitor.
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•Diamond double stripped beam monitor prototypes for hadrontherapy monitoring.•Chemical Vapor Deposited diamond detector performance evaluated under X-rays.•2D current maps evaluated on diamond metallized surface using X-rays micro beams.•Time resolution and bunch detection efficiency at contact strip crossing points.
The interaction of the incoming beam radiation with the patient body in hadrontherapy treatments produces secondary charged and neutral particles, whose detection can be used for monitoring purposes ...and to perform an on-line check of beam particle range. In the context of ion-therapy with active scanning, charged particles are potentially attractive since they can be easily tracked with a high efficiency, in presence of a relatively low background contamination. In order to verify the possibility of exploiting this approach for in-beam monitoring in ion-therapy, and to guide the design of specific detectors, both simulations and experimental tests are being performed with ion beams impinging on simple homogeneous tissue-like targets (PMMA). From these studies, a resolution of the order of few millimeters on the single track has been proven to be sufficient to exploit charged particle tracking for monitoring purposes, preserving the precision achievable on longitudinal shape. The results obtained so far show that the measurement of charged particles can be successfully implemented in a technology capable of monitoring both the dose profile and the position of the Bragg peak inside the target and finally lead to the design of a novel profile detector. Crucial aspects to be considered are the detector positioning, to be optimized in order to maximize the available statistics, and the capability of accounting for the multiple scattering interactions undergone by the charged fragments along their exit path from the patient body. The experimental results collected up to now are also valuable for the validation of Monte Carlo simulation software tools and their implementation in Treatment Planning Software packages.
The use of protons and heavy ions for the treatment of tumors is increasing since it provides a better relative biological effectiveness (RBE) than traditional radiotherapy. Accurate knowledge of the ...energy deposition at submicrometric scales is paramount for RBE characterization. This paper shows the latest version of the silicon cylindrical microdosimeter array developed by the Instituto de Microelectrónica de Barcelona, Centro Nacional de Microelectrónica (IMB-CNM, Spain). The detector consists of a matrix of <inline-formula> <tex-math notation="LaTeX">11 \times 11 </tex-math></inline-formula> cylindrical sensitive unit cells with individual readout etched within the silicon substrate available in different diameters and pitches between detectors. The detector employed in this paper had a diameter of <inline-formula> <tex-math notation="LaTeX">15~\mu \text{m} </tex-math></inline-formula>, a pitch of <inline-formula> <tex-math notation="LaTeX">200~\mu \text{m} </tex-math></inline-formula>, and a thickness of <inline-formula> <tex-math notation="LaTeX">5.5~\mu \text{m} </tex-math></inline-formula>. The detectors were tested in the clinical facilities of Fondazione Centro Nazionale di Adronterapia Oncologica (CNAO) (Pavia, Italy) employing a 12 C pencil beam at a therapeutic beam fluence rate. Microdosimetric spectra of lineal energy were measured in different depths of polymethyl methacrylate (PMMA) up to the Bragg peak. Results were then compared with Monte Carlo simulations using the FLUKA particle transport code, showing an excellent agreement between experimental and simulated microdosimetric distributions even at the high fluence rates associated with clinical beams.
From surviving fraction to tumour curability, definitions of tumour radioresistance may vary depending on the view angle. Yet, mechanisms of radioresistance have been identified and involve ...tumour-specific oncogenic signalling pathways, tumour metabolism and proliferation, tumour microenvironment/hypoxia, genomics. Correlations between tumour biology (histology) and imaging allow theragnostic approaches that use non-invasive biological imaging using tracer functionalization of tumour pathway biomarkers, imaging of hypoxia, etc. Modelling dose prescription function based on their tumour radio-resistant factor enhancement ratio, related to metabolism, proliferation, hypoxia is an area of investigation. Yet, the delivery of dose painting by numbers/voxel-based radiotherapy with low lineal energy transfer particles may be limited by the degree of modulation complexity needed to achieve the doses needed to counteract radioresistance. Higher lineal energy transfer particles or combinations of different particles, or combinations with drugs and devices such as done with radioenhancing nanoparticles may be promising.
Si les définitions de la radiorésistance des tumeurs peuvent varier selon l’angle de vue, radiobiologique ou clinique, les mécanismes de la radiorésistance sont partiellement identifiés. Ils impliquent des voies de signalisation oncogènes spécifiques aux tumeurs, le métabolisme et la prolifération des tumeurs, le microenvironnement tumoral/hypoxie, et peuvent reposer sur une génomique somatique spécifique. Les corrélations entre la biologie des tumeurs (histologie) et l’imagerie permettent des approches théragnostiques qui utilisent une imagerie biologique non invasive (fonctionnalisation de traceurs des biomarqueurs des voies tumorales, imagerie de l’hypoxie, etc). La modélisation de la fonction de prescription des doses en fonction de leur rapport d’amélioration d’un facteur de radiorésistance des tumeurs, lié au métabolisme, à la prolifération, à l’hypoxie est un domaine en cours d’investigations. Pourtant, la délivrance d’une irradiation très modulée, voxel par voxel, avec des particules à faible transfert d’énergie linéal, peut être limitée par le degré de complexité de la modulation nécessaire pour obtenir les doses requises pour contrer la radiorésistance tumorale. Des particules à transfert d’énergie linéal plus élevé ou des combinaisons de différentes particules, ou des combinaisons avec des médicaments et dispositifs comme celles réalisées avec des nanoparticules améliorant la radioprotection peuvent être envisagées.
The FragmentatiOn mymargin Of Target (FOOT) experiment aims to provide precise nuclear cross section measurements for two different fields: hadrontherapy and radio-protection in space. The main ...reason is the important role the nuclear fragmentation process plays in both fields, where the health risks caused by radiation are very similar and mainly attributable to the fragmentation process. The FOOT experiment has been developed in such a way that the experimental setup is easily movable and fits the space limitations of the experimental and treatment rooms available in hadrontherapy treatment centers, where most of the data takings are carried out. The trigger and data acquisition system needs to follow the same criteria and it should work in different laboratories and different conditions. It has been designed to acquire high statistics samples to fulfill the accuracy requirements of the physics analysis. Data-taking is being monitored online to allow the shift crew to verify the correct functioning of the system.
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