BACKGROUND/AIM:Iodine-Hoechst (IH) is a derivative of Hoechst dye that binds minor grooves of DNA. This chemical has been used for cell labeling studies such as nuclear staining; however, its use in radiation therapy has not been explored fully. We investigated enhancement of X-ray sensitivity of cancer cells by IH. MATERIALS AND METHODS:Cell survival was examined over a range of X-ray doses, survival curves were generated, and the enhancement ratio (ER) was calculated. Double-strand DNA breaks were examined by a γH2AX assay. We then investigated whether the radiosensitivity-enhancing effect of IH occurs under low oxygen conditions. Additionally, reactive oxygen species (ROS) production was measured using dichlorodihydrofluorescein diacetate. As a first step to investigate the effect of IH on X-ray inhibition of tumor growth, we employed the chorioallantoic membrane (CAM) assay, a simple, versatile cancer model. RESULTS:IH enhanced X-ray sensitivity of cancer cells, with an ER of 1.29 based on 10% survival values. X-ray-induced DNA double-strand breaks were increased by IH. Upon exposing cells to low oxygen conditions, X-ray sensitivity decreased, consistent with the idea that X-ray sensitivity decreases under low oxygen. Even under this condition, IH enhancement persisted, revealing that the radiosensitivity-enhancing effect was not significantly affected by oxygen. This enhancement does not involve ROS, as X-ray-induced ROS production was unchanged by IH. In the CAM assay, transplantation of cancer cells led to tumor formation within the egg. Intravenous injection of IH resulted in the delivery of IH to the tumor. X-ray irradiation of the tumor inhibited tumor growth, and this was enhanced by IH. CONCLUSION:Our results reveal that IH enhances radiation sensitivity of cancer cells, and this effect is observed even under low oxygen conditions.
Two adamantane-containing macrocycles having halobenzene and tetrazine parts were employed as porous host materials in the crystalline sponge method for the structural elucidation of liquid pharmaceutical compounds. The macrocycles were arranged into molecular networks composed of tubular assemblies having onedimensional pores. Soaking of the porous crystals in methyl salicylate or eugenol afforded the adsorbed crystals in a single-crystal to single-crystal fashion. X-ray analysis revealed that the conformation and packing of the macrocycles in the porous crystals were changed compared with those in the original crystals. Similarly, 4-methylpyrazole (also known as fomepizole) or 3-methylpyrazole were captured within the macrocycle-based organic frameworks, and their molecular structures were confirmed. Remarkably, dimeric structures of the pyrazole derivatives were formed within the macrocycles through hydrogen bonds.
Bent-shaped compounds are attractive building blocks because they self-assemble into unique two- or three-dimensional structures. We used bent-shaped host molecule (1), which is composed of two nitrophenols linked to adamantane. Vapor diffusion of hexane into a tetrahydrofuran solution of 1 afforded inclusion crystals. The host molecules were assembled into tetrameric H-shaped structures as a motif through the quadruple pi-stacking of nitrophenol moieties within a unit cell, in which eight hydroxy groups interacted with eight guests through hydrogen bonds. These assemblies were fabricated to form network structures with channels. In inclusion crystals with 1,4-dioxane, 1 was arranged into layer architectures that were packed into the channel structures. In inclusion crystals with gamma-butyrolactone, 1 was aligned into network structures with channels, where cyclic dimeric structures without cavities were formed. These results demonstrate the crucial role of solvent molecules in the creation of tetrameric and dimeric motifs in the crystalline state.
Co-crystallization of a macrocycle and 1,5-dihydroxynaphthalene afforded co-crystals with solvents, which, when soaked in diethyl ether, formed crystals of the macrocycle through solvent exchange and the release of 1,5-dihydroxynaphthalene.
Water-mediated hydrogen-bonded structures were built from a disubstituted adamantane with dimethoxyphenol moieties, where halobenzenes were accommodated within the cavity of cyclic dimers composed of host compounds and waters.
Aims: This study aimed to evaluate the geometrical accuracy of atlas-based auto-segmentation (ABAS), deformable image registration (DIR), and deep learning auto-segmentation (DLAS) in adaptive radiotherapy (ART) for head-and-neck cancer (HNC). Subjects and Methods: Seventeen patients who underwent replanning for ART were retrospectively studied, and delineated contours on their replanning computed tomography (CT2) images were delineated. For DIR, the planning CT image (CT1) of the evaluated patients was utilized. In contrast, ABAS was performed using an atlas dataset comprising 30 patients who were not part of the evaluated group. DLAS was trained with 143 patients from different patients from the evaluated patients. The ABAS model was improved, and a modified ABAS (mABAS) was created by adding the evaluated patients’ own CT1 to the atlas datasets of ABAS (number of patients of the atlas dataset, 31). The geometrical accuracy of DIR, DLAS, ABAS, and mABAS was evaluated. Results: The Dice similarity coefficient in DIR was the highest, at >0.8 at all organs at risk. The mABAS was delineated slightly more accurately than the standard ABAS. There was no significant difference between ABAS and DLAS in delineation accuracy. DIR had the lowest Hausdorff distance (HD) value (within 10 mm). The HD values in ABAS, mABAS, and DLAS were within 16 mm. Conclusions: DIR delineation is the most geometrically accurate ART for HNC.
The increase in high-precision radiation therapy, particularly volumetric-modulated arc therapy (VMAT), has increased patient numbers and expanded treatment sites. However, a significant challenge in VMAT treatment planning is the inconsistent plan quality among different planners and facilities. This study explored the use of dose-volume histogram (DVH) prediction tools to address these disparities, specifically focusing on RapidPlan (Varian Medical Systems) and PlanIQ (Sun Nuclear). RapidPlan predicts achievable DVHs and automatically generates optimization objectives. While it has demonstrated organ-at-risk (OAR) dose reduction benefits, the quality of the plan used to build its model significantly affects its predictions. On the other hand, PlanIQ offers ease of use and does not require prior model-building. Five planners participated in this study, each creating two treatment plans: one referencing RapidPlan and the other using PlanIQ. The planners had the freedom to adjust parameters while referencing the DVH predictions. The plans were evaluated using “Plan Quality Metric” (PQM) scores to assess the planning target volume excluding the rectum and OARs. The results revealed that RapidPlan-referenced plans often outperformed PlanIQ-based plans, with less interplanner variability. PlanIQ played a pivotal role in the construction of the RapidPlan model. This study is the first to compare plans generated by multiple planners using both tools. This study provides insights into optimizing treatment planning by considering the characteristics of both RapidPlan and PlanIQ.
Ketones and esters were captured within porous crystals of an adamantane-containing macrocycle through single-crystal-to-single-crystal guest exchange with or without structural changes.
This study evaluated the effect of pitch on 256-slice helical computed tomography (CT) scans. Cylindrical water phantoms (CWP) were measured using axial and helical scans with various pitch values. The surface dose distributions of CWP were measured, and reconstructed images were obtained using filtered back-projection (FBP) and iterative model reconstruction (IMR). The image noise in each reconstructed image was decomposed into a baseline component and another component that varied along the z-axis. The baseline component of the image noise was highest at the center of the reconstructed image and decreased toward the edges. The normalized 2D power spectra for each pitch were almost identically distributed. Furthermore, the ratios of the 2D power spectra for IMR and FBP at different pitch values were obtained. The magnitudes of the components varying along the z-axis were smallest at the center of the reconstructed image and increased toward the edge. The ratios of the 3D power spectra on the fx axis for IMR and FBP at different pitch values were obtained. The results showed that the effect of the pitch was related to the component that varied along the z-axis. Furthermore, the pitch had a smaller effect on IMR than on FBP.
Inclusion crystals were formed from ketones with aromatic diimide-based macrocycles possessing adamantane units, where the oxygen atoms of guests interacted with the electron-deficient π-surfaces of the aromatic diimides through CO⋯π contacts.
One ketone or ester guest molecule was captured by multiple disubstituted adamantane units having nitrophenol moieties through multiple intermolecular interactions including OH⋯O and CH⋯O interactions.
Inclusion crystals containing several halocarbons were formed by three types of diimide-based macrocycles. Iodomethane was encapsulated within the cavity of the macrocycle through halogen-related interactions.
Adamantane-based macrocycles with pyrazine or tetrazine units afforded porous crystals with distinct surface properties of 1D pores, which captured multiple water molecules from the air or liquid water in a single-crystal-to-single-crystal fashion.
Two macrocycles having adamantane, aromatic units, and propargyl groups (1, 2) were synthesized and their molecular alignments were investigated for the purpose of creating tubular and pseudopolyrotaxane structures. Macrocycles 1 and 2 have distinct molecular sizes and shapes and possess eight and four substituents, respectively. Each macrocycle afforded two inclusion crystals from two solvent systems. The two crystals of 1 had different macrocyclic backbones and orientation of propargyl groups, and columnar or tubular structures were constructed from 1. In the two crystals of 2, the macrocyclic skeleton and the propargyl groups adopted different geometries. In one crystal of 2, two of the substituents were mutually included within the cavity of the adjacent macrocycles to afford one-dimensional polymers with pseudorotaxane-like structures. In the other crystal of 2, the macrocycles were aligned to form columnar structures. Propargyl groups interacted with other units through mainly CH···π interactions.
Y The crystallization of molecular tweezer (1), which is composed of two 1,8-naphthalimide units and a diphenyladamantane spacer, resulted in the formation of two inclusion crystals (1a, 1b) depending on the crystallization solvent used. X-ray crystallographic analysis of the two crystals revealed that 1 had a U-shaped conformation and its dimerization produced naphthalimide quadruple pi stacks in an antiparallel fashion. The overlapping of the four naphthalimide units in the non-covalently associated dimeric structures of crystal 1a was larger than that of crystal 1b. The dimeric structures were assembled into network architectures through intermolecular interactions. In inclusion crystal (2a) of compound 2 containing 2,3-naphthalimide units, 2 adopted a Z-shaped conformation in contrast to 1, indicating that discrete dimeric structures of quadruple pi stacks were not generated. (C) 2021 Elsevier B.V. All rights reserved.
The evaluation of the entrance surface dose (ESD) ensures safe radiation doses for X-ray imaging patients. The air kerma free-in-air value used to estimate ESD may be affected by those X-rays that scatter from the scatterer placed behind the chamber at the time of measurement, thereby leading to assessment errors. Therefore, the influence of scattered radiation on air kerma measurements was investigated. Monte Carlo simulations were performed for various detector-to-scatterer distances and scatterer materials. The simulation results were compared with actual measurements to confirm the simulation accuracy. The source–chamber distance was set to 50 and 100 cm for the experimental measurements and simulation, respectively, and the chamber–scatterer distance was varied. The Monte Carlo simulation results reproduced the actual measurements with an accuracy of 3.5%. The effect of backscattering varied with the tube voltage and irradiation field size. The effect was observed in the order of prominence for the following scatterer materials: water-equivalent phantom, acrylic, concrete, lead, and iron. Furthermore, this effect decreased exponentially with increasing chamber–scatterer distance. For a field size of 10 × 10 cm2, the finite-distance backscatter factor decreased with an increasing chamber–scatterer distance for all materials. The cause of backscattering in diagnostic X-ray energy regions differs depending on the scatterer material, as well as the photon energy and field size. Backscattering decreases exponentially as the distance between the detector and scatterer increases.
An adamantane-bearing macrocycle exhibited permanent intrinsic porosity and adsorption of small guests in single-crystal-to-single-crystal fashions. The guest capture resulted in the structural transformations of supramolecular organic frameworks.
An adamantane-based macrocycle afforded three inclusion crystals with diverse 1D channels. Single-crystal to single-crystal guest exchanges occurred for two crystals, where their frameworks displayed distinctive structural transformations.
Purpose A recent report by the American Association of Physicists in Medicine Task Group 75 and 180 provided imaging dose estimates for image-guided CyberKnife radiotherapy. However, to our knowledge, there have been no concrete demonstrations of imaging intervals that are directly linked to exposure dose. We hypothesized that setting a rational standard may be clearer through a balance of treatment accuracy and reducing imaging doses if the margin of the planned treatment volume is controlled through the imaging interval. This study was conducted to simulate the association between the imaging interval and intrafraction displacement and to estimate a reasonable internal margin (IM). Methods We retrospectively analyzed data from 21 shell-fixed heads of patients treated with CyberKnife G3 using our dedicated monitoring system. This system comprises pressure sensors that can monitor head displacement every 0.2 s in the absence of any imaging dose. First, the root sum square of head displacements was calculated in 76 treatment fractions with an imaging interval of 10-1440 s. The cumulative frequency of a root sum square displacement (which was less than the IM) was evaluated in image verifications that were undertaken 546 274 times for every imaging interval. Results We found that the mean values and SDs of the displacement were larger in proportion to the imaging interval (p < 0.002) and that the maximum displacements did not correlate in any combination within 720 s (p > 0.056). The cumulative frequencies of displacement of 0.6 and 1.4 mm (i.e., less than an IM) were 99.2% and 99.1% for imaging intervals of 10 and 360 s, respectively. Conclusions In the current study, we found that imaging intervals were directly proportional to intrafraction displacement and that there was no correlation in any combination within 720 s. Imaging intervals for an IM of 0.6 and 1.4 mm were 10 and 360 s, respectively, with a 99% confidence interval of intrafraction displacement. With CyberKnife M6 or a previous version of this system, the imaging dose could be reduced by 0.4760 mSv per 24-min treatment as the imaging dose ranged from 0.4896 to 0.0136 mSv for imaging intervals of 10 and 360 s with an IM of 0.6 and 1.4 mm, respectively. A rational method that includes X-ray imaging guidance may be achieved with modulation of the imaging interval via the CyberKnife system.
AbstractVolumetric‐modulated arc therapy (VMAT) requires highly accurate control of multileaf collimator (MLC) movement, rotation speed of linear accelerator gantry, and monitor units during irradiation. Pretreatment validation and monitoring of these factors during irradiation are necessary for appropriate VMAT treatment. Recently, a gantry mounted transmission detector “Delta4 Discover® (D4D)” was developed to detect errors in delivering doses and dose distribution immediately after treatment. In this study, the performance of D4D was evaluated. Simulation plans, in which the MLC position was displaced by 0.5, 1.0, 1.5, 2.0, 2.5, and 3.0 mm from the clinically used original plans, were created for ten patients who received VMAT treatment for prostate cancer. Dose deviation (DD), distance‐to‐agreement (DTA), and gamma index analysis (GA) for each plan were evaluated by D4D. These results were compared to the results (DD, DTA and GA) measured by Delta4 Phantom + (D4P). We compared the deviations between the planned and measured values of the MLC stop positions A‐side and B‐side in five clinical cases of prostate VMAT during treatment and measured the GA values. For D4D, when the acceptable errors for DD, DTA, and GA were determined to be ≤3%, ≤2 mm, and ≤3%/2 mm, respectively, the minimum detectable errors in the MLC position were 2.0, 1.5, and 1.5 mm based on DD, DTA, and GA respectively. The corresponding minimum detectable MLC position errors were 2.0, 1.0, and 1.5 mm, respectively, for D4P. The deviation between the planned and measured position of MLC stopping point of prostate VMAT during treatment was stable at an average of −0.09 ± 0.05 mm, and all GA values were above 99.86%. In terms of delivering doses and dose distribution of VMAT, error detectability of D4D was comparable to that of D4P. The transmission‐type detector “D4D” is thus suitable for detecting delivery errors during irradiation.