Dose Enhancement Factor Research Articles

Catalytically Active Ti-Based Nanomaterials for Hydroxyl Radical Mediated Clinical X-Ray Enhancement.

Nanoparticle radioenhancement offers a promising strategy for augmenting radiotherapy by locally increasing radiation damage to tumor tissue. While past research has predominantly focused on nanomaterials with high atomic numbers, such as Au and HfO2, recent work has revealed that their radioenhancement efficacy decreases considerably when using clinically relevant megavoltage X-rays as opposed to the orthovoltage X-rays typically employed in research settings. Here, radiocatalytically active Ti-based nanomaterials for clinical X-ray therapy settings are designed. A range of candidate materials, including TiO2 (optionally decorated with Ag or Pt nanoseeds), Ti-containing metal-organic frameworks (MOFs), and 2D Ti-based carbides known as Ti3C2Tx MXenes, is investigated. It is demonstrated that these titanium-based candidates remain consistently performant across a wide energy spectrum, from orthovoltage to megavoltage. This sustained performance is attributed to the catalytic generation of reactive oxygen species, moving beyond the simple physical dose enhancements associated with photoelectric effects. Beyond titania, emergent materials like titanium-based MOFs and MXenes exhibit encouraging results, achieving dose-enhancement factors of up to three in human soft tissue sarcoma cells. Notably, these enhancements are absent in healthy human fibroblast cells under similar conditions of particle uptake, underscoring the selective impact of titanium-based materials in augmenting radiotherapy across the clinically relevant spectral range.

Study of a gel dosimeter based on Ag nanoparticles for applications in radiation therapy with synchrotron X-rays at ultrahigh dose rate compared to 60Co γ-rays

A silver nitrate (AgNO3) gel was developed and evaluated as a dosimeter for synchrotron X-ray-based studies in microbeam radiation therapy (MRT) and FLASH radiation therapy. The gel was irradiated at the European Synchrotron Radiation Facility (ID17 Biomedical beamline) with a continuous X-ray spectrum in the 50-600 keV range and a dose rate of 11.6kGy/s. The spectrophotometric response after irradiation at this beamline was compared with the response at a conventional 60Co γ-ray source providing a dose rate of 0.27 Gy/s. Ag+ ions in the gel dosimeter undergo reduction to Ago nanoparticles, as detected at 450 nm, which is a surface plasmon resonance band. The intensity of this band increased linearly with increasing absorbed dose up to 100 Gy, and improved with the addition of glycerol. The gel dosimeter exhibited the lowest detectable dose (LDD) of 75.9% lower and a dose deposition of 76% higher for ID17 beamline irradiation than for 60Co irradiation. The theoretical relative response HQ,Qo for the gel irradiated at the synchrotron was 1.70, which is in close agreement with the experimental relative response FQ,Qo = 1.76. These results confirm the dose enhancement in the gel irradiated with orthovoltage X-rays. The good properties of the silver nitrate gel, together with its increased sensitivity to orthovoltage X-ray irradiation and modest overall uncertainty of 5.8% (2σ), confirm that the gel is a valid dosimeter for measurements at ultrahigh dose rates for synchrotron radiotherapy. The dosimeter is also a promising candidate for dose enhancement factor measurements in nanoparticle-based radiotherapy techniques.

In silico estimation of polyethylene glycol coating effect on metallic NPs radio-sensitization in kilovoltage energy beams

PurposeNanoparticles (NPs) as radiosensitizers present a promising strategy for enhancing radiotherapy effectiveness, but their potential is significantly influenced by the properties of their surface coating, which can impact treatment outcomes. Most Monte Carlo studies have focused on metallic NPs without considering the impact of coating layers on radiosensitization. In this study, we aim to assess both the physical and radiobiological effects of nanoparticle coatings in nanoparticle-based radiation therapy.Materials and methodsIn this simulation study, we used Geant4 Monte Carlo (MC) toolkit (v10.07.p02) and simulated the bismuth, gold, iridium and gadolinium NPs coated with polyethylene glycol (PEG-400: Density: 1.13 g/cm³, Molar mass: 380–420 g/mol) as radiosensitizer for photon beams of 30, 60 and 100 keV. Secondary electron number and reactive oxygen species enhancement factor were estimated. Also, dose enhancement factor (DEF) was determined in spherical shells with logarithmic scale thickness from the nanoparticle surface to 4 mm.ResultsSecondary electron emission was highest at 30 keV for gold, bismuth, and iridium NPs, while gadolinium NPs peaked at 60 keV. Coating reduced electron emissions across all energies, with thicker coatings leading to a more significant decrease. DEF values declined with increasing radial distance from the NP surface and were lower with thicker coatings. For gadolinium NPs, DEF behavior differed due to K-edge energy effects. Reactive species generation varied, showing maximum production at 30 keV for gold, bismuth, and iridium NPs, while gadolinium NPs showed peak activity at 60 keV. PEG coatings enhanced reactive species formation at 100 keV.ConclusionThe findings indicate that the coating layer thickness and material not only influence the emission of secondary particles and DEF but also affect the generation of reactive species from water radiolysis. Specifically, thicker coatings reduce secondary particle emission and DEF, while PEG coatings demonstrate a dual behavior, offering both protective and enhancing effects depending on photon energy. These insights underscore the importance of optimizing NP design and coating in future studies to maximize therapeutic efficacy in nanoparticle-based radiation therapy.

Nanoscale dosimetry for a radioisotope-labeled metal nanoparticle using MCNP6.2 and Geant4.

Metal nanoparticles (MNPs) labeled with radioisotopes (RIs) are utilized as radio-enhancers due to their ability to amplify the radiation dose in their immediate vicinity. A thorough understanding of nanoscale dosimetry around MNPs enables their effective application in radiotherapy. However, nanoscale dosimetry around MNPs still requires further investigation. This study aims to provide insight into the radio-enhancement effects of MNPs by elucidating nanoscale dosimetry surrounding MNPs labeled with Auger-emitting RIs. We particularly focus on distinguishing the respective dose contributions of photons and electrons emitted by Auger-emitting RIs in the context of dose enhancement. A 50nm diameter NP of silver (Ag) core and gold (Au) shell (Ag@Au NP) was assumed to emit mono-energetic electrons and photons (3, 5, 10, 20, and 30keV), or the energy spectrum corresponding to one of three Auger-emitting RIs (103Pd, 125I, and 131Cs) from the Ag core. Nanoscale radial dose distributions around a single radioactive Ag@Au NP were evaluated in spherical shells of water. Monte Carlo simulations were conducted using single-event and track structure transport methods implemented in MCNP6.2 and Geant4-DNA-Au physics, respectively. To evaluate the extent of radio-enhancement by the Ag@Au NP, two scenarios were considered: Ag@Au NPs (Au shell included) and Ag@water NPs (Au shell replaced by water). The radial doses of 10, 20, and 30keV electrons estimated by both codes were comparable. However, the radial doses of 3 and 5keV electrons by MCNP6.2 were much larger near the NP surface than those by Geant4. There was a dose enhancement of a few % to tens % by the Au shell in the region of the NP surface to 10µm, depending on the electron energy. The radial doses of photons with the Au shell were higher up to their secondary electron ranges than those without the Au shell. The maximum dose enhancement factor of photons occurred at 20keV and was 63.4 by MCNP6.2 and 50.5 by Geant4. The overall radial doses of electrons were 1-2 orders of magnitude larger than those of photons. As a result, in cases of RIs emitting both electrons and photons, the radial doses up to electron ranges were dominantly governed by electrons. The dose enhancement estimated by both codes for the RIs ranged from a few % except in the immediate vicinity of the NP surface. Given the dominant contribution of electrons to radial doses of MNP labeled with Auger-emitting RIs, physical dose enhancement expected by interactions with photons was hindered. Since there are no available RIs emitting exclusively photons, achieving enhanced physical doses within a cell through a combination of MNPs and RIs appears currently unattainable. The radial doses of photons near the NP surface exhibited considerable discrepancies between the codes, primarily attributed to low-energy electrons. The difference may arise from higher cross-sections of Au inelastic scattering in Geant4-DNA-Au compared to MCNP6.2.

Microdosimetric Simulation of Gold-Nanoparticle-Enhanced Radiotherapy.

Conventional X-ray therapy (XRT) is commonly applied to suppress cancerous tumors; however, it often inflicts collateral damage to nearby healthy tissue. In order to provide a better conformity of the dose distribution in the irradiated tumor, proton therapy (PT) is increasingly being used to treat solid tumors. Furthermore, radiosensitization with gold nanoparticles (GNPs) has been extensively studied to increase the therapeutic ratio. The mechanism of radiosensitization is assumed to be connected to an enhancement of the absorbed dose due to huge photoelectric cross-sections with gold. Nevertheless, numerous theoretical studies, mostly based on Monte Carlo (MC) simulations, did not provide a consistent and thorough picture of dose enhancement and, therefore, the radiosensitization effect. Radiosensitization by nanoparticles in PT is even less studied than in XRT. Therefore, we investigate the physics picture of GNP-enhanced RT using an MC simulation with Geant4 equipped with the most recent physics models, taking into account a wide range of physics processes relevant for realistic PT and XRT. Namely, we measured dose enhancement factors in the vicinity of GNP, with diameters ranging from 10 nm to 80 nm. The dose enhancement in the vicinity of GNP reaches high values for XRT, while it is very modest for PT. The macroscopic dose enhancement factors for realistic therapeutic GNP concentrations are rather low for all RT scenarios; therefore, other physico-chemical and biological mechanisms should be additionally invoked for an explanation of the radiosensitization effect observed in many experiments.

An Analysis of the Radiosensitiser Applications in the Biomedical Field.

Various types of radiosensitisers have been introduced from the past until the present day for applications in the biomedical field. However, there is a lack of understanding and comparison between the various parameters introduced in addition to a lack of consensus among researchers on the optimal radiosensitiser for applications in the biomedical field. This review aimed to investigate the usage of radiosensitisers in the biomedical field, determine their important parameters, and suggest radiosensitisers with potential among the analysed radiosensitisers. This review has discussed several parameters for radiosensitisers, including median lethal dose, cell survival, tumour size, cell viability, Dose Enhancement Factor (DEF), Reactive Oxygen Species (ROS) concentration, radiosensitiser production complexity, radiosensitiser administration technique, and radiosensitiser toxicity. General trends regarding the development of radiosensitisers, including the types, effectiveness, and their production complexity, have also been discussed within this review article.

Radiosensitization with metallic nanoparticles under MeV proton beams: local dose enhancement.

In addition to specific dosimetric properties of protons, their higher biological effectiveness makes them superior to X-rays and gamma radiation, in radiation therapy. In recent years, enrichment of tumours with metallic nanoparticles as radiosensitizer agents has generated high interest, with several studies attempting to confirm the efficacy of nanoparticles in proton therapy. In the present study Geant4 Monte Carlo (MC) code was used to quantify the increased nanoscopic dose deposition of 50nm metallic nanoparticles including gold, bismuth, iridium, and gadolinium in water upon exposure to 5, 25, and 50MeV protons. Dose enhancement factors, radial dose distributions in nano-scale, as well as secondary electron and photon energy spectra were calculated for the studied nanoparticles and proton beams. The obtained results demonstrated that in the presence of metallic nanoparticles an increase in proton energy leads to a decrease in secondary electron and photon production yield. Additionally, an increase in the radial dose enhancement factor from 1.4 to 16 was calculated for the studied nanoparticles when the proton energy was increased from 5 to 50MeV. It is concluded that the dosimetric advantages of proton beams could be improved significantly in the presence of metallic nanoparticles.

Gold nanoparticle effect on dose and DNA damage enhancement in the vicinity of gold nanoparticles

This study uses Monte Carlo simulations to examine the dose enhancement effect of gold nanoparticles (AuNPs) in radiation therapy and its effects on DNA damage. Using the GATE- 9.0 and Geant4-DNA packages, Monte Carlo simulations were used to simulate a mathematical phantom and determine the energy deposition in the vicinity of AuNP. The simulations were conducted for various photon beam energies (50, 100, 250, and 6000 keV) with and without the presence of different-size AuNPs (10, 30, 50 and 100 nm). The dose enhancement factor (DER) was evaluated using Geant4-DNA to examine the effects AuNP sizes and photon beam energies on DNA damage. A multi-scale Monte Carlo simulation was conducted to evaluate enhanced DNA damage owing to nanoparticles in the proximity of cancer cells. The Monte Carlo simulations indicated that AuNPs boost the dose delivery, resulting in enhanced energy deposition and subsequent DNA damage. The DER analysis revealed a significant increase in the dose deposition within DNA, leading to single or double-strand breaks. Geant4-DNA simulations revealed information on the dosage enhancement factor for various AuNP sizes and photon beam intensities, enabling a deeper comprehension of the underlying mechanics. The outcomes of this study emphasize the potential of AuNPs as effective radiosensitizers in radiation therapy and contribute to the growing body of research on the use of nanotechnology in enhancing cancer treatment outcomes. Further investigations and experimental validations are necessary to optimize the usage of AuNPs for improved radiation therapy.

A simulation study on the effect of penetration of gold nanoparticles in the cytoplasm of healthy eye organs on dose enhancement of brachytherapy

Purpose Special properties and recent advances in the synthesis and biomolecular functionalization of gold nanoparticles (GNPs) have led to the evolution of their use in biomedical applications such as photon radiotherapy. Simulation-based studies on the effect of various parameters that govern the dose enhancement due to utilizing GNPs have facilitated the progress of knowledge in this field. Due to their flexibility and easier accessibility compared with experimental works, simulations have the potential to be considered for pre-clinical tests and, therefore, should be close to the realistic conditions as much as possible. Materials and methods To this aim, the present work investigates the effect of the presence of GNPs that are accumulated in the cytoplasm of the constituent cells in healthy tissues of a human eye phantom, inspired by the published experimental results which report that non-target tissues also receive the drugs containing GNPs. The GNPs’ concentrations are assumed to decrease by moving from the tumor toward the depth of the phantom through a suggested pattern. The MCNPX Monte Carlo code is used for the simulations. Results The results show that for four concentrations tested, the dose enhancement factor in the shallower layer reaches 6, and decreases to 1.2 in the last layer. The dose enhancements are also examined for critical structures of the iris, cornea, sclera, and lens, showing maximum deviations of about 3 to 200% compared with the absence of GNPs in the healthy tissue. Considering the reported doses to the lens by clinical institutions, the effect of penetration of GNPs to deep layers on treatment time is also investigated. Conclusions The results show that the penetration of GNPs from the tumor toward healthy tissues strongly controls the dose enhancement over the various eye structures and emphasizes the importance of modeling the GNPs’ distribution in the medium on the overall dose enhancement. Considering the current challenges in the clinical use of GNPs, more effort needs to be made to reach an effective endpoint in treatment.

XMEA: A New Hybrid Diamond Multielectrode Array for the In Situ Assessment of the Radiation Dose Enhancement by Nanoparticles.

This work presents a novel multielectrode array (MEA) to quantitatively assess the dose enhancement factor (DEF) produced in a medium by embedded nanoparticles. The MEA has 16 nanocrystalline diamond electrodes (in a cell-culture well), and a single-crystal diamond divided into four quadrants for X-ray dosimetry. DEF was assessed in water solutions with up to a 1000 µg/mL concentration of silver, platinum, and gold nanoparticles. The X-ray detectors showed a linear response to radiation dose (r2 ≥ 0.9999). Overall, platinum and gold nanoparticles produced a dose enhancement in the medium (maximum of 1.9 and 3.1, respectively), while silver nanoparticles produced a shielding effect (maximum of 37%), lowering the dose in the medium. This work shows that the novel MEA can be a useful tool in the quantitative assessment of radiation dose enhancement due to nanoparticles. Together with its suitability for cells' exocytosis studies, it proves to be a highly versatile device for several applications.

Investigation of Tissue Components Impacts on Dose Enhancement Factor Using Monte Carlo Code

Despite the progress of science in cancer treatments and radiotherapy improvements, there are still several side effects that occur during tumors treatment, particularly on healthy tissues surrounded tumors. Newer treatment methods are being explored lately, one of which is the use of nanoparticles, wherein the tumor is injected with gold nanoparticles. Its aim is to enhance tumor sensitivity to radiation and reduce radiation damage to healthy tissues. Tissue type may play an effective role in enhancing the dose being received under the use of nanoparticles. This study aims to find the effect of different tissue components on dose enhancement factor through MCNP6 and GATE simulations, as well as to accurately compare the simulation results of these two code packages for dose enhancement factors. A 125I brachytherapy source was simulated in phantoms for five tissues or materials (adipose tissue, breast tissue, soft tissue, water, and brain tissue). MCNP6 simulation code was validated by comparing its results with a previous study by Cho et al. Gold nanoparticles were injected as a mixture at a concentration of 7 mg/g into tissues inside a tumor. MCNP6 and GATE simulation results were compared. It was estimated from MCNP simulations that the highest radiation dose enhancement of 2.34 occurs in adipose tissue while lowest dose enhancement of 1.69 is in brain. In comparison, from GATE results, the estimates were that the highest value of dose enhancement factor also occurred in adipose tissue at 2.01, and the lowest value in brain at 1.48. The comparison between two codes suggest that they are compatible with the percentage difference in all tissues being less than 15 %. This study confirms that both MCNP6 and GATE codes could calculate DEF for different tissues under irradiation from a low-energy source.

Utility of realistic microscopy-based cell models in simulation studies of nanoparticle-enhanced photon radiotherapy

To enhance the effect of radiation on the tumor without increasing the dose to the patient, the combination of high-Z nanoparticles with radiotherapy has been proposed. In this work, we investigate the effects of the physical parameters of nanoparticles (NPs) on the Dose Enhancement Factor (DEF), and on the Sensitive Enhancement Ratio (SER) by applying a version of the Linear Quadratic Model. A method for constructing voxelized realistic cell geometries in Monte Carlo simulations from confocal microscopy images was developed and applied to Gliobastoma Multiforme cell lines (U87 and U373). The comparison of simulations with realistic geometry and spherical geometry shows that there is significant impact on the survival curves obtained for the same irradiation conditions. Using this model, the DEF and the SER are determined as a function of the concentration, size and distribution of gold nanoparticles within the cell. For small NPs, d AuNP = 10 nm, no clear trend in the DEF and SER was observed when the number of NPs within the cell increases. Experimentally, the variable number of NPs measured inside the U373 cells (ranging between 1.48 × 105 and 1.19 × 106) also did not influence much the observed cell survival upon irradiation of the cells with a Co-60 source. The same lack of trend is obtained when the Au content in the cell is kept constant, 0.897 mg/g, but the size of the NPs is changed. However, if the number of NPs is kept constant (7.91 × 105) and the size changes, there is a critical diameter above which the dose effect increases significantly. Using the realistic geometries, it was verified that the key parameter for the DEF and the SER enhancement is the volume fraction of Au in the cell, with NP size being a more important parameter than the number of NPs.

The Effect of Dose Enhancement in Tumor With Silver Nanoparticles on Surrounding Healthy Tissues: A Monte Carlo Study.

Objectives: Cancer-related death rates account for approximately one-third of all deaths, and this rate is increasing remarkably every year. In this study, we examined the dose enhancement factor (DEF) in the tumor and surrounding tissues by adding different concentrations of silver nanoparticles (AgNPs) to the brain tumor using the Monte Carlo (MC) technique. Methods: This study used MCNP6.2 simulation software. A Planning Target Volume (PTV) of 1 × 1 × 1 cm3 was placed in the center of a cubic cranial model with dimensions of 5 × 5 × 5 cm3. Five different simulations were initially generated using the simple method. These simulations included pure PTV and PTV consisting of 4 different silver concentrations (5, 10, 20, and 30 mg/g). Additionally, a model was created using the nanolattice method, considering the size, position, and distribution of the AgNPs. Irradiation was performed using a source with a 6 MV linac photon spectrum. Measurements were performed using the *f8 tally, and DEF values were calculated. Results: In the simulation study using the simple method, the DEF value of PTV increased linearly with concentration, whereas the DEF values were lower than the simulation results with the nanolattice model (1.9 vs 1.4 for 30 mg/g NP concentration). Performing the simple method, we observed no remarkable dose increase in lateral OARs surrounding PTV. While a remarkable dose decrease was observed in distal OARs, a dose increase in the proximal OAR was observed, which was consistent with that of PTV. However, according to the results obtained by performing the nanolattice method, the dose increase was observed in both the proximal OAR and the distal OAR and was similar to that of PTV. Conclusion: While enhancing the dose in the tumor by adding NPs into the tumor, it is essential to consider whether it also increases the OAR dose. In addition, simulation studies on NPs showed that the dose increase varied significantly with particle size, position, and distribution. Hence, these factors should be considered carefully.

Nanoparticle-Mediated Radiotherapy: Unraveling Dose Enhancement and Apoptotic Responses in Cancer and Normal Cell Lines.

Cervical cancer remains a pressing global health concern, necessitating advanced therapeutic strategies. Radiotherapy, a fundamental treatment modality, has faced challenges such as targeted dose deposition and radiation exposure to healthy tissues, limiting optimal outcomes. To address these hurdles, nanomaterials, specifically gold nanoparticles (AuNPs), have emerged as a promising avenue. This study delves into the realm of cervical cancer radiotherapy through the meticulous exploration of AuNPs' impact. Utilizing ex vivo experiments involving cell lines, this research dissected intricate radiobiological interactions. Detailed scrutiny of cell survival curves, dose enhancement factors (DEFs), and apoptosis in both cancer and normal cervical cells revealed profound insights. The outcomes showcased the substantial enhancement of radiation responses in cancer cells following AuNP treatment, resulting in heightened cell death and apoptotic levels. Significantly, the most pronounced effects were observed 24 h post-irradiation, emphasizing the pivotal role of timing in AuNPs' efficacy. Importantly, AuNPs exhibited targeted precision, selectively impacting cancer cells while preserving normal cells. This study illuminates the potential of AuNPs as potent radiosensitizers in cervical cancer therapy, offering a tailored and efficient approach. Through meticulous ex vivo experimentation, this research expands our comprehension of the complex dynamics between AuNPs and cells, laying the foundation for their optimized clinical utilization.

Design of a novel nanoparticle to use X-ray fluorescence of TiO2 to induce photodynamic effects in the presence of PpIX

BackgroundRadiotherapy and photodynamic therapy are the methods of cancer treatment. Although one limitation of photodynamic therapy (PDT) is the limited penetration depth of light through tissue, using X-rays does not have this restriction. Self-lighting nanoparticles can convert X-rays into UV/visible. This study focuses on a newly designed nanostructure containing mesoporous silica nanoparticles (MSN), titanium dioxide nanoparticles (TiO2, anatase grade), and protoporphyrin IX (PpIX) as a photosensitizer to overcome the limitations of photodynamic therapy. MethodsAfter the synthesis and characterization of Ti-MSN/PpIX@PVP nanostructure, two ROSes (OH* and 1O2) were measured when the nanostructures were irradiated with 100 kV and 6 MV photons. The toxicity of Ti-MSN/PpIX@PVP nanostructure in presence and absence of radiation was investigated on DFW and HT-29 cell lines. The in-vitro experiments were analyzed using the MTT assay and colony count assay. Finally, the effect of light exposure in the presence of Ti-MSN/PpIX@PVP nanostructure on the two cell lines was studied. The in-vitro studies were evaluated using the Synergism Index (Syn) and Dose Enhancement Factor (DEF). ResultsBased on the FESEM (field emission scanning electron Microscopy) images and DLS (dynamic light scattering) measurements, the size of Ti-MSN/PpIX nanostructure was determined as (35.2 nm) and (168.4 nm), respectively. Based on the spectrofluorimetry results, 100 kV photons produced more ROSes than 6 MV photons. The results of MTT assay and colony formation for X-PDT show Syn >1, except for 100 kV photons for HT-29 cell line. The nanostructure also reduced colony formation induced by X-PDT more effectively when irradiated by 100 kV photons on DFW cells. The results obtained from conventional PDT showed that the ED 50 of the HT-29 cell line was 6 times higher than that of the DFW cell line. ConclusionDesigning and synthesizing Ti-MSN/PpIX@PVP nanostructures offer a promising strategy for reducing the current challenges in PDT and for developing and advancing X-PDT as an innovative cancer treatment technique.

Assessment of dosimetric sensitivity enhancement of xylenol orange Fricke gel by AuNPs: optical and MR imaging investigation

Metallic nanoparticles, such as gold (Au, Z = 79) and silver (Ag, Z = 47) nanoparticles (AuNPs and AgNPs, respectively), possess strong surface plasmonic resonance (SPR) and high atomic number, which makes them ideal candidates for enhancing dosimeter sensitivity. In this study, we have inserted different mass percentages (from 0 to 0.015 wt%) of AuNPs into a gelatinous Fricke-xylenol-orange (FXO-f) gel matrix and irradiated it with doses ranging from 2 to 32 Gy, using a source of x-ray of low energy with an effective energy of 42 keV. Optical absorption increased significantly; sensitivity gains of up to 50% were achieved for the FXO-f gel matrix containing 0.011 wt% AuNPs. To elucidate the mechanism underlying this increased sensitivity, we also evaluated FXO-f gel matrixes containing AgNPs. AgNPs insertion into the FXO-f gel matrix did not enhance sensitivity, which suggested that the AgNPs plasmonic absorption band and the FXO-f gel matrix absorption band at 441 nm overlapped, to increase absorption even after the gel matrix was irradiated. To visualize the dose distribution, we recorded optical tomography and acquired 3D reconstruction maps. In addition, we analyzed the dose enhancement factor (DEF) by using magnetic resonance images. AuNPs insertion into the FXO-f gel matrix resulted in a DEF gain of 1.37, associated with the photoelectric effect originating from the increased number of free radicals.

Olaparib enhances sensitization of BRCA-proficient breast cancer cells to x-rays and protons.

This study aimed to compare the radiosensitizing effect of the PARP inhibitor, Olaparib, between proton and X-rays irradiations in BRCA-proficient breast cancer (BC) cells. Two BRCA-proficient BC cell lines, MDA-MB-231 and T47D BC, were used. Cell proliferation was assessed using the CCK-8 assay, and radiosensitivity was determined through the clonogenic survival assay. Flow cytometry was employed to analyze cell cycle distribution and apoptosis. The kinetics of DNA damage repair were evaluated using γH2AX immunofluorescence imaging and the comet assay. Tumor spheroid assays were conducted to test radiosensitivity in a three-dimensional culture condition. Olaparib sensitized both MDA-MB-231 and T47D cells to proton and X-ray irradiation in the clonogenic assay. MDA-MB-231 cells exhibited a higher dose enhancement factor for Olaparib than T47D cells. Olaparib increased radiation-induced G2/M cell cycle arrest and apoptosis specifically in MDA-MB-231 cells. γH2AX immunostaining and the comet assay showed Olaparib augmented radiation-induced DNA damage and apoptosis. The enhancement effect of Olaparib was more pronounced in proton irradiation than in X-ray irradiation, particularly in MDA-MB-231 cells than T47D cells. Both radiation and Olaparib dose-dependently inhibited spheroid growth in both cell lines. The synergy scores demonstrated that Olaparib interacted more strongly with protons than X-rays. The addition of an ATR inhibitor further enhanced Olaparib-induced proton radiosensitization in MDA-MB-231 cells. This study found that Olaparib enhanced radiation efficacy in BRCA-proficient breast cancer cells, with a more pronounced effect observed with proton irradiation compared to X-ray irradiation. Combining Olaparib with an ATR inhibitor increased the radiosensitizing effect of protons.

Evaluate the effects of kilovoltage transmission target X-ray equipment combined with radiosensitizers for Auger electron radiotherapy

Auger electrons are well-suited for targeted radiotherapy due to their ability to transfer high energy over short distances. Auger radiotherapy can be achieved by utilizing the characteristic radiation of transmission X-ray tubes and radiosensitizers to generate numerous Auger electrons. In this study, the Monte Carlo N-Particle (MCNP6) code was employed to simulate the deposition of dose in cells when combining the transmission X-ray tube with various concentrations of radiosensitizers. The results reveal that when the transmission X-ray tube is combined with 70 mg of gold nanoparticles (GNPs), the photoelectron flux is 1.16 × 103 (particles/cm2), which is 3.86 times higher than that observed with 0 mg of GNPs. Furthermore, the Auger electron flux is 3.51 × 102 (particles/cm2), representing a 15.51-fold increase compared to 0 mg of GNPs. The corresponding dose enhancement factor (DEF) is 3.14, representing the most substantial proportional increase observed. This study suggests that the combination of a transmission X-ray tube with appropriate radiosensitizers and concentrations can generate a significant number of photoelectrons and Auger electrons, resulting in a notable radio-enhancing effect. This innovative approach holds promise for the development of Auger radiotherapy as a potential therapeutic process. Future investigations could explore the optimal combination of transmission X-ray tubes and radiosensitizers to further advance the applications of Auger radiotherapy.

Radiosensitization of Glioblastoma Using Targeted Inhibition of N-Myristoylation

Treating Glioblastoma remains a major challenge. Radiotherapy has a long-standing role in extending survival, but almost all tumors are expected to recur and be fatal. Historic dose-escalation studies do not yield additional benefit beyond the current 60 Gy dose. Further therapeutic improvement can be gained with radiosensitizers. An undiscovered potential radiosensitization approach may exist in inhibiting the N-myristoylation pathways upregulated in malignant cells. Inhibiting this pathway has been shown to have pleotropic effects including decreasing PARP-1 activity and other cancer-driving pathways that may synergize with radiotherapy. This is a first report in using a targeted N-myristoyltransferase (NMT) inhibitor as a radiosensitizer in glioblastoma. Immortalized glioma cell lines (U87 and U251) and patient-derived de novo (ED501) and post-chemoradiation recurrent (ED512) cell lines were used to a NMT1/2 inhibitor with radiotherapy. Cell surface expression levels for NMT1 and NMT2 were established using immunofluorescence microscopy. In vitro cell viability studies via mitochondrial reduction of resazurin dye and clonogenic assays were done with single fraction 2 & 4 Gy irradiation with 5 days of drug exposure (5-150 nM 3 days prior to irradiation and 2 days post) to account for drug pharmacodynamics. PARP-1 expression by western blot was tested with exposure to drug and/or radiation. Whole exome sequencing and methylation profiling were done to find predictive markers of radiosensitization. Preliminary results show significant radiosensitization effect with a dose enhancement factor ranging from 1.33 to 2.71x higher than radiation alone. The amount of radiosensitization varied per cell line, with U251 and ED512 being more sensitive. The cell line sensitivity was not reliably predicted by the NMT cell surface receptor expression. PARP-1 activity increased with radiotherapy but was inhibited with drug exposure. Exome sequencing showed the radiosensitizing effect correlated with mutations in DNA damage repair and myristoylation pathways. N-myristoylation inhibition appears to be a novel method of radiosensitization for glioblastoma. N-myristoylation affects multiple oncogenic pathways including PARP-1 downregulation, which impedes DNA damage repair and may be what leads to radiosensitization. Future studies are aimed at further predictive markers and in vivo efficacy.

Technical note: Evaluation of the dose enhancement effect for a novel transmission-type x-ray tube using the Monte Carlo method.

Transmission-target x-ray tubes generate more x-rays than reflection thick-target x-ray tubes. A transmission x-ray tube combined with radiosensitizers has a better radiation enhancement effect. This study investigated the feasibility of using a transmission x-ray tube with radiosensitizers in clinical radiotherapy and its effect on radiation dose enhancement. This study used MCNP6.2 to simulate the model of a transmission x-ray tube and Co-60 beam. The radiation enhancement effect of radiosensitizers was examined with iodine-127 (I-127), radioiodinated iododeoxyuridine (IUdR), and gold nanoparticles (GNPs). The study results showed that the dose enhancement factor (DEF) of the transmission x-ray tube with GNPs was 10.27, which was higher than that of I-127 (6.46) and IUdR (3.08). The DEF of the Co-60 beam with GNPs, I-127, and IUdR was 1.23, 1.19, and 1.2, respectively. The Auger electron flux of the transmission x-ray tube with GNPs was 1.19E+05 particles/cm2 . This study found that a transmission x-ray tube with appropriate radiosensitizers could produce a high rate of Auger electrons to fulfill the radiation enhancement effect, and this procedure has the potential to become a radiotherapy modality.