High Atomic Number Elements Research Articles

One Pot Synthesis of PEGylated Bimetallic Gold-Silver Nanoparticles for Imaging and Radiosensitization of Oral Cancers.

BackgroundRadiotherapy is an important treatment modality for many types of head and neck squamous cell carcinomas. Nanomaterials comprised of high atomic number (Z) elements are novel radiosensitizers enhance radiation injury by production of free radicals and subsequent DNA damage. Gold nanoparticles are upcoming as promising radiosensitizers due to their high (Z) biocompatibility, and ease for surface engineering. Bimetallic nanoparticles have shown enhanced anticancer activity compared to monometallic nanoparticles.Materials and MethodsPEG-coated Au–Ag alloy nanoparticles (BNPs) were synthesized using facile one pot synthesis techniques. Size of ~50±5nm measured by dynamic light scattering. Morphology, structural composition and elemental mapping were analyzed by electron microscopy and SAXS (small-angle X-ray scattering). The radiosensitization effects on KB oral cancer cells were evaluated by irradiation with 6MV X-rays on linear accelerator. Nuclear damage was imaged using confocal microscopy staining cells with Hoechst stain. Computed tomography (CT) contrast enhancement of BNPs was compared to that of the clinically used agent, Omnipaque.ResultsBNPs were synthesized using PEG 600 as reducing and stabilizing agent. The surface charge of well dispersed colloidal BNPs solution was −5mV. Electron microscopy reveals spherical morphology. HAADF-STEM and elemental mapping studies showed that the constituent metals were Au and Ag intermixed nanoalloy. Hydrodynamic diameter was ~50±5nm due to PEG layer and water molecules absorption. SAXS measurement confirmed BNPs size around 35nm. Raman shift of around 20 cm−1 was observed when BNPs were coated with PEG. 1H NMR showed extended involvement of −OH in synthesis. BNPs efficiently enter cytoplasm of KB cells and demonstrated potent in vitro radiosensitization with enhancement ratio ~1.5–1.7. Imaging Hoechst-stained nuclei demonstrated apoptosis in a dose-dependent manner. BNPs exhibit better CT contrast enhancement ability compared to Omnipaque.ConclusionThis bimetallic intermix nanoparticles could serve a dual function as radiosensitizer and CT contrast agent against oral cancers, and by extension possibly other cancers as well.

Development of high-density radiation shielding materials containing BaSO4 and investigation of the gamma-ray attenuation properties

The high-density shielding materials containing higher percentage (>80%) of BaSO4 have been developed and their gamma-ray attenuation parameters have been investigated. Three samples have been prepared [Sample-1 (83.75%), Sample-2 (84.75%), and Sample-3 (82.75%)], their elemental composition has been determined by the EDX method, and the density has been measured experimentally for Sample-1 (3.362 g/cm3), Sample-2 (3.365 g/cm3), and Sample-3 (3.358 g/cm3). The mass attenuation coefficients (μ/ρ) have been calculated analytically in order to generate a database for the photon energy range from 1keV to 100MeV using WinXcom software. For validation, this parameter has been measured experimentally for gamma-ray emitted from 133Ba radioactive sources using HPGe detector (with relative efficiency ≈20% relative to a 3"×3"NaI(Tl) detector, and resolution 2.3keV at 1.33MeV γ-lines). The linear attenuation coefficient (μ), total atomic cross section (σa), total electronic cross section (σe), effective atomic number (Zeff), effective electron density (Neff), and relaxation length (λ) have been calculated for the same energy range. All parameters have been compared with the values for five different concretes namely barite, serpentine, ilmenite-magnetite, ordinary concrete, and basalt-magnetite. Transmission graphs have been drawn for some widely used radioactive sources. Sample-2 with the highest density (3.365 g/cm3) and comprising relatively higher atomic number elements is found to be the most effective shield for gamma-ray attenuation.

Optimization of Plastic Scintillator for Detection of Gamma-Rays: Simulation and Experimental Study

Plastic scintillators are widely used in various radiation measurement applications, and the use of plastic scintillators for nuclear applications including decommissioning, such as gamma-ray detection and measurement, is an important concern. With regard to efficient and effective gamma-ray detection, the optimization for thickness of plastic scintillator is strongly needed. Here, we elucidate optimization of the thickness of high-performance plastic scintillator using high atomic number material. Moreover, the EJ-200 of commercial plastic scintillators with the same thickness was compared. Two computational simulation codes (MCNP, GEANT4) were used for thickness optimization and were compared with experimental results to verify data obtained by computational simulation. From the obtained results, it was confirmed that the difference in total counts was less than 10% in the thickness of the scintillator of 50 mm or more, which means optimized thickness for high efficiency gamma-ray detection such as radioactive 137Cs and 60CO. Finally, simulated results, along with experimental data, were discussed in this study. The results of this study can be used as basic data for optimizing the thickness of plastic scintillators using high atomic number elements for radiation detection and monitoring.

Trace element imbalances in blood serum of Alzheimer’s disease patients

Trace element concentration of blood serum samples of patients afflicted with Alzheimer’s disease and controls were determined using inductively coupled plasma-mass spectrometry. 22 elements starting from low atomic number element lithium to high atomic number element lead were covered under this study. The concentration of lithium and vanadium were measured for the first time. The concentration levels of lithium, aluminum, vanadium, chromium, manganese, iron, cobalt, nickel, zinc, arsenic, selenium, silver, cadmium, cesium, mercury, and lead are found to be higher and the concentration levels of gallium, rubidium, and barium to be lower in the samples of the Alzheimer’s disease afflicted patients compared to controls. The difference in the concentration levels of beryllium, copper, and strontium between the specimens of Alzheimer's disease patients and controls is statistically insignificant. An attempt is made to correlate the trace element imbalance, where observed, with the etiology and pathogenesis of Alzheimer’s disease.

The dependence of radio-sensitization efficiency on mitochondrial targeting with NaGdF4:Yb,Er nanoparticles

Radio-sensitization is highly desired to reduce side-effect of the harsh dose of radiation therapy (RT), for which nanoparticles with high atomic number elements provide a promising tool. However, insufficient knowledge on utilizing the interaction between nanoparticles and cancerous cells hampers the improvement of therapeutic outcome. We herein employed NaGdF4:Yb,Er nano-crystals as the sensitizer, and modified them with a tumor targeting agent and a mitochondria targeting moiety, separately and jointly, to achieve varied extent of mitochondrial accumulation. We observed that NaGdF4:Yb,Er nano-crystal, even unmodified with targeting ligands, is effective for radio-sensitization. Furthermore, the extent of mitochondrial targeting was responsible for sensitization efficiency both in vitro and in vitro. By RNA sequencing technique, the result was ascribed to the reactive oxygen species (ROS) mediated TNF-JNK pathway and cell cycle arrest besides breaking DNA, in contrast to only DNA damage only with those untargeted nanoparticles. Our work indicated that ROS generated by the irradiation can be utilized by activating an alternative apoptotic pathway with mitochondrial targeting nanoparticles, and therefore may suggest an approach for the enhancement of radio-sensitization. Statement of significanceRadiosensitization by nanoparticles could reduce the burden of cancer due to lowering the dose of radiation therapy and reducing side-effect. How to fully utilize the interactions of irradiation-nanoparticles-biotissues remains a challenge for improving the outcome of radiosensitization. In this manuscript, by modifying tumor-targeting and mitochondria-targeting ligands on nanoparticles, separately and jointly, we demonstrated that the radiosensitization efficiency of NaGdF4:Yb,Er nanoparticle depends on the extent of accumulation near mitochondria. By RNA-seq technique, the RT sensitization with mitochondrial targeting was ascribed to ROS-mediated TNF-JNK pathway and cell cycle arrest, in contrast to only DNA breaks with untargeted nanoparticles. The results suggested a strategy for better utilization of the energy of therapeutic irradiation and demonstrate that subcellular targeting is a potent factor for designing nanoparticulate radiosensitizers.

Development of X-ray contrast agents using single nanometer-sized gold nanoparticles and lactoferrin complex and their application in vascular imaging

The technology to accurately image the morphology of tumor vessels with X-ray contrast agents is important to clarify mechanisms underlying tumor progression and evaluate the efficacy of chemotherapy. However, in clinical practice, iodine-based contrast agents present problems such as short blood retention owing to a high clearance ability and insufficient X-ray absorption capacity when compared with other high atomic number elements. To resolve these issues, gold nanoparticles (AuNPs), with a high atomic number, have attracted a great deal of attention as contrast agents for angiography, and have been employed in small animal models. Herein, we developed novel contrast agents using AuNPs and captured changes in tumor vessel morphology with time using X-ray computed tomography (CT). First, glutathione-supported single nanometer-sized AuNPs (sAu/GSH) (diameter, 2.2 nm) were fabricated using tetrakis(hydroxymethyl)phosphonium chloride as a reducing agent. The sAu/GSH particles were intravenously injected into mice, remained in vessels for a few minutes, and were then excreted by the kidneys after 24 h, similar to the commercial contrast agent iopamidol. Next, the Au/GSH and lactoferrin (sAu/GSH-LF) (long axis size, 17.3 nm) complex was produced by adding lactoferrin to the sAu/GSH solution under the influence of a condensing agent. On intravenously administering sAu/GSH-LF to mice, the blood retention time was 1−3 h, which was considerably longer than that observed with iopamidol and sAu/GSH. Moreover, we succeeded in imaging morphological changes in identical tumor vessels for several days using X-ray CT with sAu/GSH-LF.

Radiosensitization With Nanoparticles Targeting to Mitochondria

Sensitizing radiation therapy (RT) for cancer is highly desired to reduce side-effect of the harsh dose of irradiation, and nanoparticles with high atomic number elements provide a promising tool. However, insufficient knowledge on utilizing the interaction between nanoparticles and cancerous cells hampers the improvement of therapeutic outcome. We herein employed NaGdF4:Yb,Er nanocrystals as the sensitizer, and modified them with a tumor targeting agent and a mitochondria targeting moiety, separately and jointly, to achieve varied extent of mitochondrial accumulation. We observed that NaGdF4:Yb,Er nanocrystal, even unmodified with targeting ligands, is effective for radiosensitization. Furthermore, the extent of mitochondrial targeting was responsible for sensitization efficiency both in vitro and in vivo. By RNA sequencing (RNA-seq) technique, the result was ascribed to the reactive oxygen species (ROS) mediated TNF-JNK pathway and cell cycle arrest, rather than breaking DNA with those untargeted nanoparticles. Our work indicated that ROS generated by the irradiation can be utilized by activating an alternative apoptotic pathway with mitochondrial targeting nanoparticles, and therefore may suggest an approach for the enhancement of radiosensitization.

Synthesis and characterization of gadolinium-decorated [60]fullerene for tumor imaging and radiation sensitization

Purpose The excellent contrast of high atomic number (Z) elements compared to soft tissues has advanced their use as contrast agents for computed tomographic imaging and as potential radiation sensitizers. We evaluated whether gadolinium (Gd) could serve as such a theranostic agent for high-resolution magnetic resonance imaging (MRI) due to its paramagnetic properties and radiosensitization due to its high Z. Materials and methods To improve the relaxivity of Gd, we coupled it to [60]fullerene, an elemental carbon allotropic nanoparticle that seamlessly traverses physiological barriers . By adding serinol, an aliphatic alcohol derived from amino acid serine, we turned [60]fullerene, which is otherwise insoluble in water, into a highly water-soluble derivative and decorated it externally with a payload of chelated gadolinium ions. Results When [60]fullerene was functionalized in this manner with two gadolinium ions (Gd2C60), it displayed considerably higher T1 relaxivity at 4.7 T than the commercially used MRI contrast agent, Magnevist, (18.2 mM−1s−1 vs. 4.7 mM−1s−1). Attempts to increase this even further via decoration of [60]fullerene with 12 gadolinium ions was unsuccessful due to a poor water solubility. However, the current formulation of Gd2C60 did not result in any appreciable radiosensitization. Conclusion Our results show a successful generation of a novel contrast agent via decoration of fullerene with two chelated Gd ions. Though this formulation was not successful in generating radiosensitization, other chemical modifications can be further explored to increase radiosensitization potential.

Halide perovskites: A dark horse for direct X‐ray imaging

AbstractThe high cost and difficulty of fabricating high‐quality, thick, large‐area X‐ray absorbers limit their widespread applications in flat‐panel direct hard X‐ray imaging. Then it comes to the recently rising halide perovskites, which show large carrier mobility and lifetime, contain high atomic number elements and are solution processible, making them ideal for large‐area direct hard X‐ray imaging. Over the past few years, direct X‐ray detectors based on a variety of perovskites have been developed, showing impressive progress in achieving high sensitivity and low detection limit. Alongside the developments, the underlying correlations between the intrinsic properties of the perovskites and their X‐ray detection performance have been intensively studied, providing valuable information to tackle the remaining challenges, such as large dark current, baseline drifting and so forth. However, it is surprising to find that there have been no efforts to bring together a comprehensive review and comparative analysis on these previous research endeavors, and some general principles and guidelines of engineering the perovskites toward advanced X‐ray detectors have yet to be creamed off. Here, recent advances in engineering perovskites for direct X‐ray detection are reviewed in the hope of providing fundamental understanding of this fast‐developing field. First, the operation principles of direct X‐ray detectors targeting flat‐panel X‐ray imaging will be introduced, particularly relevant to perovskite materials. Then, recent innovative works regarding the preparation and manipulation of single‐crystalline and poly‐crystalline perovskites are discussed in detail, through which specific effects of the intrinsic properties of the perovskite upon X‐ray detection are highlighted. This is followed by a summary of the review and outlook of future directions.image

Origin of ultra-wide IR transmission and ultra-large birefringence of mercurous halide series with one dimensional chain-like structure: An ab initio study

Mercurous halide single crystals with one-dimensional chain-like structure exhibit great potential as polarizers or acousto-optic devices in infrared range based on the ultra-large birefringence and ultra-wide infrared transmission range. However, the origin of these two unique properties of mercurous halide families are unclear. Herein, we theoretically investigate the electronic and vibrational properties of these analogues through first principle calculation to explore the origin of these two distinct properties. The short cut-on wavelength is due to the large bandgap stemming from the ability of halogen to bind valence electrons tightly, while the long wavelength infrared cut-off originates from low phonon frequency caused by the high atomic weight of Hg and halogen atoms. Attributed to the high covalent characteristic between Hg and halogen atoms along c orientation and the very weak van der Waals force between X-Hg-Hg-X (X = Cl, Br, I) molecules perpendicular to c orientation, mercurous halide crystals exhibit large anisotropy of polarization leading to the large birefringence. Our analysis reveals that both one-dimensional chain structure and high atomic number elements contribute to the large birefringence and wide infrared transparent range, which would inspire a direction for designing new high-performance infrared polarizing materials.

Crystal Chemical Characterisation of Red Beryl by ‘Standardless’ Laser‐Induced Breakdown Spectroscopy and Single‐Crystal Refinement by X‐Ray Diffraction: An Example of Validation of an Innovative Method for the Chemical Analysis of Minerals

Laser‐induced breakdown spectroscopy (LIBS) is a valuable technique for performing qualitative and quantitative chemical determinations of all elements in one shot, including low atomic number elements such as Li and Be. This technique does not require any sample preparation to reveal the atomic species, even when present in trace amounts (< 0.01% m/m). In this study, for the first time, we provide an accurate mineral formula for a Cs‐rich red beryl by combining crystallographic data obtained using the traditional single‐crystal X‐ray diffraction technique and quantitative chemical data obtained with an innovative ‘standardless’ method: Calibration‐free‐LIBS (CF‐LIBS). In particular, a new LIBS prototype coupled with a petrographic microscope (CF‐μLIBS) was used to analyse chemically homogeneous areas of about 10 μm spot size, causing minimal damage to the mineral. The results showed that calibration‐free quantitative analysis is suitable for the quantification of major and minor low and high atomic number elements in beryl. The accuracy of quantification of low atomic number elements by CF‐μLIBS led to the empirical formula: [12](Cs0.006Na0.019K0.017Ca0.019)Σ0.061 [4](Be2.989Li0.011)Σ3.000 [6](Ti0.053Mn0.051Mg0.007Al1.890)Σ2.000 [4](Be0.116Fe0.024Si5.860)Σ6.000 O18. This formula is consistent with the crystal‐structure refinement data and demonstrates the validity of CF‐μLIBS for chemical analyses of minerals containing low atomic number elements.

Improving signal-to-noise ratio for the forensic analysis of glass using micro X-ray fluorescence spectrometry.

Micro X-ray fluorescence spectrometry (μXRF) is a standard technique used for the elemental analysis of glass fragments in forensic casework. The glass specimens encountered in casework are usually small (<1 mm), thin fragments that are partially transparent to the exciting X-ray beam. In addition to providing fluorescence from the small glass fragments, the primary beam X-rays can scatter within the chamber and provide noise in the measurements. To reduce scatter from the sample stage, the fragments are typically mounted on a thin plastic film and raised on an XRF sample cup (≤3 cm in height). However, at these heights, there may still be significant scatter from the sample stage, which adversely affects the signal-to-noise ratio (SNR) and the limit of detection (LOD). A plastic mount was designed and 3D-printed in-house to allow fragments to be raised as high as possible from the sample stage, thereby minimizing stage scatter. Most elements detected in glass showed an improvement in the SNR when using the 3D-printed mount for analyses. The greatest improvement (>30%) was observed for lower atomic number elements (Na and Mg) and higher atomic number elements (Sr and Zr). Another simple method to improve SNR is the use of primary beam filters; when using primary beam filters during analyses, elements with characteristic lines in the high-energy range (Rb, Sr, and Zr) showed the greatest improvement (>70%) in SNR. The impact of both strategies for the improvement of SNR is presented here.

Giant momentum-dependent spin splitting in centrosymmetric low- Z antiferromagnets

The energy vs. crystal momentum E(k) diagram for a solid (band structure) constitutes the road map for navigating its optical, magnetic, and transport properties. By selecting crystals with specific atom types, composition and symmetries, one could design a target band structure and thus desired properties. A particularly attractive outcome would be to design energy bands that are split into spin components with a momentum-dependent splitting, as envisioned by Pekar and Rashba [Zh. Eksperim. i Teor. Fiz. 47 (1964)], enabling spintronic application. The current paper provides "design principles" for wavevector dependent spin splitting (SS) of energy bands that parallels the traditional Dresselhaus and Rashba spin-orbit coupling (SOC) - induce splitting, but originates from a fundamentally different source -- antiferromagnetism. We identify a few generic AFM prototypes with distinct SS patterns using magnetic symmetry design principles. These tools allow also the identification of specific AFM compounds with SS belonging to different prototypes. A specific compound -- centrosymmetric tetragonal MnF2 -- is used via density functional band structure calculations to quantitatively illustrate one type of AFM SS. Unlike the traditional SOC-induced effects restricted to non-centrosymmetric crystals, we show that antiferromagnetic-induced spin splitting broadens the playing field to include even centrosymmetric compounds, and gives SS comparable in magnitude to the best known ('giant') SOC effects, even without SOC, and consequently does not rely on the often-unstable high atomic number elements required for high SOC. We envision that use of the current design principles to identify an optimal antiferromagnet with spin-split energy bands would be beneficial for efficient spin-charge conversion and spin orbit torque applications without the burden of requiring compounds containing heavy elements.

Advanced X-ray Shielding Materials Enabled by the Coordination of Well-Dispersed High Atomic Number Elements in Natural Leather.

Nowadays, X-rays are playing increasingly important roles in daily life and industrial manufacture, which calls for effective and mobile shielding materials. However, it seems to be a paradox to prepare shielding materials simultaneously achieving excellent X-ray attenuation properties and superior mechanical strength. Here, an advanced leather-based X-ray shielding material containing bismuth and iodine (BiINP-LM) is prepared, and the stable and well-dispersed loading of high-Z element components is enabled by favorable interactions between bismuth iodide and leather, i.e., coordination, hydrogen bonds, and electrostatic attractions. A piece of BiINP-LM with 1.00 mm thickness displays an excellent X-ray attenuation efficiency of more than 90% in the photon energy range below 50 keV and 65% at 83 keV, which averagely exceeds ∼3% than that of the 0.25 mm lead plate and ∼5% than that of the 0.65 mm commercial lead apron. Additionally, the coordination between bismuth and leather provides an enhanced tensile and tear strength of ∼10-fold and 3-fold compared with the lead apron. It is worth mentioning that BiINP-LM also displays extra high water-vapor permeability, which is ∼50-fold more than the lead apron. Overall, this work opens up a new prospect for preparing advanced X-ray shielding materials with both excellent X-ray attenuation and outstanding physiomechanical performances.

Flexible Inkjet-Printed Triple Cation Perovskite X-ray Detectors.

Flexible direct conversion X-ray detectors enable a variety of novel applications in medicine, industry, and science. Hybrid organic-inorganic perovskite semiconductors containing elements of high atomic number combine an efficient X-ray absorption with excellent charge transport properties. Due to their additional cost-effective and low-temperature processability, perovskite semiconductors represent promising candidates to be used as active materials in flexible X-ray detectors. Inspired by the promising results recently reported on X-ray detectors that are based on either triple cation perovskites or inkjet-printed perovskite quantum dots, we here investigate flexible inkjet-printed triple cation perovskite X-ray detectors. The performance of the detectors is evaluated by the X-ray sensitivity, the dark current, and the X-ray stability. Exposed to 70 kVp X-ray radiation, reproducible and highly competitive X-ray sensitivities of up to 59.9 μC/(Gyaircm2) at low operating voltages of 0.1 V are achieved. Furthermore, a significant dark current reduction is demonstrated in our detectors by replacing spin-coated poly(3,4-ethylenedioxythiophene)/poly(styrenesulfonate) (PEDOT:PSS) with sputtered NiOx hole transport layers. Finally, stable operation of a flexible X-ray detector for a cumulative X-ray exposure of 4 Gyair is presented, and the applicability of our devices as X-ray imaging detectors is shown. The results of this study represent a proof of concept toward flexible direct conversion X-ray detectors realized by cost-effective and high-throughput digital inkjet printing.

Joint Optimization of Collimator and Reconstruction Parameters in X-Ray Fluorescence Computed Tomography Using Analytical Point Spread Function and Model Observer.

To jointly optimize collimator design and image reconstruction algorithm in X-ray Fluorescence Computed Tomography (XFCT) for imaging low concentrations of high atomic number (Z) elements in small animal models. Single pinhole (SPH) collimator and three types of multi-pinhole (MPH) collimators were evaluated. MPH collimators with 5, 7, and 9 pinholes using lead, stainless steel and brass were considered. A digital cylindrical phantom (0.5mm3 voxels) of 25mm diameter and 25mm height with a central 5mm diameter and 12.5mm height cylindrical insert containing gold nanoparticles (2:1 insert: background concentration) was modeled. A 125kVp, 2mm Sn filtered x-ray spectrum (0.5 cGy/projection) for gold K-shell XFCT was considered. System matrices were implemented using analytical point spread functions (PSF) for each pinhole collimator. Poisson noise was added to the projection data (16 equiangular views) before image reconstruction using Maximum-Likelihood Expectation-Maximization (ML-EM) algorithm. Signal-present and signal-absent images were generated for the detection task performed by a channelized Hotelling observer (CHO) with 10 Dense Difference-of-Gaussian channels. The area under the curve (AUC) in receiver operating characteristic was used as the image quality metric. A stainless steel focusing type MPH with 7 pinholes and 20 iterations of ML-EM provided the highest AUC. MPH collimators outperformed SPH collimators for XFCT and consistently high AUCs were observed with focusing type MPH designs with 7 pinholes. The combinations of collimator design and image reconstruction parameters that maximized AUC were identified, which could improve the performance of XFCT.

The feasibility of NaGdF4 nanoparticles as an x-ray fluorescence computed tomography imaging probe for the liver and lungs.

As a novel imaging modality, x-ray fluorescence computed tomography (XFCT) can provide distribution and concentration information of contrast agents containing high atomic number elements, such as iodine, gadolinium, barium, gold, and platinum. Since XFCT has a better sensitivity and detection limit of high-Z elements compared with traditional and spectral CT, it becomes a powerful quantitative imaging tool for biological studies. The main problem of current XFCT imaging is its low emission and detection efficiency of x-ray fluorescence (XRF) photons. Increasing XRF photons generation by choosing a high atomic element as a contrast agent is essential to improve the imaging quality of XFCT. Gadolinium emits at least a few times more of XRF photons than gold under the same x-ray excitation condition, leading to a detection limit at a level of sub-mg/mL as the next generation of clinical imaging modality. However, most current XFCT studies have utilized gadolinium salt as the contrast agent, which could not accumulate in organs or tumors efficiently, making in vivo XFCT imaging quite difficult. In this study, we present NaGdF4 nanoparticles with ultra-small size as nanoprobes to test the feasibility for in vivo XFCT application for the first time. NaGdF4 nanoparticles with different sizes (3-10nm) were successfully synthesized via a coprecipitation process by controlling the reaction time at temperature of 290 °C. The morphology, crystal phase, chemical composition, and size of such NPs were further characterized with HR-TEM, XRD, and EDX. The abilities of XRF photons from different sizes of NPs were quantified by our customized XFCT imaging system. To access the in vivo application of as-synthesized NPs, such hydrophobic NPs capped OA molecules were further modified with AEP via a ligand-exchange process and characterized with FT-IR. For in vivo XFCT imaging, 0.1mL of 30mg/mL NPs were injected into nude mice via the tail vein. The Varian G-297 x-ray tube was set to 150kV and 0.5mA. The XRF photons were captured by a Kromek eV-3500 photon counting detector at each 8° for 10s. The successfully synthesized NaGdF4 nanoparticles (3-10nm) were monodisperse, highly uniform spherical morphology and hexagonal crystalline phases. No significant influence on XRF photons yields or XFCT imaging quality were found by varying the nanoparticle size. The XRF photons were 2.5 times more emitted from NaGdF4 nanoparticles (NPs) compared to gold nanoparticles, thereby leading to a better image quality. With the AEP surface modification, such NPs were readily adapted for use in in vivo XFCT applications with monodispersity in aqueous solution and negligible cytotoxicity. With the tail-vein injection, the liver, spleen, and lungs could be clearly imaged with XFCT at a sub-mg/mL level. Such NaGdF4 NPs, which were synthesized with coprecipitation process, were modified with AEP for in vivo XFCT applications. With both the phantom and in vivo experiments, such NPs were proved to be appropriate probes for XFCT application with the detection limit at a sub-mg/mL level. In the future research, such NPs could be further functionalized with targeting molecules for early-phase cancer detection.

A Comparative Study of Photo-Neutron Production from Flattened and Unflattened Beams in a Medical Linear Accelerator

High energy x-rays from a medical linear accelerator (LINAC) is used to treat cancer patients in radiotherapy department. The medical linac can produce bremsstrahlung x-rays from 4MV to 18MV and the commonly used linac produces 6MV, 10 MV and 15MV photons for treating major parts of the cancer patients. The photo neutron production during the radiation treatment is one of the major issues which have to be addressed with high impact because of the high LET nature associated with it. Photo neutrons are produced from several high atomic number (Z) elements present in the linac head mostly by the (ɣ, n) reaction. The flattening filter used in medical linac to produce uniform intensity distribution (made up of either tungsten, steel, lead, uranium, aluminum or a combination) is one of the photo neutron sources in the linac head. Advanced radiotherapy treatments like Intensity Modulated Radiotherapy (IMRT) and Volumetric Arc Therapy (VMAT) doesn't require a flat radiation field, and hence the flattening filter could be removed. This is called flattening filter free beam (FFF beam)1, 2. The removal of the filter will result in a forward peaked photon beam, which is very advantageous for these kinds of treatments3, 4. The purpose of this work was to find out the difference in the percentage of photo neutron production in a flattening filter free (FFF) and flattening filter (FF) beam using CR39 Solid State Nuclear Track Detector (SSNTD) from an Elekta Versa HD machine. The neutron fluence was measured at different positions with FFF and FF mode and the results were tabulated. The neutron fluence was lower for the FFF mode of operation than the FF mode. The reduction ranges from 2.27% to 44.22%.

Simultaneous Identification of Low and High Atomic Number Atoms in Monolayer 2D Materials Using 4D Scanning Transmission Electron Microscopy

Simultaneous imaging of individual low and high atomic number atoms using annular dark field scanning transmission electron microscopy (ADF-STEM) is often challenging due to substantial differences in their scattering cross sections. This often leads to contrast from only the high atomic number species when imaged using ADF-STEM such as the Mo and 2S sites in monolayer MoS2 crystals, without detection of lighter atoms such as C, O, or N. Here, we show that by capturing an array of convergent beam electron diffraction patterns using a 2D pixelated electron detector (2D-PED) in a 4D STEM geometry enables identification of individual low and high atomic number atoms in 2D materials by multicomponent imaging. We have used ptychographic phase reconstructions, combined with angular dependent ADF-STEM reconstructions, to image light elements at lateral (nanopores) and vertical interfaces (surface dopants) within 2D monolayer MoS2. Differential phase contrast imaging (Div(DPC)) using quadrant segmentation of the 2D pixelated direct electron detector data not only qualitatively matches the ptychographic phase reconstructions in both resolution and contrast but also offers the additional potential for real time display. Using 4D-STEM, we have identified surface adatoms on MoS2 monolayers and have separated atomic columns with similar total atomic number into their relative combinations of low and high atomic number elements. These results demonstrate the rich information present in the data obtained during 4D-STEM imaging of ultrathin 2D materials and the ability of this approach to extract unique insights beyond conventional imaging.

Enhanced cytotoxic and genotoxic effects of gadolinium-doped ZnO nanoparticles on irradiated lung cancer cells at megavoltage radiation energies

The purpose of this study was to investigate the radiation dose enhancement effects of gadolinium-doped zinc oxide nanoparticles (Gd-doped ZnO NPs) under the megavoltage (MV) X-ray irradiation. ZnO NPs have preferred photocatalytic properties under UV light for cancer killing. UV light has limited applications in cancer treatment and it is necessary to use X-ray photons with MV energies. In order to increase the absorption of radiation and also to enhance the imaging visualization capabilities of ZnO NPs, gadolinium (Gd) as a high atomic number element was selected for doping into the structure of ZnO NPs. Gd-doped ZnO NPs were synthesized by a chemical precipitation method and characterized by transmission electron microscopy, powder X-ray diffraction, ultraviolet-visible spectroscopy, and energy-dispersive X-ray techniques. Cellular uptake was assessed by TEM and inductively coupled plasma mass spectrometry. NPs cytotoxicity was analyzed by MTT assay and radiation dose enhancement was measured by clonogenic survival assay. Apoptosis induction, cell cycle progression, micronucleus formation and expression of DNA double-strand break repair genes of XRCC2 and XRCC4 were determined by flow cytometry, micronucleus assay, and quantitative real-time polymerase chain reaction. CT and MR imaging were used to analyze the image visualization capabilities of NPs. NPs characterization showed that highly pure crystalline Gd-doped ZnO NPs with a narrow size distribution and grain size of 9 nm were synthesized. Gd-doped ZnO NPs were distributed in the cells and showed dose-dependent toxicity. Combination of Gd-doped ZnO NPs with 6 MV X-rays induced dose-dependent radiosensitivity with sensitizer enhancement ratios (SER) of 1.47 and 1.61 for 10 and 20 μg/mL NPs concentrations. Cancer cells blocked in G1, apoptosis rates, and micronuclei formation was enhanced and inversely, the DNA repair efficiency was impaired by down regulation of the mRNA levels of XRCC2 and XRCC4 genes. Gd-doped ZnO NPs enhanced the contrasts of CT and MR images of cancer cells. Overall, the results of this study provide detailed biological insights on the dose enhancement of Gd-doped ZnO NPs at MV radiations, which would contribute to the further development of this potent theranostic platform for clinical applications.