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17 pages, 6877 KB  
Systematic Review
Diagnostic Efficacy of FAPI-PET/CT Versus [18F]FDG-PET/CT in Upper-Abdominal Malignancies: A Systematic Review and Meta-Analysis
by Hao Huang, Betül Altunay, Laura Schäfer, Christian Boy, Dirk von Mallek, Felix M. Mottaghy and Susanne Lütje
Diagnostics 2026, 16(4), 520; https://doi.org/10.3390/diagnostics16040520 - 9 Feb 2026
Viewed by 187
Abstract
Background: Radiolabeled fibroblast activation protein inhibitors (FAPIs) have emerged as novel radiopharmaceutical agents for tumor diagnosis. Compared with [18F]fluoro-2-deoxy-D-glucose ([18F]FDG), which reflects glucose uptake in metabolically active regions, FAPIs mainly bind to the fibroblast activation protein (FAP), which [...] Read more.
Background: Radiolabeled fibroblast activation protein inhibitors (FAPIs) have emerged as novel radiopharmaceutical agents for tumor diagnosis. Compared with [18F]fluoro-2-deoxy-D-glucose ([18F]FDG), which reflects glucose uptake in metabolically active regions, FAPIs mainly bind to the fibroblast activation protein (FAP), which is highly expressed in tumor-associated fibroblasts, forming a pronounced signal. Several studies suggested potential superiority of FAPI tracers above [18F]FDG-based imaging in a variety of tumor entities. In this systematic review, we focus on the comparison of FAPI-PET/CT and [18F]FDG-PET/CT in upper-abdominal tumors. Methods: Original research published from 1 January 2021 to 22 December 2024 was collected from the PubMed and Web of Science databases (CRD42025648267). This research included only clinical studies, excluding conference abstracts and case reports. The risk of bias was assessed with the QUADAS-2 tool, and all evaluation steps performed independently by three independent reviewers. A systematic quality assessment of the included studies was conducted based on the imaging performance of FAPI-PET/CT and [18F]FDG-PET/CT for pancreatic, liver, and gastric cancers. The meta-analysis used relative risk (RR) as the effect size, with bias assessed via the Peters test (p-value > 0.05). Cochran’s Q test and I-squared value are used to comprehensively evaluate the magnitude of heterogeneity. Analyses and data visualization were performed in R language. Results: The database search identified 3272 articles. After screening, 31 studies were included in this analysis. The original studies enrolled 1377 participants (M/F: 850/527; ages predominantly between 50 and 70). Of these, 939 patients were ultimately diagnosed with tumors (five cancer subtypes) and included in this analysis. Meta-analysis results showed that FAPI-PET/CT significantly surpassed [18F]FDG-PET/CT in the detection of primary lesions (RRs = 1.20 and 1.17), lymph nodes (RRs = 1.18 and 1.24), distant metastases (RRs = 1.22 and 1.51), peritoneal metastases (RRs = 1.31 and 2.22), and bone metastases (RRs = 1.16 and 1.23). The two imaging methods exhibit clear differences in diagnostic performance (sensitivity: 98% vs. 79%; specificity: 83% vs. 87%), and FAPI-PET/CT demonstrates high and stable diagnostic performance (RRs = 1.20 and 1.17). Conclusions: Compared with [18F]FDG-PET/CT, FAPI-PET/CT demonstrates significant advantages in detecting primary lesions, lymph nodes, distant metastases, and peritoneal and bone metastases in pancreatic, liver, and gastric cancers (RR > 1.0). Overall, FAPI-PET/CT shows better diagnostic performance (RR > 1.0). Full article
(This article belongs to the Section Medical Imaging and Theranostics)
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24 pages, 577 KB  
Article
Quality-by-Design Compounding of Semisolids Using an Electronic Mortar and Pestle Device for Compounding Pharmacies: Uniformity, Stability, and Cleaning
by Hudson Polonini, Carolina Schettino Kegele, Savvas Koulouridas and Marcone Augusto Leal de Oliveira
Pharmaceutics 2026, 18(2), 205; https://doi.org/10.3390/pharmaceutics18020205 - 4 Feb 2026
Viewed by 462
Abstract
Background/Objectives: Manual preparation of semisolid formulations (creams, ointments, gels) is prone to variability in mixing energy and time, which may compromise uniform API distribution. This study aimed to evaluate an Electronic Mortar and Pestle (EMP; Unguator™) as a standardized compounding tool, with [...] Read more.
Background/Objectives: Manual preparation of semisolid formulations (creams, ointments, gels) is prone to variability in mixing energy and time, which may compromise uniform API distribution. This study aimed to evaluate an Electronic Mortar and Pestle (EMP; Unguator™) as a standardized compounding tool, with objectives to: (i) validate stability-indicating UHPLC methods; (ii) assess content uniformity across jar strata; (iii) quantify the impact of mixing time and rotation speed via design of experiments (DOE); and (iv) verify cleaning effectiveness and cross-contamination risk. Methods: Five representative formulations were compounded: urea 40%, clobetasol 0.05%, diclofenac 2.5% in hyaluronic acid 3% gel, urea 10% + salicylic acid 1%, and hydroquinone 5%. UHPLC methods were validated per ICH Q2(R2) and stress-tested under acid, base, oxidative, thermal, and UV conditions. Homogeneity was assessed by stratified sampling (top/middle/bottom). A 32 factorial DOE (time: 2/6/10 min; speed: 600/1500/2400 rpm) modeled effects on % label claim and RSD. Cleaning validation employed hydroquinone as a tracer, with swab sampling pre-/post-use and post-sanitization analyzed by HPLC. Results: All UHPLC methods met specificity, linearity, precision, accuracy, and sensitivity criteria and were stability-indicating (Rs ≥ 1.5). Formulations achieved 90–110% label claim with strata CV ≤ 5%. DOE revealed speed as the dominant factor for clobetasol, urea, and diclofenac, while time was more influential for salicylic acid; gels exhibited curvature, indicating diminishing returns at high rpm. Model-predicted optima were implementable on the Unguator™ with minor rounding of rpm/time. Cleaning validation confirmed post-sanitization residues below LOQ and <10 ppm acceptance. Conclusions: The Unguator™ provides a practical, parameter-controlled route for compounding pharmacies to standardize semisolid preparations, achieving reproducible layer-to-layer content uniformity within predefined criteria under the evaluated conditions through programmable set-points and validated cycles. DOE-derived rpm–time relationships define an operational design space within the studied ranges and support selection of implementable device settings and set-points. Importantly, the DOE-derived “optima” in this study are optimized for assay-based content uniformity (mean % label claim and strata variability). Cleaning validation supports a closed, low-cross-contamination workflow, facilitating consistent routines for both routine and complex formulations. Overall, the work implements selected QbD elements (QTPP—Quality Target Product Profile; CQA—Critical Quality Attribute definition; CPP—Critical Process Parameter identification; operational design space; and a proposed control strategy) and should be viewed as a step toward broader lifecycle QbD implementation in compounding. Full article
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21 pages, 2527 KB  
Article
Relative Evaluation Approach for Cross-Room Exposure in a Detached House Using a Measurement-Informed Multizone Model
by Akihiro Katsuki, Koki Kikuta, Yu Tanaka, Masato Iguchi and Motoya Hayashi
Buildings 2026, 16(3), 583; https://doi.org/10.3390/buildings16030583 - 30 Jan 2026
Viewed by 226
Abstract
Household airborne transmission can be promoted when infectious and susceptible occupants share indoor air for long periods, yet practical infection-risk models often require pathogen-specific parameters that are uncertain. This study proposes a measurement-informed multizone/HVAC-network workflow that identifies inter-room airflow rates (q) [...] Read more.
Household airborne transmission can be promoted when infectious and susceptible occupants share indoor air for long periods, yet practical infection-risk models often require pathogen-specific parameters that are uncertain. This study proposes a measurement-informed multizone/HVAC-network workflow that identifies inter-room airflow rates (q) from CO2 tracer time series and estimates an effective first-order non-ventilation aerosol loss rate (λ) by fitting PM2.5 concentration decay dynamics; the identified parameters are then reused within the same whole-house recirculating network model (vtsim) to compute a steady-state exhaled-air tracer concentration index for scenario comparison. The workflow is demonstrated in a high-insulation, airtight detached house equipped with a duct-type whole-house air-conditioning system with return-air recirculation. The results indicate measurable cross-room dispersion under baseline operation and show that a return-side filtration scenario reduces the steady-state index in non-source rooms relative to baseline under the tested operating assumptions. These findings illustrate how measurement-informed identification can support rapid, threshold-free relative comparison of ventilation/HVAC operation or mitigation scenarios within a specific house, rather than estimating absolute infection probability. Limitations include potential non-uniqueness in inverse identification, simplified treatment of leakage and pressure-drop-induced airflow changes, and the use of a steady-state index for inherently transient residential exposures; further validation across additional houses and HVAC topologies is warranted. Full article
(This article belongs to the Section Building Energy, Physics, Environment, and Systems)
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16 pages, 6944 KB  
Article
Water Shutoff with Polymer Gels in a High-Temperature Gas Reservoir in China: A Success Story
by Tao Song, Hongjun Wu, Pingde Liu, Junyi Wu, Chunlei Wang, Hualing Zhang, Song Zhang, Mantian Li, Junlei Wang, Bin Ding, Weidong Liu, Jianyun Peng, Yingting Zhu and Falin Wei
Energies 2025, 18(24), 6554; https://doi.org/10.3390/en18246554 - 15 Dec 2025
Viewed by 452
Abstract
Gel treatments have been widely applied to control water production in oil and gas reservoirs. However, for water shutoff in dense gas reservoirs, most gel-based treatments focus on individual wells rather than the entire reservoir, exhibiting limited treatment depth, poor durability, and inadequate [...] Read more.
Gel treatments have been widely applied to control water production in oil and gas reservoirs. However, for water shutoff in dense gas reservoirs, most gel-based treatments focus on individual wells rather than the entire reservoir, exhibiting limited treatment depth, poor durability, and inadequate repeatability Notably, formation damage is a primary consideration in treatment design—most dense gas reservoirs have a permeability of less than 1 mD, making them highly susceptible to damage by formation water, let alone viscous polymer gels. Constrained by well completion methods, gelant can only be bullheaded into deep gas wells in most scenarios. Due to the poor gas/water selective plugging capability of conventional gels, the injected gelant tends to enter both gas and water zones, simultaneously plugging fluid flow in both. Although several techniques have been developed to re-establish gas flow paths post-treatment, treating gas-producing zones remains risky when no effective barrier exists between water and gas strata. Additionally, most water/gas selective plugging materials lack sufficient thermal stability under high-temperature and high-salinity (HTHS) gas reservoir conditions, and their injectivity and field feasibility still require further optimization. To address these challenges, treatment design should be optimized using non-selective gel materials, shifting the focus from directly preventing formation water invasion into individual wells to mitigating or slowing water invasion across the entire gas reservoir. This approach can be achieved by placing large-volume gels along major water flow paths via fully watered-out wells located at structurally lower positions. Furthermore, the drainage capacity of these wells can be preserved by displacing the gel slug to the far-wellbore region, thereby dissipating water-driven energy. This study evaluates the viability of placing gels in fully watered-out wells at structurally lower positions in an edge-water drive gas reservoir to slow water invasion into structurally higher production wells interconnected via numerous microfractures and high-permeability streaks. The gel system primarily comprises polyethyleneimine (PEI), a terpolymer, and nanofibers. Key properties of the gel system are as follows: Static gelation time: 6 h; Elastic modulus of fully crosslinked gel: 8.6 Pa; Thermal stability: Stable in formation water at 130 °C for over 3 months; Injectivity: Easily placed in a 219 mD rock matrix with an injection pressure gradient of 0.8 MPa/m at an injection rate of 1 mL/min; and Plugging performance: Excellent sealing effect on microfractures, with a water breakthrough pressure gradient of 2.25 MPa/m in 0.1 mm fractures. During field implementation, cyclic gelant injections combined with over-displacement techniques were employed to push the gel slug deep into the reservoir while maintaining well drainage capacity. The total volumes of injected fluid and gelant were 2865 m3 and 1400 m3, respectively. Production data and tracer test results from adjacent wells confirmed that the water invasion rate was successfully reduced from 59 m/d to 35 m/d. The pilot test results validate that placing gels in fully watered-out wells at structurally lower positions is a viable strategy to protect the production of gas wells at structurally higher positions. Full article
(This article belongs to the Special Issue New Advances in Oil, Gas and Geothermal Reservoirs—3rd Edition)
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14 pages, 1574 KB  
Article
Accurate Construction of a Transient Groundwater Flow Model for a Near-Surface Disposal Site
by Weizhe Cui, Jie Wang, Haifeng Liu, Yuchen Wang, Jingli Shao and Qiulan Zhang
Appl. Sci. 2025, 15(24), 12905; https://doi.org/10.3390/app152412905 - 7 Dec 2025
Viewed by 363
Abstract
Numerical simulation of groundwater level dynamics plays a crucial role in the safety assessment of near-surface radioactive waste disposal facilities. Such disposal sites are typically located in regions characterized by extensive bedrock outcrops. However, accurately characterizing the permeability of fractured media is challenging, [...] Read more.
Numerical simulation of groundwater level dynamics plays a crucial role in the safety assessment of near-surface radioactive waste disposal facilities. Such disposal sites are typically located in regions characterized by extensive bedrock outcrops. However, accurately characterizing the permeability of fractured media is challenging, and the scarcity of groundwater level data poses significant difficulties for constructing reliable numerical models. This study focuses on a near-surface disposal site in northwestern China. By integrating field packer tests with hydraulic conductivity tensors computed from borehole televiewer data, we quantitatively evaluated the permeability of fractured rocks of different lithologies to provide accurate parameters for numerical modeling. The constructed groundwater flow model was further calibrated and validated using long-term groundwater level monitoring data and field tracer-based groundwater flow direction tests, ensuring high model reliability. Using the calibrated model, groundwater level variations were simulated under various rainfall and pumping scenarios. The results show that pumping intensity in the downstream farmland area exerts a limited influence on groundwater levels beneath the disposal site, while rainfall intensity plays a dominant role. Under the heavy rainfall scenario, the groundwater level at the disposal site rises by approximately 5.2 m after 50 years, leaving a 6 m gap above the base of the disposal unit. Under prolonged heavy rainfall conditions, implementing drainage measures may be necessary to ensure the repository’s long-term safety. Full article
(This article belongs to the Special Issue Hydrogeology and Regional Groundwater Flow)
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12 pages, 2651 KB  
Article
Identification and Evaluation of Fracturing Advantageous Lithofacies in the Main Structural Zone of Yingxiongling, Qaidam Basin
by Yuan Yao, Yinghao Shen, Menglin Zhang and Muyang Zhang
Processes 2025, 13(12), 3857; https://doi.org/10.3390/pr13123857 - 29 Nov 2025
Viewed by 396
Abstract
The Yingxiongling structural zone in the Qaidam Basin is a critical yet challenging target for shale oil exploration due to strong reservoir heterogeneity and complex sedimentary cycles. This study employs an integrated methodology combining laboratory rock mechanical tests, field fracturing diagnostics, and tracer [...] Read more.
The Yingxiongling structural zone in the Qaidam Basin is a critical yet challenging target for shale oil exploration due to strong reservoir heterogeneity and complex sedimentary cycles. This study employs an integrated methodology combining laboratory rock mechanical tests, field fracturing diagnostics, and tracer data to evaluate the fracturing performance of dominant lithofacies. Results indicate that: (1) Laminated dolomitic limestone exhibits higher mechanical strength and requires elevated fracturing pressure compared to laminated shale, but contains inferior hydrocarbon content. In contrast, laminated shale develops more uniform and complex fracture networks post-fracturing. (2) A lower microseismic b-value in laminated dolomitic limestone suggests shear-dominated failure along bedding planes, enhancing micro-fracture development. (3) Pressure decline analysis and microseismic monitoring confirm that laminated shale facilitates higher fracture network complexity. In conclusion, laminated shale is identified as the preferred lithofacies in the Yingxiongling area, as it possesses a superior potential for generating complex fracture networks that meet the technical requirements for effective volume stimulation. Full article
(This article belongs to the Special Issue Advances in Combustion Processes: Fundamentals and Applications)
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20 pages, 8447 KB  
Article
Delineation Using Multi-Tracer Tests and Hydrochemical Investigation of the Matica River Catchment at Plitvice Lakes, Croatia
by Tihomir Frangen, Ivana Boljat, Hrvoje Meaški and Josip Terzić
Water 2025, 17(22), 3261; https://doi.org/10.3390/w17223261 - 14 Nov 2025
Viewed by 609
Abstract
In the Plitvice Lakes National Park, several hydrogeological catchments can be distinguished, but their boundaries are not clearly defined. This study focused on the Matica River catchment area, which covers the main contributors to the lake system and its overall water balance. An [...] Read more.
In the Plitvice Lakes National Park, several hydrogeological catchments can be distinguished, but their boundaries are not clearly defined. This study focused on the Matica River catchment area, which covers the main contributors to the lake system and its overall water balance. An initial assessment indicated that the Matica River catchment is among the most vulnerable areas due to the anticipated land-use expansion related to agriculture and tourism. This research provides critical hydrogeological data supporting sustainable management in response to the increasing extremes of floods and droughts induced by climate change. Two separate campaigns (March 2023 and April 2025) were carried out, each involving three simultaneous tracer injections using different fluorescent dyes. The results of earlier tracer tests were evaluated; furthermore, a hydrochemical analysis of the spring water offered valuable insights into subsurface processes and anthropogenic impacts. Tracing in the southwest clarified the boundary between the Plitvice Lakes and Una River catchments. In the Homoljac polje, the tracer responses highlighted a triple junction between the Plitvice Lakes, Gacka, and Una River catchments. In the southeastern Brezovac polje, the boundary between the Crna Rijeka and Bijela Rijeka catchments was delineated in detail. Full article
(This article belongs to the Special Issue Water Management and Geohazard Mitigation in a Changing Climate)
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22 pages, 10322 KB  
Article
Biochars Derived from Diverse Local Tunisian Feedstocks for Environmental Remediation: Physicochemical Properties and Adsorption Behaviour
by Asma Hmaied, Aïda Ben Hassen Trabelsi, Fethi Lachaal, Sandrine Negro and Claude Hammecker
Land 2025, 14(11), 2224; https://doi.org/10.3390/land14112224 - 10 Nov 2025
Viewed by 859
Abstract
Water resource management and agricultural practices in the Mediterranean region, characterised by the excessive use of pesticides, pose significant environmental and human health challenges. As they can be easily and inexpensively produced from various biomass sources, biochars are frequently recommended as a low-cost [...] Read more.
Water resource management and agricultural practices in the Mediterranean region, characterised by the excessive use of pesticides, pose significant environmental and human health challenges. As they can be easily and inexpensively produced from various biomass sources, biochars are frequently recommended as a low-cost secondary decontamination strategy to address soil contamination problems. This study investigates the properties and sorption behaviours of biochars produced in a low-cost metallic kiln using local rosemary, giant reed, St. John’s wort, olive, cypress, and palm tree biomass residues to evaluate their potential for environmental remediation, with a special focus on the mobility and retention of contaminants. Analytical and experimental techniques were employed to characterise the biochars’ physicochemical attributes and sorptive capacities. The core analyses included measurement of basic physicochemical properties, including pH, electrical conductivity, functional group identification via Fourier transform infrared (FTIR) spectroscopy, and the molarity of ethanol droplet (MED) test to assess the surface hydrophobicity. Batch sorption experiments were conducted using methylene blue (MB) and two fluorescent tracers—uranine (UR) and sulforhodamine-B (SRB)—as proxies for organic contaminants to assess the adsorption efficiency and molecule–biochar interactions. Furthermore, the adsorption isotherms at 20 °C were fitted to different models to assess the biochars’ specific surface areas. Thermodynamic parameters were also evaluated to understand the nature and strength of the adsorption processes. The results highlight the influence of feedstock type on the resulting biochar’s properties, thus significantly affecting the mechanism of adsorption. Rosemary biochar was found to have the highest specific surface area (SSA) and cation exchange capacity (CEC), allowing it to adsorb a wide range of organic molecules. Giant reed and palm tree biochars showed similar properties. In contrast, wood-derived biochars generally showed very low SSA, moderate CEC, and low hydrophobicity. The contrasting properties of the three dyes—MB (cationic), UR (anionic), and SRB (zwitterionic)—enabled us to highlight the distinct interaction mechanisms between each dye and the surface functional groups of the different biochars. The reactivity and sorption efficiency of a biochar depend strongly on both the nature of the target molecule and the intrinsic properties of the biochar, particularly its pH. The findings of this study demonstrate the importance of matching biochar characteristics to specific contaminant types for optimised environmental applications, providing implications for the use of tailored biochars in pollutant mitigation strategies. Full article
(This article belongs to the Section Land, Soil and Water)
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27 pages, 10026 KB  
Article
Dynamical Friction Constraints on the Dark Matter Hypothesis Across Astronomical Scales
by Xavier Hernandez and Pavel Kroupa
Universe 2025, 11(11), 367; https://doi.org/10.3390/universe11110367 - 6 Nov 2025
Cited by 2 | Viewed by 1758
Abstract
Dynamical friction implies a consistency check on any system where dark matter particles are hypothesised to explain orbital dynamics requiring more mass under Newtonian gravity than is directly detectable. Introducing the assumption of a dominant dark matter halo will also imply a decay [...] Read more.
Dynamical friction implies a consistency check on any system where dark matter particles are hypothesised to explain orbital dynamics requiring more mass under Newtonian gravity than is directly detectable. Introducing the assumption of a dominant dark matter halo will also imply a decay timescale for the orbits in question. A self-consistency constraint hence arises, such that the resulting orbital decay timescales must be longer than the lifetimes of the systems in question. While such constraints are often trivially passed, the combined dependencies of dynamical friction timescales on the mass and orbital radius of the orbital tracer and on the density and velocity dispersion of the assumed dark matter particles leads to the existence of a number of astronomical systems where such a consistency test is failed. Here, we review cases from stars in ultrafaint dwarf galaxies, galactic bars, satellite galaxies, and, particularly, the multi-period mutual orbits of the Magellanic Clouds, as recently inferred from the star formation histories of these two galaxies, as well as the nearby M81 group of galaxies, where introducing enough dark matter to explain observed kinematics leads to dynamical friction orbital decay timescales shorter than the lifetimes of the systems in question. Taken together, these observations exclude dark matter halos made of particles as plausible explanations for the observed kinematics of these systems. Full article
(This article belongs to the Section Galaxies and Clusters)
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18 pages, 2508 KB  
Article
Predicting Remaining Survival of Glioblastoma Patients with Radiomics Analysis Based on 18F-DOPA PET Images
by Jing Qian, Deanna Hasenauer, William G. Breen, Paul D. Brown, Christopher H. Hunt, Mark S. Jacobson, Derek R. Johnson, Timothy J. Kaufmann, Bradley J. Kemp, Sani H. Kizilbash, Val J. Lowe, Michael W. Ruff, Jann N. Sarkaria, Joon H. Uhm, Mark J. Zakhary, Maasa H. Seaberg, Hok Seum Wan Chan Tseung, Elizabeth S. Yan, Yan Zhang, Nadia N. Laack and Debra H. Brinkmannadd Show full author list remove Hide full author list
Cancers 2025, 17(21), 3560; https://doi.org/10.3390/cancers17213560 - 3 Nov 2025
Cited by 1 | Viewed by 1117
Abstract
Background: Post-treatment prognosis and monitoring are critical for determining the timing of salvage treatment in glioblastoma patients but has been challenging due to difficulties differentiating progression from treatment effects in conventional images. This exploratory study aimed to establish the correlation of radiomics image [...] Read more.
Background: Post-treatment prognosis and monitoring are critical for determining the timing of salvage treatment in glioblastoma patients but has been challenging due to difficulties differentiating progression from treatment effects in conventional images. This exploratory study aimed to establish the correlation of radiomics image features from time series of amino acid tracer 18F-DOPA PET images, with outcomes, using machine learning and dimension reduction analysis. Methods: 18F-DOPA PET images were collected for a patient cohort with wild-type IDH and unmethylated MGMT who underwent dose-escalated radiation therapy. Quantitative features were derived from the high uptake region (T/N > 2.0) in pre- and post-radiation therapy follow-up 18F-DOPA PET images. A customized workflow was utilized for pre-selecting predictive features, followed by manifold learning. Machine learning algorithms were employed to establish associations between imaging features and remaining survival (RS), defined as the time between a follow-up scan and date of death. Results: The ML models exhibited 81–83% ROC_AUC in predicting RS evaluated on an independent test dataset. A RS map is proposed for monitoring tumor alterations through serial 18F-DOPA PET scans, demonstrating superior sensitivity and better correlation with survival compared to the RANO criteria. Conclusions: Our study demonstrates that ML models utilizing FU 18F-DOPA PET images have the potential to effectively predict future survival outcomes in patients with glioblastoma treated with dose-escalated radiation therapy. The capability to assess changes in tumor over time through imaging can potentially assist in patient stratification and the selection of salvage treatments, while also aiding in distinguishing treatment effects from genuine tumor progression. Full article
(This article belongs to the Special Issue Radiomics and Imaging in Cancer Analysis)
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22 pages, 3140 KB  
Article
Comparative Preclinical Evaluation of the Tumor-Targeting Properties of Radioiodine and Technetium-Labeled Designed Ankyrin Repeat Proteins for Imaging of Epidermal Growth Factor Receptor Expression in Malignant Tumors
by Mariia Larkina, Gleb Yanovich, Lutfi Aditya Hasnowo, Ruslan Varvashenya, Feruza Yuldasheva, Maria Tretyakova, Evgenii Plotnikov, Roman Zelchan, Alexey Schulga, Elena Konovalova, Rustam Ziganshin, Mikhail V. Belousov, Vladimir Tolmachev and Sergey M. Deyev
Int. J. Mol. Sci. 2025, 26(21), 10609; https://doi.org/10.3390/ijms262110609 - 31 Oct 2025
Cited by 1 | Viewed by 729
Abstract
Radionuclide molecular imaging of epidermal growth factor receptor (EGFR) expression might permit the selection of patients for EGFR-targeting therapies. Designed ankyrin repeat protein (DARPin) E01 with a high affinity to the ectodomain III of the EGFR is a possible EGFR imaging probe. The [...] Read more.
Radionuclide molecular imaging of epidermal growth factor receptor (EGFR) expression might permit the selection of patients for EGFR-targeting therapies. Designed ankyrin repeat protein (DARPin) E01 with a high affinity to the ectodomain III of the EGFR is a possible EGFR imaging probe. The goal of this study was to evaluate the potential of radiolabeled DARPin E01 for in vivo imaging of EGFR. DARPin E01 containing the (HE)3-tag was site-specifically labeled with a residualizing 99mTc (using 99mTc]Tc(CO)3). Two methods providing non-residualizing 123I labels, direct electrophilic radioiodination and indirect radioiodination using [123I]I-para-iodobenzoate (PIB), were tested. [99mTc]Tc-(HE)3-E01 and [123I]I-(HE)3-E01-PIB preserved specific binding to EGFR-expressing cells and affinity in the single-digit nanomolar range. Direct labeling with 123I resulted in a substantial loss of binding. In vitro cellular processing studies showed that both [99mTc]Tc-(HE)3-E01 and [123I]I-(HE)3-E01-PIB had rapid binding and relatively slow internalization. Evaluation of [99mTc]Tc-(HE)3-E01 biodistribution in normal CD1 mice showed that its hepatic uptake was non-saturable, suggesting that this tracer does not bind to murine EGFR. A side-by-side comparison of biodistribution and tumor targeting of [99mTc]Tc-(HE)3-E01 and [123I]I-(HE)3-E01-PIB was performed in Nu/j mice bearing EGFR-positive A-431 and EGFR-negative Ramos human cancer xenografts. Both radiolabeled DARPins demonstrated EGFR-specific tumor uptake. However, [123I]I-(HE)3-E01-PIB had appreciably lower uptake in normal organs compared to [99mTc]Tc-(HE)3-E01, which provided significantly (p < 0.05) higher tumor-to-organ ratios. Gamma-camera imaging confirmed that [123I]I-(HE)3-E01-PIB demonstrated a higher imaging contrast in preclinical models than [99mTc]Tc-(HE)3-E01. In conclusion, DARPin (HE)3-E01 labeled using a non-residualizing [123I]I-para-iodobenzoate (PIB) label is the preferred radiotracer for in vivo imaging of EGFR expression in cancer. Full article
(This article belongs to the Section Biochemistry)
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16 pages, 3190 KB  
Article
Design, Synthesis and Evaluation of the First 2-Alkynyl(aza)indole 18F Probe Targeting α-Synuclein Aggregates
by Liliana Boiaryna, Laura Pieri, Sylvie Chalon, Sophie Serrière, Sylvie Bodard, Gabrielle Chicheri, Elisa Chenaf, Franck Suzenet, Ronald Melki, Frédéric Buron, Sylvain Routier and Johnny Vercouillie
Pharmaceuticals 2025, 18(11), 1638; https://doi.org/10.3390/ph18111638 - 29 Oct 2025
Viewed by 748
Abstract
Background/Objectives: The role of α-synuclein (α-syn) in the pathogenesis of Parkinson’s disease (PD) or neurodegenerative diseases such as Lewy body dementia (LBD) and multiple system atrophy (MSA) is commonly accepted. Through different physiological dysfunctions, abnormal forms of α-syn are generated. These abnormal [...] Read more.
Background/Objectives: The role of α-synuclein (α-syn) in the pathogenesis of Parkinson’s disease (PD) or neurodegenerative diseases such as Lewy body dementia (LBD) and multiple system atrophy (MSA) is commonly accepted. Through different physiological dysfunctions, abnormal forms of α-syn are generated. These abnormal aggregates accumulate and alter pre- and postsynaptic transmission, in particular that of dopamine. Thus, the development of a diagnostic biomarker of synucleinopathies remains crucial and challenging. The development of an α-syn positron emission tomography (PET) radiopharmaceutical may be suitable to early diagnose and stratify patients, follow up disease progression, and evaluate future therapies. Methods: To develop a selective α-syn PET tracer, we synthesized an original series based on alkynyl(aza)indoles. Fifteen final ligands were synthesized bearing indoles or azaindoles from one side of the alkyne and a substituted phenyl ring for the opposite side of the alkyne. The final ligands were tested to determine Ki and/or Kd toward α-syn, tau, and Aβ. Results: The SAR showed that the indole series exhibited moderate to low affinity for α-syn and, moreover, lower Ki toward Aβ and tau (i.e., compound 39, Ki(αsyn) 21.7 nM, Ki(Aβ) 64.4 nM, Ki(Tau) 27.6 nM), highlighting the low potency of these series to afford an α-syn tracer. The introduction of a nitrogen on the different positions of the phenyl to obtain the corresponding azaindoles resulted for most of the compounds in better affinity for α-syn and selectivity towards Aβ compared to the indole analogs (i.e., compound 43, Ki(αsyn) 4.7 nM, Ki(Aβ) 24.4 nM, and Ki(Tau) 4.61 nM). A fluorinated azaindole derivative was prepared with a view to obtaining a 18F tracer and exhibited the highest affinity for α-syn but without selectivity against tau and Aβ. The radiosynthesis of [18F]45 was performed in a two-step procedure starting from the tosylated and protected precursor. [18F]45 was obtained in 85 ± 5 min with a radiochemical yield of 32 ± 3%. Molar activity, determined from a calibration with stable 45, was around 130 GBq/µmole. The dynamic PET imaging showed that [18F]45 was able to cross the blood–brain barrier, but non-specific uptake was observed, confirming the in vitro results. Conclusions: Although promising nanomolar affinity for the target, the new tracer showed mainly non-specific in vivo uptake in the rat brain, indicating that further pharmacomodulations on the azaindole series are required. Full article
(This article belongs to the Section Radiopharmaceutical Sciences)
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13 pages, 4332 KB  
Article
Brain Perfusion Scintigraphy in the Diagnostic Toolbox for the Confirmation of Brain Death: Practical Aspects and Examination Protocol
by Albrecht Günther, Anne Gunkel, Christian Geis, Dirk Brämer, Martin Brauer, Claus Doerfel, Michael Fritzenwanger, Martin Freesmeyer, Thomas Winkens, Robert Drescher and Anke Werner
Diagnostics 2025, 15(21), 2734; https://doi.org/10.3390/diagnostics15212734 - 28 Oct 2025
Viewed by 1117
Abstract
Background: In addition to clinical examinations, confirmatory investigations are frequently performed to determine brain death (BD). Among other perfusion tests, brain perfusion scintigraphy (BPS) has been shown to be a reliable tool for the detection of brain circulatory arrest, particularly in cases with [...] Read more.
Background: In addition to clinical examinations, confirmatory investigations are frequently performed to determine brain death (BD). Among other perfusion tests, brain perfusion scintigraphy (BPS) has been shown to be a reliable tool for the detection of brain circulatory arrest, particularly in cases with inconclusive clinical status or potential pharmacological interactions. Methods: Evaluation for brain death included standardized clinical examinations by two experienced neuro-intensive medicine specialists, followed by ancillary brain perfusion tests. BPS with the lipophilic tracer 99mTc-hexamethylpropyleneamine oxime (HMPAO) was performed according to a standardized protocol. Imaging results, additional confirmatory test results, as well as clinical parameters were prospectively recorded. Results: BPS was performed in 30 patients (18 male, 12 female; median age 55.5 years, range 0.1–79.8 years). Eight patients underwent decompressive craniectomy (DC) prior to BD evaluation, three patients were supported by veno-arterial extracorporeal membrane oxygenation (vaECMO), and one patient by a left ventricular assist device (LVAD). The median interval between the initial brain-damaging event and BPS was 4.0 days (range 1–18 days). BPS demonstrated brain perfusion cessation in all patients. A concomitant single-photon emission computed tomography (SPECT) was required in one patient. There were no technical failures requiring a re-examination. Conclusions: BPS is a feasible, safe, and technically robust confirmatory test in BD diagnosis. BPS yielded unambiguous results, particularly in cases with inconclusive results of other ancillary tests, in neonates, young children and patients after DC. It is applicable to patients supported by LVAD and vaECMO. Full article
(This article belongs to the Special Issue Neurological Disorders: Diagnosis and Management)
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18 pages, 4029 KB  
Article
Effects of the Orifice and Absorber Grid Designs on Coolant Mixing at the Inlet of an RITM-Type SMR Fuel Assembly
by Anton Riazanov, Sergei Dmitriev, Denis Doronkov, Aleksandr Dobrov, Aleksey Pronin, Dmitriy Solntsev, Tatiana Demkina, Daniil Kuritsin and Danil Nikolaev
Fluids 2025, 10(11), 278; https://doi.org/10.3390/fluids10110278 - 24 Oct 2025
Cited by 1 | Viewed by 444
Abstract
This article presents the results of an experimental study on the hydrodynamics of the coolant at the inlet of the fuel assembly in the RITM reactor core. The importance of these studies stems from the significant impact that inlet flow conditions have on [...] Read more.
This article presents the results of an experimental study on the hydrodynamics of the coolant at the inlet of the fuel assembly in the RITM reactor core. The importance of these studies stems from the significant impact that inlet flow conditions have on the flow structure within a fuel assembly. A significant variation in axial velocity and local flow rates can greatly affect the heat exchange processes within the fuel assembly, potentially compromising the safety of the core operation. The aim of this work was to investigate the effect of different designs of orifice inlet devices and integrated absorber grids on the flow pattern of the coolant in the rod bundle of the fuel assembly. To achieve this goal, experiments were conducted on a scaled model of the inlet section of the fuel assembly, which included all the structural components of the actual fuel assembly, from the orifice inlet device to the second spacer grids. The test model was scaled down by a factor of 5.8 from the original fuel assembly. Two methods were used to study the hydrodynamics: dynamic pressure probe measurements and the tracer injection technique. The studies were conducted in several sections along the length of the test model, covering its entire cross-section. The choice of measurement locations was determined by the design features of the test model. The loss coefficient (K) of the orifice inlet device in fully open and maximally closed positions was experimentally determined. The features of the coolant flow at the inlet of the fuel assembly were visualized using axial velocity plots in cross-sections, as well as concentration distribution plots for the injected tracer. The geometry of the inlet orifice device at the fuel assembly has a significant impact on the pattern of axial flow velocity up to the center of the fuel bundle, between the first and second spacing grids. Two zones of low axial velocity are created at the edges of the fuel element cover, parallel to the mounting plates, at the entrance to the fuel bundle. These unevennesses in the axial speed are evened out before reaching the second grid. The attachment plates of the fuel elements to the diffuser greatly influence the intensity and direction of flow mixing. A comparative analysis of the effectiveness of two types of integrated absorber grids was performed. The experimental results were used to justify design modifications of individual elements of the fuel assembly and to validate the hydraulic performance of new core designs. Additionally, the experimental data can be used to validate CFD codes. Full article
(This article belongs to the Special Issue Heat Transfer in the Industry)
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25 pages, 12285 KB  
Article
Integrated Geophysical Hydrogeological Characterization of Fault Systems in Sandstone-Hosted Uranium In Situ Leaching: A Case Study of the K1b2 Ore Horizon, Bayin Gobi Basin
by Ke He, Yuan Yuan, Yue Sheng and Hongxing Li
Processes 2025, 13(10), 3313; https://doi.org/10.3390/pr13103313 - 16 Oct 2025
Viewed by 631
Abstract
This study presents an integrated geophysical and hydrogeological characterization of fault systems in the sandstone-hosted uranium deposit within the K1b2 Ore Horizon of the Bayin Gobi Basin. Employing 3D seismic exploration with 64-fold coverage and advanced attribute analysis techniques (including [...] Read more.
This study presents an integrated geophysical and hydrogeological characterization of fault systems in the sandstone-hosted uranium deposit within the K1b2 Ore Horizon of the Bayin Gobi Basin. Employing 3D seismic exploration with 64-fold coverage and advanced attribute analysis techniques (including coherence volumes, ant-tracking algorithms, and LOW_FRQ spectral attenuation), the research identified 18 normal faults with vertical displacements up to 21 m, demonstrating a predominant NE-oriented structural pattern consistent with regional tectonic features. The fracture network analysis reveals anisotropic permeability distributions (31.6:1–41.4:1 ratios) with microfracture densities reaching 3.2 fractures/km2 in the central and northwestern sectors, significantly influencing lixiviant flow paths as validated by tracer tests showing 22° NE flow deviations. Hydrogeological assessments indicate that fault zones such as F11 exhibit 3.1 times higher transmissivity (5.3 m2/d) compared to non-fault areas, directly impacting in situ leaching (ISL) efficiency through preferential fluid pathways. The study establishes a technical framework for fracture system monitoring and hydraulic performance evaluation, addressing critical challenges in ISL operations, including undetected fault extensions that caused lixiviant leakage incidents in field cases. These findings provide essential geological foundations for optimizing well placement and leaching zone design in structurally complex sandstone-hosted uranium deposits. The methodology combines seismic attribute analysis with hydrogeological validation, demonstrating how fault systems control fluid flow dynamics in ISL operations. The results highlight the importance of integrated geophysical approaches for accurate structural characterization and operational risk mitigation in uranium mining. Full article
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