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BACKGROUND: Phenomenological relative biological effectiveness (RBE) models for proton therapy, based on the dose-averaged linear energy transfer (LET), have been developed to address the apparent RBE increase towards the end of the proton range. The results of these phenomenological models substantially differ due to varying empirical assumptions and fitting functions. In contrast, more theory-based approaches are used in carbon ion radiotherapy, such as the microdosimetric kinetic model (MKM). However, implementing microdosimetry-based models in LET-based proton therapy treatment planning systems poses challenges. PURPOSE: This work presents a LET-based version of the MKM that is practical for clinical use in proton radiotherapy. METHODS: At first, we derived an approximation of the Mayo Clinic Florida (MCF) MKM for relatively-sparsely ionizing radiation such as protons. The mathematical formalism of the proposed model is equivalent to the original MKM, but it maintains some key features of the MCF MKM, such as the determination of model parameters from measurable cell characteristics. Subsequently, we carried out Monte Carlo calculations with PHITS in different simulated scenarios to establish a heuristic correlation between microdosimetric quantities and the dose averaged LET of protons. RESULTS: A simple allometric function was found able to describe the relationship between the dose-averaged LET of protons and the dose-mean lineal energy, which includes the contributions of secondary particles. The LET-based MKM was used to model the in vitro clonogenic survival RBE of five human and rodent cell lines (A549, AG01522, CHO, T98G, and U87) exposed to pristine and spread-out Bragg peak (SOBP) proton beams. The results of the LET-based MKM agree well with the biological data in a comparable or better way with respect to the other models included in the study. A sensitivity analysis on the model results was also performed. CONCLUSIONS: The LET-based MKM integrates the predictive theoretical framework of the MCF MKM with a straightforward mathematical description of the RBE based on the dose-averaged LET, a physical quantity readily available in modern treatment planning systems for proton therapy.
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Boron neutron capture therapy (BNCT) is a unique radiotherapy of selectively eradicating tumor cells using boron compounds (e.g., 4-borono-L-phenylalanine [BPA]) that are heterogeneously taken up at the cellular level. Such heterogenicity potentially reduces the curative efficiency. However, the effects of temporospatial heterogenicity on cell killing remain unclear. With the technical combination of radiation track detector and biophysical simulations, this study revealed the cell cycle-dependent heterogenicity of BPA uptake and subsequent biological effects of BNCT on HeLa cells expressing fluorescent ubiquitination-based cell cycle indicators, as well as the modification effects of polyvinyl alcohol (PVA). The results showed that the BPA concentration in the S/G2/M phase was higher than that in the G1/S phase and that PVA enhances the biological effects both by improving the uptake and by canceling the heterogenicity. These findings might contribute to a maximization of therapeutic efficacy when BNCT is combined with PVA and/or cell cycle-specific anticancer agents.
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Compuestos de Boro , Terapia por Captura de Neutrón de Boro , Ciclo Celular , Alcohol Polivinílico , Humanos , Terapia por Captura de Neutrón de Boro/métodos , Células HeLa , Alcohol Polivinílico/química , Ciclo Celular/efectos de la radiación , Ciclo Celular/efectos de los fármacos , Compuestos de Boro/farmacología , Fenilalanina/análogos & derivados , Fenilalanina/farmacologíaRESUMEN
In the next decade, the International Commission on Radiological Protection (ICRP) will issue the next set of general recommendations, for which evaluation of relative biological effectiveness (RBE) for various types of tissue reactions would be needed. ICRP has recently classified diseases of the circulatory system (DCS) as a tissue reaction, but has not recommended RBE for DCS. We therefore evaluated the mean and uncertainty of RBE for DCS by applying a microdosimetric kinetic model specialized for RBE estimation of tissue reactions. For this purpose, we analyzed several RBE data for DCS determined by past animal experiments and evaluated the radius of the subnuclear domain best fit to each experiment as a single free parameter included in the model. Our analysis suggested that RBE for DCS tends to be lower than that for skin reactions, and their difference was borderline significant due to large variances of the evaluated parameters. We also found that RBE for DCS following mono-energetic neutron irradiation of the human body is much lower than that for skin reactions, particularly at the thermal energy and around 1 MeV. This tendency is considered attributable not only to the intrinsic difference of neutron RBE between skin reactions and DCS but also to the difference in the contributions of secondary γ-rays to the total absorbed doses between their target organs. These findings will help determine RBE by ICRP for preventing tissue reactions.
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Radiometría , Efectividad Biológica Relativa , Humanos , Animales , Relación Dosis-Respuesta en la Radiación , Piel/efectos de la radiaciónRESUMEN
The knowledge on responses of human lens epithelial cells (HLECs) to ionizing radiation exposure is important to understand mechanisms of radiation cataracts that are of concern in the field of radiation protection and radiation therapy. However, biological effects in HLECs following protracted exposure have not yet fully been explored. Here, we investigated the temporal kinetics of γ-H2AX foci as a marker for DNA double-strand breaks (DSBs) and cell survival in HLECs after exposure to photon beams at various dose rates (i.e., 150 kVp X-rays at 1.82, 0.1, and 0.033 Gy/min, and 137Cs γ-rays at 0.00461 Gy/min (27.7 cGy/h) and 0.00081 Gy/min (4.9 cGy/h)), compared to those in human lung fibroblasts (WI-38). In parallel, we quantified the recovery for DSBs and cell survival using a biophysical model. The study revealed that HLECs have a lower DSB repair rate than WI-38 cells. There is no significant impact of dose rate on cell survival in both cell lines in the dose-rate range of 0.033-1.82 Gy/min. In contrast, the experimental residual γ-H2AX foci showed inverse dose rate effects (IDREs) compared to the model prediction, highlighting the importance of the IDREs in evaluating radiation effects on the ocular lens.
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Supervivencia Celular , Roturas del ADN de Doble Cadena , Relación Dosis-Respuesta en la Radiación , Células Epiteliales , Histonas , Cristalino , Humanos , Células Epiteliales/efectos de la radiación , Células Epiteliales/metabolismo , Cristalino/efectos de la radiación , Cristalino/citología , Roturas del ADN de Doble Cadena/efectos de la radiación , Histonas/metabolismo , Supervivencia Celular/efectos de la radiación , Radiación Ionizante , Línea Celular , Reparación del ADN/efectos de la radiación , Fibroblastos/efectos de la radiación , Fibroblastos/metabolismo , Rayos X , Rayos gamma/efectos adversosRESUMEN
Dose-averaged linear energy transfer (LETd) is conventionally evaluated from the relative biological effectiveness (RBE)-LETd fitted function used in the treatment planning system. In this study, we calculated the physical doses and their linear energy transfer (LET) distributions for patterns of typical CIRT beams using Monte Carlo (MC) simulation. The LETd was then deduced from the MC simulation and compared with that obtained from the conventional method. The two types of LETd agreed well with each other, except around the distal end of the spread-out Bragg peak. Furthermore, an MC simulation was conducted with the material composition of water and realistic materials. The profiles of physical dose and LETd were in good agreement for both techniques. These results indicate that the previous studies to analyze the minimum LETd in CIRT cases are valid for practical situations, and the material composition conversion to water little affects the dose distribution in the irradiation field.
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Radioterapia de Iones Pesados , Transferencia Lineal de Energía , Método de Montecarlo , Dosificación Radioterapéutica , Dosis de Radiación , Planificación de la Radioterapia Asistida por Computador/métodos , Agua/químicaRESUMEN
Previously, we have developed DynamicMC for modeling relative movement of Oak Ridge National Laboratory phantom in a radiation field for the Monte Carlo N-Particle package (Health Physics. 2023,124(4):301-309). Using this software, three-dimensional dose distributions in a phantom irradiated by a certain mono-energetic (Mono E) source can be deduced through its graphical user interface. In this study, we extended DynamicMC to be used in combination with the Particle and Heavy Ion Transport code System (PHITS) by providing it with a higher flexibility for dynamic movement for an anthropomorphic phantom. For this purpose, we implemented four new functions into the software, which are (1) to generate not only Mono E sources but also those having an energy spectrum of an arbitrary radioisotope (2) to calculate the absorbed doses for several radiologically important organs (3) to automatically average the calculated absorbed doses along the path of the phantom and (4) to generate user-defined slab shielding materials. The first and third items utilize the PHITS-specific modalities named radioisotope-source and sumtally functions, respectively. The computational cost and complexity can be dramatically reduced with these features. We anticipate that the present work and the developed open-source tools will be in the interest of nuclear radiation physics community for research and teaching purposes.
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Física Sanitaria , Radiometría , Radiometría/métodos , Física Sanitaria/métodos , Programas Informáticos , Movimiento , Fantasmas de Imagen , Radioisótopos , Método de MontecarloRESUMEN
The International Partner Agencies of the International Space Station (ISS) present a comparison of the ionizing radiation absorbed dose and risk quantities used to characterize example missions in lunar space. This effort builds on previous collaborative work that characterizes radiation environments in space to support radiation protection for human spaceflight on ISS in low-Earth orbit (LEO) and exploration missions beyond (BLEO). A "shielded" ubiquitous galactic cosmic radiation (GCR) environment combined with--and separate from--the transient challenge of a solar particle event (SPE) was modelled for a simulated 30-day mission period. Simple geometries of relatively thin and uniform shields were chosen to represent the space vehicle and other available shielding, and male or female phantoms were used to represent the body's self-shielding. Absorbed dose in organs and tissues and the effective dose were calculated for males and females. Risk parameters for cancer and other outcomes are presented for selected organs. The results of this intracomparison between ISS Partner Agencies itself provide insights to the level of agreement with which space agencies can perform organ dosimetry and calculate effective dose. This work was performed in collaboration with the advisory and guidance efforts of the International Commission on Radiological Protection (ICRP) Task Group 115 and will be presented in an ICRP Report.
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Radiación Cósmica , Vuelo Espacial , Femenino , Humanos , Masculino , Dosis de Radiación , Radiometría , Nave EspacialRESUMEN
Objective. Time-dependent yields of chemical products resulting from water radiolysis play a great role in evaluating DNA damage response after exposure to ionizing radiation. Particle and Heavy Ion Transport code System (PHITS) is a general-purpose Monte Carlo simulation code for radiation transport, which simulates atomic interactions originating from discrete energy levels of ionizations and electronic excitations as well as molecular excitations as physical stages. However, no chemical code for simulating water radiolysis products exists in the PHITS package.Approach.Here, we developed a chemical simulation code dedicated to the PHITS code, hereafter calledPHITS-Chemcode, which enables the calculation of theGvalues of water radiolysis species (â¢OH, eaq-, H2, H2O2etc) by electron beams.Main results.The estimatedGvalues during 1 µs are in agreement with the experimental ones and other simulations. ThisPHITS-Chemcode also simulates the radiolysis in the presence of OH radical scavengers, such as tris(hydroxymethyl)aminomethane and dimethyl sulfoxide. Thank to this feature, the contributions of direct and indirect effects on DNA damage induction under various scavenging capacities can be analyzed.Significance.This chemical code coupled with PHITS could contribute to elucidating the mechanism of radiation effects by connecting physical, physicochemical, and chemical processes.
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Electrones , Agua , Agua/química , Simulación por Computador , Fenómenos Químicos , Radiación Ionizante , Método de MontecarloRESUMEN
Subfoveal perfluorocarbon liquid (PFL) is a vision-threatening complication that requires removal as safely as possible. We experienced a surgical case of proliferative vitreoretinopathy, in which a subfoveal PFL droplet was removed through the fovea, without puncturing the retina. In this case, although the retina was completely attached after primary vitrectomy and cataract removal, a subfoveal PFL droplet was found. At the second surgery, after peeling the internal limiting membrane, the droplet was passively aspirated by placing a 25-gauge blunt needle on the surface of the retina. This useful technique avoids puncturing the retina and does not require the patient to maintain a specific position postoperatively.
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ABSTRACT: Organ dosimetry data of the atomic bomb survivors and the resulting cancer risk models derived from these data are currently assessed within the DS02 dosimetry system developed through the Joint US-Japan Dosimetry Working Group. In DS02, the anatomical survivor models are limited to three hermaphroditic stylized phantoms-an adult (55 kg), a child (19.8 kg), and an infant (9.7 kg)-that were originally designed for the preceding DS86 dosimetry system. As such, organ doses needed for assessment of in-utero cancer risks to the fetus have continued to rely upon the use of the uterine wall in the adult non-pregnant stylized phantom as the dose surrogate for all fetal organs regardless of gestational age. To address these limitations, the Radiation Effects Research Foundation (RERF) Working Group on Organ Dose (WGOD) has established the J45 (Japan 1945) series of high-resolution voxel phantoms, which were derived from the UF/NCI series of hybrid phantoms and scaled to match mid-1940s Japanese body morphometries. The series includes male and female phantoms-newborn to adult-and four pregnant female phantoms at gestational ages of 8, 15, 25, and 38 wk post-conception. In previous studies, we have reported organ dose differences between those reported by the DS02 system and those computed by the WGOD using 3D Monte Carlo radiation transport simulations of atomic bomb gamma-ray and neutron fields for the J45 phantoms series in their traditional "standing" posture, with some variations in their facing direction relative to the bomb hypocenter. In this present study, we present the J45 pregnant female phantoms in both a "kneeling" and "lying" posture and assess the dosimetric impact of these more anatomically realistic survivor models in comparison to current organ doses given by the DS02 system. For the kneeling phantoms facing the bomb hypocenter, organ doses from bomb source photon spectra were shown to be overestimated by the DS02 system by up to a factor of 1.45 for certain fetal organs and up to a factor of 1.17 for maternal organs. For lying phantoms with their feet in the direction of the hypocenter, fetal organ doses from bomb source photon spectra were underestimated by the DS02 system by factors as low as 0.77, while maternal organ doses were overestimated by up to a factor of 1.38. Organs doses from neutron contributions to the radiation fields exhibited an increasing overestimation by the DS02 stylized phantoms as gestational age increased. These discrepancies are most evident in fetal organs that are more posterior within the mother's womb, such as the fetal brain. Further analysis revealed that comparison of these postures to the original standing posture indicate significant dose differences for both maternal and fetal organ doses depending on the type of irradiation. Results from this study highlight the degree to which the existing DS02 system can differ from organ dosimetry based upon 3D radiation transport simulations using more anatomically realistic models of those survivors exposed during pregnancy.
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Supervivientes a la Bomba Atómica , Traumatismos por Radiación , Recién Nacido , Niño , Adulto , Embarazo , Humanos , Masculino , Femenino , Radiometría/métodos , Feto/efectos de la radiación , PosturaRESUMEN
Objective. Estimation of the probability density of the microdosimetric quantities in macroscopic matter is indispensable for applying the concept of microdosimetry to medical physics and radiological protection. The Particle and Heavy Ion Transport code System (PHITS) enables estimating the microdosimetric probability densities due to its unique hybrid modality between the Monte Carlo and analytical approaches called the microdosimetric function. It can convert the deposition energies calculated by the macroscopic Monte Carlo radiation transport simulation to microdosimetric probability densities in water using an analytical function based on the track-structure simulations.Approach. In this study, we improved this function using the latest track-structure simulation codes implemented in PHITS. The improved function is capable of calculating the probability densities of not only the conventional microdosimetric quantities such as lineal energy but also the number of ionization events occurring in a target site, the so-called ionization cluster size distribution, for arbitrary site diameters from 3 nm to 1µm.Main results. The accuracy of the improved function was well verified by comparing the microdosimetric probability densities measured by tissue-equivalent proportional counters with the corresponding data calculated in this study. Test calculations for clonogenic cell survival using the improved function coupled with the modified microdosimetric kinetic model suggested a slight increase of its relative biological effectiveness compared with our previous estimations. As a new application of the improved function, we calculated the relative biological effectiveness of the single-strand break and double-strand break yields for proton irradiations using the updated PHITS coupled with the simplified DNA damage estimation model, and confirmed its equivalence in accuracy and its superiority in computational time compared to our previously proposed method based on the track-structure simulation.Significance. From these features, we concluded that the improved function could expand the application fields of PHITS by bridging the gap between microdosimetry and macrodosimetry.
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Radiación Ionizante , Radiometría , Método de Montecarlo , Simulación por Computador , Efectividad Biológica Relativa , Probabilidad , Radiometría/métodosRESUMEN
A significant source of information on radiation-induced biological effects following in-utero irradiation stems from studies of atomic bomb survivors who were pregnant at the time of exposure in Hiroshima, and to a lesser extent, from survivors in Nagasaki. Dose estimates to the developing fetus for these survivors have been assigned in prior dosimetry systems of the Radiation Effects Research Foundation as the dose to the uterine wall within the non-pregnant adult stylized phantom, originally designed for the dosimetry system DS86 and then carried forward in DS02. In a prior study, a new J45 (Japanese 1945) series of high-resolution phantoms of the adult pregnant female at 8 weeks, 15 weeks, 25 weeks, and 38-weeks post-conception was presented. Fetal and maternal organ doses were estimated by computationally exposing the pregnant female phantom series to DS02 free-in-air cumulative photon and neutron fluences at three distances from the hypocenter at both Hiroshima and Nagasaki under idealized frontal (AP) and isotropic (ISO) particle incidence. In this present study, this work was extended using realistic angular fluences (480 directions) from the DS02 system for seven radiation source terms, nine different radiation dose components, and five shielding conditions. In addition, to explore the effects of fetal position within the womb, four new phantoms were created and the same irradiation scenarios were performed. General findings are that the current DS02 fetal dose surrogate overestimates values of fetal organ dose seen in the J45 phantoms towards the cranial end of the fetus, especially in the later stages of pregnancy. For example, for in-open exposures at 1000 m in Hiroshima, the ratio of J45 fetal brain dose to DS02 uterine wall dose is 0.90, 0.82, and 0.70 at 15 weeks, 25 weeks, and 38-weeks, respectively, for total gamma exposures, and are 0.64, 0.44, and 0.37 at these same gestational ages for total neutron exposures. For organs in the abdominal and pelvic regions of the fetus, dose gradients across gestational age flatten and later reverse, so that DS02 fetal dosimetry begins to underestimate values of fetal organ dose as seen in the J45 phantoms. For example, for the same exposure scenario, the ratios of J45 fetal kidney dose to DS02 uterine wall dose are about 1.09 from 15 to 38 weeks for total gamma dose, and are 1.30, 1.56, and 1.75 at 15 weeks, 25 weeks, and 38 weeks, respectively, for the total neutron dose. Results using the new fetal positioning phantoms show this trend reversing for a head-up, breach fetal position. This work supports previous findings that the J45 pregnant female phantom series offers significant opportunities for gestational age-dependent assessment of fetal organ dose without the need to invoke the uterine wall as a fetal organ surrogate.
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Guerra Nuclear , Traumatismos por Radiación , Adulto , Femenino , Humanos , Embarazo , Supervivientes a la Bomba Atómica , Radiometría/métodos , Sobrevivientes , Feto , JapónRESUMEN
Objective. The delivery of intensity-modulated radiation fields has improved the conformity of dose to tumour targets during radiotherapy (RT). Previously, it has been shown that intercellular communication between cells positioned in- and outside of the radiation field impacts cellular radiosensitivity under hypoxic and normoxic conditions. However, the mechanism of intercellular communication in hypoxia remains to be fully understood. In this study, the cell-killing effects of intercellular communication in hypoxia were modelled in an effort to better understand the underlying mechanisms of response.Approach. By irradiating a 50% area of the culture dish (half-field exposure), experimental dose-response curves for cell survival and residual DNA double-strand breaks (DSBs) were generated in prostate (DU145) and non-small cell lung cancer (H1299) cells. The oxygen enhancement ratio (OER) was determined from early DSB yields (corresponding to relative direct damage) and used to model the in- and out-of-field radiosensitivity.Main results. The developed integrated microdosimetric-kinetic (IMK) model successfully predicted the experimental dose responses for survival and lethal lesions, and provides a mechanistic interpretation that the probability of hits for releasing cell-killing signals is dependent on oxygen. This experimental and modelling study also suggests that residual DSBs correspond to logarithmic survival fraction (meaning lethal lesions) for in- and out-of-field cells. Our data suggest that the OER value determined using uniform-field exposure can be applied to predict the in- and out-of-field radiosensitivity of cells following exposure to intensity modulated beams.Significance. The developed IMK model facilitates a more precise understanding of intercellular signalling following exposure to intensity-modulated radiation fields.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Masculino , Humanos , Oxígeno , Línea Celular Tumoral , Tolerancia a Radiación , Supervivencia Celular/efectos de la radiación , Hipoxia , Relación Dosis-Respuesta en la Radiación , Daño del ADNRESUMEN
PURPOSE: To compare the accuracy of intraocular lens (IOL) power calculations among IOL formulas after phacovitrectomy. METHODS: We prospectively enrolled 206 eyes of 206 patients who underwent 25-gauge phacovitrectomy, without gas tamponade, for macular pathology. Pre-operative optical biometry used the IOLMaster 700 to calculate the IOL power with the new formulas, i.e. the Barrett Universal II (BU II), Emmetropia Verifying Optical version 2.0, Hill-Radial Basis Function (RBF) version 3.0, Kane, and Ladas Super Formula, and conventional formulas, i.e. Haigis, Hoffer Q, Holladay 1, Holladay 2, and Sanders-Retzlaff-Kraff/T (SRK/T). A single-piece foldable IOL was implanted in all cases. Manifest refractions were measured before and 3 months after surgery. RESULTS: The BU II formula showed the lowest standard deviation and mean and median absolute errors and had the highest percentage of eyes with a refractive prediction error within ± 0.25 D. The absolute error was significantly lower with the four new formulas, except the Hill-RBF, than with the Hoffer Q (all p = ≤ 0.010) and Holladay 1 formulas (all p = < 0.010). The absolute error with the BU II formula was also lower than that with the Holladay 2 (p = 0.012) and SRK/T (p = 0.024) formulas. CONCLUSION: Overall, the new IOL formulas, except the Hill-RBF, were superior to some of the conventional formulas for calculating IOL power in phacovitrectomy.
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Lentes Intraoculares , Facoemulsificación , Errores de Refracción , Humanos , Refracción Ocular , Proyectos Piloto , Biometría , Errores de Refracción/diagnóstico , Estudios Retrospectivos , Óptica y FotónicaRESUMEN
The displacement damage dose (DDD) is a common index used to predict the life of semiconductor devices employed in space-based environments where they will be exposed to radiation. The DDD is commonly estimated from the non-ionizing energy loss based on the Norgett-Robinson-Torrens (NRT) model, although a new definition for a so-called effective DDD considers the molecular dynamic (MD) simulation with the amorphization in semiconductors. The present work developed a new model for calculating the conventional and effective DDD values for silicon carbide (SiC), indium arsenide (InAs), gallium arsenide (GaAs) and gallium nitride (GaN) semiconductors. This model was obtained by extending the displacement per atom tally implemented in the particle and heavy ion transport code system (PHITS). This new approach suggests that the effective DDD is higher than the conventional DDD for arsenic-based compounds due to the amorphization resulting from direct impacts, while this relationship is reversed for SiC because of recombination defects. In the case of SiC and GaN exposed to protons, the effective DDD/conventional DDD ratio decreases with proton energy. In contrast, for InAs and GaAs, this ratio increases to greater than 1 at proton energies up to 100 MeV and plateaus because the defect production efficiency, which is the ratio of the number of stable displacements at the end of collision cascade simulated by MD simulations to the number of defects calculated by NRT model, does not increase at damage energy values above 20 keV. The practical application of this model was demonstrated by calculating the effective DDD values for semiconductors sandwiched between a thin glass cover and an aluminum plate in a low-Earth orbit. The results indicated that the effective DDD could be dramatically reduced by increasing the glass cover thickness to 200 µm, thus confirming the importance of shielding semiconductor devices used in space. This improved PHITS technique is expected to assist in the design of semiconductors by allowing the effective DDD values for various semiconductors having complex geometries to be predicted in cosmic ray environments.
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Protones , SemiconductoresRESUMEN
Proton beam therapy allows irradiating tumor volumes with reduced side effects on normal tissues with respect to conventional x-ray radiotherapy. Biological effects such as cell killing after proton beam irradiations depend on the proton kinetic energy, which is intrinsically related to early DNA damage induction. As such, DNA damage estimation based on Monte Carlo simulations is a research topic of worldwide interest. Such simulation is a mean of investigating the mechanisms of DNA strand break formations. However, past modellings considering chemical processes and DNA structures require long calculation times. Particle and heavy ion transport system (PHITS) is one of the general-purpose Monte Carlo codes that can simulate track structure of protons, meanwhile cannot handle radical dynamics simulation in liquid water. It also includes a simple model enabling the efficient estimation of DNA damage yields only from the spatial distribution of ionizations and excitations without DNA geometry, which was originally developed for electron track-structure simulations. In this study, we investigated the potential application of the model to protons without any modification. The yields of single-strand breaks, double-strand breaks (DSBs) and the complex DSBs were assessed as functions of the proton kinetic energy. The PHITS-based estimation showed that the DSB yields increased as the linear energy transfer (LET) increased, and reproduced the experimental and simulated yields of various DNA damage types induced by protons with LET up to about 30 keVµm-1. These results suggest that the current DNA damage model implemented in PHITS is sufficient for estimating DNA lesion yields induced after protons irradiation except at very low energies (below 1 MeV). This model contributes to evaluating early biological impacts in radiation therapy.
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Electrones , Protones , Daño del ADN , Método de Montecarlo , ADN/químicaRESUMEN
Astatine (211At) is an alpha-emitter with a better treatment efficacy against differentiated thyroid cancer compared with iodine (131I), a conventional beta-emitter. However, its therapeutic comparison has not been fully evaluated. In this study, we compared the therapeutic effect between [211At]NaAt and [131I]NaI. In vitro analysis of a double-stranded DNA break (DSB) and colony formation assay were performed using K1-NIS cells. The therapeutic effect was compared using K1-NIS xenograft mice administered with [211At]NaAt (0.4 MBq (n = 7), 0.8 MBq (n = 9), and 1.2 MBq (n = 4)), and [131I]NaI (1 MBq (n = 4), 3 MBq (n = 4), and 8 MBq (n = 4)). The [211At]NaAt induced higher numbers of DSBs and had a more reduced colony formation than [131I]NaI. In K1-NIS mice, dose-dependent therapeutic effects were observed in both [211At]NaAt and [131I]NaI. In [211At]NaAt, a stronger tumour-growth suppression was observed, while tumour regrowth was not observed until 18, 25, and 46 days after injection of 0.4, 0.8, and 1.2 MBq of [211At]NaAt, respectively. While in [131I]NaI, this was observed within 12 days after injection (1, 3, and 8 MBq). The superior therapeutic effect of [211At]NaAt suggests the promising clinical applicability of targeted alpha therapy using [211At]NaAt in patients with differentiated thyroid cancer refractory to standard [131I]NaI treatment.
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Adenocarcinoma , Astato , Neoplasias de la Tiroides , Adenocarcinoma/tratamiento farmacológico , Animales , Astato/uso terapéutico , Humanos , Radioisótopos de Yodo/uso terapéutico , Ratones , Neoplasias de la Tiroides/tratamiento farmacológico , Neoplasias de la Tiroides/genética , Trasplante HeterólogoRESUMEN
Objective.A retrospective study on secondary cancer risk on carbon ion radiotherapy (CIRT) is ongoing at the Heavy Ion Medical Accelerator in Chiba (HIMAC). The reconstruction of the whole-body patient dose distribution is the key issue in the study because dose distribution only around the planning target volume was evaluated in the treatment planning system.Approach.We therefore developed a new dose reconstruction system based on the Particle and Heavy Ion Transport code System (PHITS) coupled with the treatment plan DICOM data set by extending the functionalities of RadioTherapy package based on PHITS (RT-PHITS). In the system, the geometry of patient-specific beam devices such as the range shifter, range compensator, and collimators as well as the individual patient's body are automatically reconstructed. Various functions useful for retrospective analysis on the CIRT are implemented in the system, such as those for separately deducing dose contributions from different secondary particles and their origins.Main results.The accuracy of the developed system was validated by comparing the dose distribution to the experimental data measured in a water tank and using a treatment plan on an anthropomorphic phantom.Significance.The extended RT-PHITS will be used in epidemiological studies based on clinical data from HIMAC.