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El texto completo de este trabajo no se encuentra disponible por no haber sido facilitado aún por su autor, por restricciones de copyright, o por no existir una versión digital, Passive dosimetry with radiochromic films is widely used in proton radiotherapy, both in clinical and scientific environments, thanks to its simplicity, high spatial resolution and dose-rate independence. However, film under-response for low-energy protons, the so-called linear-energy transfer (LET) quenching, must be accounted and corrected for. We perform a meta-analysis on existing film under-response data with EBT, EBT2 and EBT3 GAFchromic (TM) films and provide a common framework to integrate it, based on the calculation of dose-averaged LET in the active layer of the films. We also report on direct measurements with the 10 MeV proton beam at the Center for Microanalysis of Materials (CMAM) for EBT2, EBT3 and unlaminated EBT3 films, focusing on the 20-80 keV mu m(-1) LET range, where previous data was scarce. Measured film relative efficiency (RE) values are in agreement with previously reported data from the literature. A model on film RE constructed with combined literature and own experimental values in the 5-80 keV mu m(-1) LET range is presented, supporting the hypothesis of a linear decrease of RE with LET, with no remarkable differences between the three types of films analyzed., Comunidad de Madrid, Ministerio de Ciencia e Innovación (España), European Regional Funds, Union Europea. H2020, Universidad Complutense de Madrid, Instituto de Salud Carlos III, Pro CNIC Foundation, Centros de Excelencia Severo Ochoa, Depto. de Estructura de la Materia, Física Térmica y Electrónica, Fac. de Ciencias Físicas, TRUE, pub

This work was funded by Comunidad de Madrid under project B2017/BMD-3888 PRONTO-CM “Protontherapy and nuclear techniques for oncology” and by the Spanish Government and EU Regional Funds (RTI2018-098868-B-I00, RTC-2015-3772-1). A. Espinosa Rodríguez has been funded by a FPU predoctoral fellowship of the Spanish Ministerio de Educación, Cultura y Deporte (FPU18/02551). This is a contribution for the Moncloa Campus of International Excellence, “Grupo de Física Nuclear-UCM”, Ref. 910059. Part of the calculations of this work were performed in the “Clúster de Cálculo para Técnicas Físicas”, funded in part by Universidad Complutense de Madrid and in part by EU Regional Funds., BackgroundRecent proposals of high dose rate plans in protontherapy as well as very short proton bunches may pose problems to current beam monitor systems. There is an increasing demand for real-time proton beam monitoring with high temporal resolution, extended dynamic range and radiation hardness. Plastic scintillators coupled to optical fiber sensors have great potential in this context to become a practical solution towards clinical implementation. PurposeIn this work, we evaluate the capabilities of a very compact fast plastic scintillator with an optical fiber readout by a SiPM and electronics sensor which has been used to provide information on the time structure at the nanosecond level of a clinical proton beam. Materials and methodsA 3 x 3 x 3 mm(3) plastic scintillator (EJ-232Q Eljen Technology) coupled to a 3 x 3 mm(2) SiPM (MicroFJ-SMA-30035, Onsemi) has been characterized with a 70 MeV clinical proton beam accelerated in a Proteus One synchrocyclotron. The signal was read out by a high sampling rate oscilloscope (5 GS/s). By exposing the sensor directly to the proton beam, the time beam profile of individual spots was recorded. ResultsMeasurements of detector signal have been obtained with a time sampling period of 0.8 ns. Proton bunch period (16 ns), spot (10 mu s) and interspot (1 ms) time structures could be observed in the time profile of the detector signal amplitude. From this, the RF frequency of the accelerator has been extracted, which is found to be 64 MHz. ConclusionsThe proposed system was able to measure the fine time structure of a clinical proton accelerator online and with ns time resolution., Comunidad de Madrid, Gobierno de España, EU Regional Funds, Ministerio de Educación, Cultura y Deporte, Depto. de Estructura de la Materia, Física Térmica y Electrónica, Fac. de Ciencias Físicas, TRUE, pub

This work was funded by Comunidad de Madrid under project B2017/BMD-3888 PRONTO-CM "Protontherapy and nuclear techniques for oncology". Support by the Spanish Government (RTI 2018-098868-B-I00, RTC-2015-3772-1, XPHASE-LASER, CPP 2021-008751 NEW-MBI) , as well as European Regional and Resilience Funds, and the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 793576 (CAP-PERAM) is acknowledged. This is a contribution for the Moncloa Campus of International Excellence, "Grupo de Física Nuclear-UCM", Ref. 910059. Part of the calculations of this work were performed in the "Cluster de Calculo para Técnicas Físicas", funded in part by UCM and in part by EU Regional Funds., We propose a new concept of small animal X-ray irradiator based on a conventional imaging X-ray tube for preclinical research. In this work we assessed its feasibility to deliver FLASH dose rates. Our design puts the imaging X-ray tube into a shielded cabinet, which makes the system affordable and suitable to use without disruption in existing laboratories and with minimum regulatory burden. Two conventional 150 kVp X-ray tubes were characterized with Gafchromic films for dose rates and dose uniformity. Monte Carlo simulations were also performed to model the irradiator, and the efficiencies of the tube and dose rates (with and without additional filtration) were calculated and compared with measurements. The feasibility of achieving ultra-high dose rates was determined from the rating charts provided by the manufacturer and measurements. The small animal irradiator proposed in this work was able to deliver conventional dose rate irradiation (0.5-1 Gy/min) at 150 kVp at 20 cm distance with minimum amount of filtration. FLASH irradiations (a 10 Gy dose delivered at >40 Gy/s) were also possible at the maximum capabilities of the tubes by placing the samples at the closest possible distances from the sources. A first prototype has already been built and characterized., Comunidad de Madrid, Gobierno de España, European Regional and Resilience Funds, European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant, Moncloa Campus of International Excellence, "Grupo de Fisica Nuclear-UCM", Universidad Complutense de Madrid (UCM), EU Regional Funds, Depto. de Estructura de la Materia, Física Térmica y Electrónica, Fac. de Ciencias Físicas, TRUE, pub

Proton therapy allows the treatment of specific areas and avoids the surrounding tissues. However, this technique has uncertainties in terms of the distal dose fall-off. A promising approach to studying the proton range is the use of nanoparticles as proton-activatable agents that produce detectable signals. For this, we developed an iron oxide nanoparticle doped with Zn (IONP@Zn-cit) with a hydrodynamic size of 10 nm and stability in serum. Cytotoxicity, defined as half of the surveillance, was 100 μg Zn/mL in the U251 cell line. The effect on clonogenic cell death was tested after X-ray irradiation, which suggested a radioprotective effect of these nanoparticles at low concentrations (1–10 μg Zn/mL). To evaluate the production of positron emitters and prompt-gamma signals, IONP@Zn-cit was irradiated with protons, obtaining prompt-gamma signals at the lowest measured concentration (10 mg Zn/mL). Finally, 67Ga-IONP@Zn-cit showed accumulation in the liver and spleen and an accumulation in the tumor tissue of 0.95% ID/g in a mouse model of U251 cells. These results suggest the possibility of using Zn nanoparticles as proton-activatable agents to verify the range by prompt gamma detection and face the challenges of prompt gamma detection in a specific biological situation, opening different avenues to go forward in this field.

This work was funded by the Comunidad de Madrid under project B2017/BMD-3888 PRONTO-CM "Protontherapy and nuclear techniques for oncology" and by the Spanish Government and EU Regional Funds (RTI2018-098868-B-I00, RTC-2015-3772-1). A. Espinosa Rodríguez was funded by an FPU predoctoral fellowship of the Spanish Ministerio de Educación, Cultura y Deporte (FPU18/02551). This is a contribution for the Moncloa Campus of International Excellence, "Grupo de Física Nuclear-UCM", Ref. 910059. Part of the calculations of this work were performed in the "Cluster de Cálculo para Técnicas Físicas", funded in part by UCM and in part by EU Regional Funds., Ultra-high dose rate (UHDR) irradiation regimes have the potential to spare normal tissue while keeping equivalent tumoricidal capacity than conventional dose rate radiotherapy (CONV-RT). This has been called the FLASH effect. In this work, we present a new simulation framework aiming to study the production of radical species in water and biological media under different irradiation patterns. The chemical stage (heterogeneous phase) is based on a nonlinear reaction-diffusion model, implemented in GPU. After the first 1 mu s, no further radical diffusion is assumed, and radical evolution may be simulated over long periods of hundreds of seconds. Our approach was first validated against previous results in the literature and then employed to assess the influence of different temporal microstructures of dose deposition in the expected biological damage. The variation of the Normal Tissue Complication Probability (NTCP), assuming the model of Labarbe et al., where the integral of the peroxyl radical concentration over time (AUC-ROO) is taken as surrogate for biological damage, is presented for different intra-pulse dose rate and pulse frequency configurations, relevant in the clinical scenario. These simulations yield that overall, mean dose rate and the dose per pulse are the best predictors of biological effects at UHDR., Comunidad de Madrid, Gobierno de España, EU Regional Funds, FPU predoctoral fellowship of the Spanish Ministerio de Educación, Cultura y Deporte, Universidad Complutense de Madrid (UCM), EU Regional Funds, Depto. de Estructura de la Materia, Física Térmica y Electrónica, Fac. de Ciencias Físicas, TRUE, pub

This article was funded by Comunidad de Madrid (B2017/BMD-3888, 2017-T1/BMD-5468), European Union (793576), Spanish Government (SAF2016-76588-C2-1-R, RTI2018-098868-B-I00, RTI2018-098868-B-I00, BBVA, BBM-TRA-0041, BBM-TRA-0041)., Range verification of clinical protontherapy systems via positron-emission tomography (PET) is not a mature technology, suffering from two major issues: insufficient signal from low-energy protons in the Bragg peak area and biological washout of PET emitters. The use of contrast agents including O-18, Zn-68 or Cu-63, isotopes with a high cross section for low-energy protons in nuclear reactions producing PET emitters, has been proposed to enhance the PET signal in the last millimeters of the proton path. However, it remains a challenge to achieve sufficient concentrations of these isotopes in the target volume. Here we investigate the possibilities of O-18-enriched water (18-W), a potential contrast agent that could be incorporated in large proportions in live tissues by replacing regular water. We hypothesize that 18-W could also mitigate the problem of biological washout, as PET (F-18) isotopes created inside live cells would remain trapped in the form of fluoride anions (F-), allowing its signal to be detected even hours after irradiation. To test our hypothesis, we designed an experiment with two main goals: first, prove that 18-W can incorporate enough O-18 into a living organism to produce a detectable signal from F-18 after proton irradiation, and second, determine the amount of activity that remains trapped inside the cells. The experiment was performed on a chicken embryo chorioallantoic membrane tumor model of head and neck cancer. Seven eggs with visible tumors were infused with 18-W and irradiated with 8-MeV protons (range in water: 0.74 mm), equivalent to clinical protons at the end of particle range. The activity produced after irradiation was detected and quantified in a small-animal PET-CT scanner, and further studied by placing ex-vivo tumours in a gamma radiation detector. In the acquired images, specific activity of F-18 (originating from 18-W) could be detected in the tumour area of the alive chicken embryo up to 9 h after irradiation, which conf, Unión Europea, Ministerio de Ciencia, Innovación y Universidades (España), Comunidad de Madrid, Depto. de Estructura de la Materia, Física Térmica y Electrónica, Sección Deptal. de Bioquímica y Biología Molecular (Farmacia), Fac. de Ciencias Físicas, Fac. de Farmacia, TRUE, pub

Proyecto de innovación docente con el objetivo de desarrollar una herramienta que facilite el aprendizaje de las aplicaciones a la Medicina de la Física Nuclear. Se ha creado el sitio web https://fisnucmed.wordpress.com/. Se abordan, entre otros contenidos, las radiaciones ionizantes y los fundamentos de la interacción de la radiación con la materia, nociones de detección de radiación e instrumentación nuclear , diagnóstico por imagen, y las modalidades de imagen PET, SPECT, CT, resonancia magnética nuclear, ultrasonidos, así como la radioterapia y en particular la hadronterapia.