Linear Energy Transfer Particles Research Articles

Features of the Effects of Exposure to 90–170 MeV Proton Radiation on the Blood-Forming Organs in Mice under Total Irradiation with Proton Pencil Scanning Beam Depending on the Linear Energy Transfer of Particles

Features of the Effects of Exposure to 90–170 MeV Proton Radiation on the Blood-Forming Organs in Mice under Total Irradiation with Proton Pencil Scanning Beam Depending on the Linear Energy Transfer of Particles

Particle tracking, recognition and LET evaluation of out-of-field proton therapy delivered to a phantom with implants

Objective. This study aims to assess the composition of scattered particles generated in proton therapy for tumors situated proximal to some titanium (Ti) dental implants. The investigation involves decomposing the mixed field and recording Linear Energy Transfer (LET) spectra to quantify the influence of metallic dental inserts located behind the tumor. Approach. A therapeutic conformal proton beam was used to deliver the treatment plan to an anthropomorphic head phantom with two types of implants inserted in the target volume (made of Ti and plastic, respectively). The scattered radiation resulted during the irradiation was detected by a hybrid semiconductor pixel detector MiniPIX Timepix3 that was placed distal to the Spread-out Bragg peak. Visualization and field decomposition of stray radiation were generated using algorithms trained in particle recognition based on artificial intelligence neural networks (AI NN). Spectral sensitive aspects of the scattered radiation were collected using two angular positions of the detector relative to the beam direction: 0° and 60°. Results. Using AI NN, 3 classes of particles were identified: protons, electrons & photons, and ions & fast neutrons. Placing a Ti implant in the beam’s path resulted in predominantly electrons and photons, contributing 52.2% of the total number of detected particles, whereas for plastic implants, the contribution was 65.4%. Scattered protons comprised 45.5% and 31.9% with and without metal inserts, respectively. The LET spectra were derived for each group of particles identified, with values ranging from 0.01 to 7.5 keV μm−1 for Ti implants/plastic implants. The low-LET component was primarily composed of electrons and photons, while the high-LET component corresponded to protons and ions. Significance. This method, complemented by directional maps, holds the potential for evaluating and validating treatment plans involving stray radiation near organs at risk, offering precise discrimination of the mixed field, and enhancing in this way the LET calculation.

Radiation-induced DNA damage by proton, helium and carbon ions in human fibroblast cell: Geant4-DNA and MCDS-based study

Background. Radiation-induced DNA damages such as Single Strand Break (SSB), Double Strand Break (DSB) and Complex DSB (cDSB) are critical aspects of radiobiology with implications in radiotherapy and radiation protection applications. Materials and Methods. This study presents a thorough investigation into the effects of protons (0.1–100 MeV/u), helium ions (0.13–100 MeV/u) and carbon ions (0.5–480 MeV/u) on DNA of human fibroblast cells using Geant4-DNA track structure code coupled with DBSCAN algorithm and Monte Carlo Damage Simulations (MCDS) code. Geant4-DNA-based simulations consider 1 μm × 1 μm × 0.5 μm water box as the target to calculate energy deposition on event-by-event basis and the three-dimensional coordinates of the interaction location, and then DBSCAN algorithm is used to calculate yields of SSB, DSB and cDSB in human fibroblast cell. The study investigated the influence of Linear Energy Transfer (LET) of protons, helium ions and carbon ions on the yields of DNA damages. Influence of cellular oxygenation on DNA damage patterns is investigated using MCDS code. Results. The study shows that DSB and SSB yields are influenced by the LET of the particles, with distinct trends observed for different particles. The cellular oxygenation is a key factor, with anoxic cells exhibiting reduced SSB and DSB yields, underscoring the intricate relationship between cellular oxygen levels and DNA damage. The study introduced DSB/SSB ratio as an informative metric for evaluating the severity of radiation-induced DNA damage, particularly in higher LET regions. Conclusions. The study highlights the importance of considering particle type, LET, and cellular oxygenation in assessing the biological effects of ionizing radiation.

10255-BOT-5 EXOSOMAL MIRNAS RELEASED FROM GLIOBLASTOMA CELLS AFTER BNCT TARGET CELL PROLIFERATION AND SURVIVAL SIGNALS

Abstract Boron neutron capture therapy (BNCT) is a tumor -selective particle radiation therapy. In BNCT, p-boronophenyl alanine, which is actively taken up by tumor cells through LAT1 transporter, a member of the system L family of heterodimeric, sodium-independent, amino acid transporters, is administrated to patients, and thermal or epithermal neutron is irradiated to tumor tissue of the patients. Nuclear capture and fission reactions between boron-10 and thermal neutron occurred only in tumor cells produce high- linear energy transfer (LET) alpha particles and recoiling lithium-7 (7Li). These high LET particles have very short pathlength (5-9 μmeter), and kill boron-10 containing tumor cells sparing adjacent normal tissue cells. BNCT was applied to malignant glioma, the most devastating tumor and has prolonged the survival of malignant glioma patients. In this study, we comprehensively investigated the micro RNAs (miRNAs) in exosomes derived from BNCT-treated glioblastoma U87 MG cells using microarray. Comparing with non-treated cells, more than 300 up-regulated miRNAs or 100 down-regulated miRNAs were detected in BNCT-treated cells. From the results of the prediction analysis of the target genes which interact with the miRNAs, the pathway analysis was performed. We found significantly associated pathways, such as Focal adhesion-PI3K-Akt-mTOR, Ras, MAPK, etc. miRNAs in exosomes released from BNCT-treated glioblastoma cells may suppress such essential pathways for cell proliferation and survival.

Alpha‐emitters and targeted alpha therapy in cancer treatment

AbstractAlpha emitters are radionuclides with good pharmacological characteristics for the treatment of cancer because they decay by emitting high linear energy transfer particles. Recent advancements in isotope production and purification and the generation of novel techniques for optimum targeting have led to the development of targeted alpha therapy (TAT). The great cytotoxic potential of α‐particle emissions combined with monoclonal antibodies, peptides, small compounds, or nanoparticles has led to investigations of TAT in the pre‐clinical context and more recently, in oncology clinical trials. Numerous studies have shown that TAT is effective both in vitro and in vivo. The first α‐emitter to obtain FDA approval for the treatment of prostate cancer with metastatic bone lesions was radium‐223 dichloride. Many clinical trials are being conducted to evaluate the efficiency and safety of several radionuclides in cancer treatment, including radium‐223, astatine‐211, actinium‐225, bismuth‐213, lead‐212, and thorium‐227. This review provides an overview of the therapeutic use of these radionuclides and a summary of the studies that lay the groundwork for future clinical advancement.

Oxide Electric Field-Induced Degradation of SiC MOSFET for Heavy-Ion Irradiation

This work presents an experimental study of heavy-ion irradiation with different particle linear energy transfer (LET), gate biases, and drain biases. The results reveal that when the irradiation biases are low, the SiC MOSFET does not experience single event effect (SEE) and the electrical properties remain unchanged (the devices are in the safe operating area (SOA)). However, the oxide breakdown voltage of the device is significantly decreased due to the latent damage generated by the irradiation. The experimental results, along with TCAD simulations, suggest that the latent damage induced by the irradiation in the gate oxide is closely related to the peak electric field in the gate oxide at the time of particle incidence. This peak electric field is determined by the potential difference between the two sides of the gate oxide, which is affected by the particle LET, gate biases, and drain biases together. The high potential is determined by the combined effect of the LET and the drain-source voltage. The impact ionization of the particle by the applied electric field causes the accumulation of holes in the JFET oxide, which leads to a decrease in the doping of the N− epitaxial layer and eventually causes a rise in the high potential near the JFET oxide. The low potential is determined by the gate bias, and the negative bias applied to the gate can further increase the potential difference between the two sides of the oxide, causing an increase in the peak electric field in the gate oxide and aggravating the gate oxide damage.

Relative efficiency of radiophotoluminescent glass detectors in low energy ion beams

In heavy charged particle dosimetry, the luminescence efficiency strongly depends on linear energy transfer (LET) and characterization of the detectors' efficiency as a function of the particle LET is very important. Available literature data for the efficiency of radiophotoluminescent (RPL) glass detectors are scarce and especially for low energy range no data was found. In this study, detectors made of the most widely known RPL material (silver activated phosphate glass) were exposed to various low energy ion beams (1H, 7Li, and 12C). For every ion beam, the linear dose (fluence) response of the RPL glass detectors was confirmed for the investigated dose (fluence) range and the RPL efficiency relative to 60Co gamma rays was evaluated. The relative efficiency decreased as LET increased but not as a unique function of LET, where the relative efficiency (expressed for doses in RPL glass) decreased from 0.85 ± 0.06 for the 5 MeV 1H ion beam (LETw = 8.1 keV/μm) to 0.017 ± 0.001 for the 15 MeV 12C ion beam (LETw = 673.8 keV/μm). More experimental data are still needed but results obtained in this study may motivate the application and testing of microdosimetric models for RPL glass detectors.

Clonogenic assay to measure bystander cytotoxicity of targeted alpha-particle therapy.

Radiation therapy induces targeted effects in the cells that are irradiated and also non-targeted effects (i.e. bystander effects) in non-irradiated cells that are close to or at short distance (<∼1mm) from irradiated cells. Bystander effects are mediated by intercellular communications and may result in cytotoxic and genotoxic modifications. Their occurrence and relative contribution to the irradiation outcome are influenced by several parameters among which the particle linear energy transfer seems to be prominent. Bystander effects were first observed after external radiation therapy, but have been described also following targeted radionuclide therapy. Therefore, we propose a method to investigate their occurrence in experimental conditions where cells are exposed to radiopharmaceuticals. In this approach, clonogenic cell death is the biological endpoint of the bystander effects caused by irradiation with alpha particles (a potent inducer of the bystander response).

A phenomenological model of proton FLASH oxygen depletion effects depending on tissue vasculature and oxygen supply.

Radiation-induced oxygen depletion in tissue is assumed as a contributor to the FLASH sparing effects. In this study, we simulated the heterogeneous oxygen depletion in the tissue surrounding the vessels and calculated the proton FLASH effective-dose-modifying factor (FEDMF), which could be used for biology-based treatment planning. The dose and dose-weighted linear energy transfer (LET) of a small animal proton irradiator was simulated with Monte Carlo simulation. We deployed a parabolic partial differential equation to account for the generalized radiation oxygen depletion, tissue oxygen diffusion, and metabolic processes to investigate oxygen distribution in 1D, 2D, and 3D solution space. Dose and dose rates, particle LET, vasculature spacing, and blood oxygen supplies were considered. Using a similar framework for the hypoxic reduction factor (HRF) developed previously, the FEDMF was derived as the ratio of the cumulative normoxic-equivalent dose (CNED) between CONV and UHDR deliveries. Dynamic equilibrium between oxygen diffusion and tissue metabolism can result in tissue hypoxia. The hypoxic region displayed enhanced radio-resistance and resulted in lower CNED under UHDR deliveries. In 1D solution, comparing 15 Gy proton dose delivered at CONV 0.5 and UHDR 125 Gy/s, 61.5% of the tissue exhibited ≥20% FEDMF at 175 μm vasculature spacing and 18.9 μM boundary condition. This percentage reduced to 34.5% and 0% for 8 and 2 Gy deliveries, respectively. Similar trends were observed in the 3D solution space. The FLASH versus CONV differential effect remained at larger vasculature spacings. A higher FLASH dose rate showed an increased region with ≥20% FEDMF. A higher LET near the proton Bragg peak region did not appear to alter the FLASH effect. We developed 1D, 2D, and 3D oxygen depletion simulation process to obtain the dynamic HRF and derive the proton FEDMF related to the dose delivery parameters and the local tissue vasculature information. The phenomenological model can be used to simulate or predict FLASH effects based on tissue vasculature and oxygen concentration data obtained from other experiments.

A Review of Boron Neutron Capture Therapy: Its History and Current Challenges.

Mechanism of ActionExternal beam, whether with photons or particles, remains as the most common type of radiation therapy. The main drawback is that radiation deposits dose in healthy tissue before reaching its target. Boron neutron capture therapy (BNCT) is based on the nuclear capture and fission reactions that occur when 10B is irradiated with low-energy (0.0025 eV) thermal neutrons. The resulting 10B(n,α)7Li capture reaction produces high linear energy transfer (LET) α particles, helium nuclei (4He), and recoiling lithium-7 (7Li) atoms. The short range (5-9 μm) of the α particles limits the destructive effects within the boron-containing cells. In theory, BNCT can selectively destroy malignant cells while sparing adjacent normal tissue at the cellular levels by delivering a single fraction of radiation with high LET particles.HistoryBNCT has been around for many decades. Early studies were promising for patients with malignant brain tumors, recurrent tumors of the head and neck, and cutaneous melanomas; however, there were certain limitations to its widespread adoption and use.Current Limitations and ProspectsRecently, BNCT re-emerged owing to several developments: (1) small footprint accelerator-based neutron sources; (2) high specificity third-generation boron carriers based on monoclonal antibodies, nanoparticles, among others; and (3) treatment planning software and patient positioning devices that optimize treatment delivery and consistency.

Demonstration of an optically stimulated luminescence (OSL) material with reduced quenching for proton therapy dosimetry: MgB4O7:Ce,Li

The objective of this work is to demonstrate that MgB4O7:Ce,Li, a new optically stimulated luminescence (OSL) dosimetric material, shows improved response for proton therapy dosimetry, with less reduction in luminescence detector efficiency with the particle linear energy transfer (LET). MgB4O7:Ce,Li was synthesized and its luminescence efficiency as a function of LET was characterized for dose-averaged LET values from 0.73 keV/μm up to 74.9 keV/μm using proton, 4He, and 12C ion beams. Commercial Al2O3:C OSLDs were also used for comparison. Monte Carlo simulations were used to predict the material's response in pristine and spread-out Bragg peaks (SOBP), suggesting the MgB4O7:Ce,Li would offer minimum quenching in proton beams of energies relevant to radiotherapy. This prediction was confirmed by irradiations of MgB4O7:Ce,Li and Al2O3:C along SOBPs from proton beams. The results demonstrate that new OSL materials optimized for proton dosimetry can be developed using their dose response to low-LET radiation as a guide during material development.

Theoretical and experimental estimation of the relative optically stimulated luminescence efficiency of an optical-fiber-based BaFBr:Eu detector for swift ions

ABSTRACT The reliability of dose assessment with radiation detectors is an important feature in various fields, such as radiotherapy, radiation protection, and high-energy physics. However, many detectors irradiated by high linear energy transfer (LET) radiations exhibit decreased efficiency called the quenching effect. This quenching effect depends not only on the particle LET but also strongly on the ion species and its microscopic pattern of energy deposition. Recently, a computational method for estimating the relative efficiency of luminescence detectors has been proposed following the analysis of microdosimetric specific energy distributions simulated using the particle and heavy ion transport code system (PHITS). This study applied the model to estimate the relative optically stimulated luminescence (OSL) efficiency of BaFBr:Eu detectors. Additionally, we measured the luminescence intensity of BaFBr:Eu detectors exposed to 4He, 12C, and 20Ne ions to verify the calculated data. The model reproduced the experimental data in the cases of adopting a microdosimetric target diameter of approximately 30–50 nm. The calculated relative efficiency exhibits ion-species dependence in addition to LET. This result shows that the microdosimetric calculation from specific energy is a successful method for accurately understanding the results of OSL measurements with BaFBr:Eu detectors irradiated by various particles.

Carbon ion radiation and clustered DNA double-strand breaks.

A carbon ion categorized as a heavy ion particle has been used for cancer radiotherapy. High linear energy transfer (LET) carbon ion irradiation deposits energy at a high density along a particle track, generating multiple types of DNA damage. Complex DNA lesions, comprising DNA double-strand breaks (DSBs), single-strand breaks, and base damage within 1-2 helical turns (<3-4nm), are thought to be difficult to repair and critically influence cell viability. In addition to the effect of lesion complexity, the most recent studies have demonstrated another characteristic of high LET particle radiation-induced DNA damage, clustered DSBs. Clustered DSBs are defined as the formation of multiple DSBs in close proximity where the scale of clustering is approximately 1-2μm3, i.e., the scale of the event is estimated to be > ∼1Mbp. This chapter reviews the hallmarks of clustered DSBs and how such DNA damage influences genome instability and cell viability in the context of high LET carbon ion radiotherapy.

A Comparative Study of Single-Event-Burnout for 4H-SiC UMOSFET

SiC UMOSFET is a kind of significant power device in the supply of aerospace. But it is sensitive to space radiation. In this paper, the discrepancy of SEB behavior and research of 4H-SiC UMOSFET with the different values of particle linear energy transfer (LET) are proposed and investigated by the 2D numerical simulations. And the improved MOSFET with multi-Buff was compared with the conventional UMOSFET. At last, simulation results demonstrated that under high-intensity radiation environment (high LET value heavy ion incidence), the proposed UMOSFET could increase the single-event burnout (SEB) hardness, and using the lattice temperature of device as the SEB behavior characterization of the SiC UMOSFET after heavy ion incidence is more reasonable and accurate than only using high steady-state drain current.

Role of Mitochondria in Radiation Responses: Epigenetic, Metabolic, and Signaling Impacts.

Until recently, radiation effects have been considered to be mainly due to nuclear DNA damage and their management by repair mechanisms. However, molecular biology studies reveal that the outcomes of exposures to ionizing radiation (IR) highly depend on activation and regulation through other molecular components of organelles that determine cell survival and proliferation capacities. As typical epigenetic-regulated organelles and central power stations of cells, mitochondria play an important pivotal role in those responses. They direct cellular metabolism, energy supply and homeostasis as well as radiation-induced signaling, cell death, and immunological responses. This review is focused on how energy, dose and quality of IR affect mitochondria-dependent epigenetic and functional control at the cellular and tissue level. Low-dose radiation effects on mitochondria appear to be associated with epigenetic and non-targeted effects involved in genomic instability and adaptive responses, whereas high-dose radiation effects (>1 Gy) concern therapeutic effects of radiation and long-term outcomes involving mitochondria-mediated innate and adaptive immune responses. Both effects depend on radiation quality. For example, the increased efficacy of high linear energy transfer particle radiotherapy, e.g., C-ion radiotherapy, relies on the reduction of anastasis, enhanced mitochondria-mediated apoptosis and immunogenic (antitumor) responses.

Measurement of therapeutic 12C beam in a water phantom using CR-39

The motivation for this study was to explore a new method to test the particle spatial distribution for a therapeutic carbon beam. CR-39 plastic nuclear track detectors were irradiated to a 276.5 MeV u−1 mono-energy carbon beam at the heavy ion facility in the Shanghai Proton and Heavy Ion Center. The spatial distribution of the primary carbon beam and secondary fragments in a water phantom were systematically analyzed both in the transverse direction (perpendicular to the projection direction of the primary beam) and at different depths in the longitudinal direction (along the projection direction of the primary beam) with measured tracks on the CR-39 detectors. Meanwhile, the theoretically spatial distribution and linear energy transfer (LET) spectra of the primary beam and secondary fragments were calculated using the Monte Carlo (MC) toolkit Geant4. The results showed that the CR-39 detectors are capable of providing high lateral resolution of carbon ion at different depths. In the range of the primary carbon beam, the beam width simulated with MC is in good agreement with that of experimental measurement. The track size registered in the CR-39 has a good correlation with the particle LET. These findings indicate that the CR-39 can be used for measuring both the particle flux and its spatial distribution of carbon ions.

Molecular Mechanisms of Specific Cellular DNA Damage Response and Repair Induced by the Mixed Radiation Field During Boron Neutron Capture Therapy.

The impact of a mixed neutron-gamma beam on the activation of DNA damage response (DDR) proteins and non-coding RNAs (ncRNAs) is poorly understood. Ionizing radiation is characterized by its biological effectiveness and is related to linear energy transfer (LET). Neutron-gamma mixed beam used in boron neutron capture therapy (BNCT) can induce another type of DNA damage such as clustered DNA or multiple damaged sites, as indicated for high LET particles, such as alpha particles, carbon ions, and protons. We speculate that after exposure to a mixed radiation field, the repair capacity might reduce, leading to unrepaired complex DNA damage for a long period and may promote genome instability and cell death. This review will focus on the poorly studied impact of neutron-gamma mixed beams with an emphasis on DNA damage and molecular mechanisms of repair. In case of BNCT, it is not clear which repair pathway is involved, and recent experimental work will be presented. Further understanding of BNCT-induced DDR mechanisms may lead to improved therapeutic efficiency against different tumors.

Monitoring of Particle Count Rate and LET Variations With Pulse Stretching Inverters

This study investigates the use of pulse stretching (skew-sized) inverters for monitoring the variation of count rate and linear energy transfer (LET) of energetic particles. The basic particle detector is a cascade of two pulse stretching inverters, and the required sensing area is obtained by connecting up to 12 two-inverter cells in parallel and employing the required number of parallel arrays. The incident particles are detected as single-event transients (SETs), whereby the SET count rate denotes the particle count rate, while the SET pulsewidth distribution depicts the LET variations. The advantage of the proposed solution is the possibility to sense the LET variations using fully digital processing logic. SPICE simulations conducted on IHP's 130-nm CMOS technology have shown that the SET pulsewidth varies by approximately 550 ps over the LET range from 1 to 100 MeV ·cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> ·mg <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-1</sup> . The proposed detector is intended for triggering the fault-tolerant mechanisms within a self-adaptive multiprocessing system employed in space. It can be implemented as a standalone detector or integrated in the same chip with the target system.

Development of Next Generation Biomedical Sensor for Single Cell Four Dimensional Tracing of Cellular Response to Ion Beam Irradiation

Clonogenic survival of few colonies out of a population of cells that have received a defined amount of energy (J) per mass (kg) represented by the dose unit Gray (Gy) constitutes the gold standard method for quantifying radiobiological effects. We aimed to engineer the next generation biophysical hybrid detector technology using ion beam irradiation with clinical high linear energy transfer (LET) carbon ions combined with 4D single cell fate imaging. Development of a novel biomedical sensor (Cell-Fit-HD4D) and the first successful deconvolution of individual cell fate in response to microscopic ion beam deposition visualized by optical microscopy is reported. Cell-Fit-HD4D enabled single-cell dosimetry in clinically relevant complex radiation fields. A spectrum of experimentally derived physical parameter such as the quantity and the sum of LETs (ΣLET) of primary carbon ion particles traversing cell nuclei were correlated with biological endpoints i.e., DNA-Damage repair kinetic, chronic cell cycle arrest (senescence) and clonogenic survival. Decrypting the physical dose and molecular effects at single cell resolution via Cell-Fit-HD 4D has the potential to revolutionize our comprehension of radiobiological dose concept.

Computation of linear energy transfer of space radiation in biological tissue analog

Charged particle linear energy transfer (LET) distributions of the inner radiation field within an interplanetary spacecraft caused by Galactic Cosmic Radiation (GCR) are a good criterion of adequacy for accelerator-based GCR simulation. This paper presents the results of calculating the LET spectra inside the habitable module of the spacecraft (15 ​g/cm2 of Al shell) at the minimum and maximum of solar activity and comparing the calculations with the data obtained by the RAD dosimeter on the flight path to Mars in 2012. It is shown that the shape of the LET spectra weakly depends on the variation of solar activity over a wide range.