Bracco (Italy)

The substitution of carboxylate donors with neutral amide groups is a well-established approach for tuning charge distribution and hydration properties in metal chelates; however, its influence on Fe(III) systems has remained largely unexplored. Here, we report two CDTA-derived ligands incorporating one or two secondary butylamide substituents (CD3A-BA and CD2A-BA₂) and comprehensively characterize their Fe(III) complexes using potentiometry, capillary zone electrophoresis, UV-Vis spectrophotometry, transchelation assays (with HBED and human serum transferrin), 1H NMRD, variable-temperature 17O NMR, and in vitro cytotoxicity tests. Amide incorporation decreases ligand basicity and leads to reduced complex stability and kinetic inertness compared to the parent CDTA framework. Nevertheless, the new Fe(III) complexes retain strong metal affinity and remain monohydrated under physiologically relevant conditions. Progressive amide substitution systematically slows inner-sphere water exchange, consistent with the higher residual positive charge of the complexes. Despite this, relaxivity in media mimicking physiological conditions remains unchanged, with negligible protein binding and no detectable Fe(III) release. Cellular assays confirm an absence of cytotoxicity at the tested concentrations. Collectively, these findings elucidate how secondary-amide substitution governs stability, reactivity, and hydration dynamics in Fe(III)-CDTA derivatives, offering valuable insights for the rational design of Fe(III)-based MRI contrast agents.

treatment of obstructive coronary artery disease (CAD) requires accurate planning to ensure effective revascularization and full restoration of myocardial perfusion. In this study, we introduce Virtual PCI, a novel computational tool designed to support pre-operative planning of Percutaneous Coronary Intervention (PCI) by predicting the hemodynamic consequences of selected revascularization treatments. the tool leverages a fully personalized 3D multiscale perfusion model, calibrated using pre-intervention stress CT perfusion (CTP) imaging, to simulate the hemodynamic impact of different revascularization strategies in terms of post-intervention stress myocardial blood flow (MBF) and FFR. The computational framework is also capable of computing the FFR index. We conduct a validation study on patients treated with elective PCI and compare model predictions with dynamic stress CTP at follow-up. the validation study demonstrates high accuracy in predicting post-PCI myocardial perfusion, including potential residual ischemia and cardiac mass at ischemic risk. Through an integrated analysis with FFR, the tool shows potential for its prospective use, identifying in two patients optimal treatment strategies and, in one case, outperforming the executed revascularization in reduction of ischemic burden. Virtual PCI enables the prediction of post-PCI myocardial blood flow (MBF) and FFR, offering a comprehensive assessment of treatment outcomes to identify the best revascularization option from the hemodynamic standpoint. since it relies solely on non-invasive imaging (cCTA, stress-CTP), Virtual PCI can be integrated early in the diagnostic workflow, providing cardiologists with a powerful, patient-specific tool to optimize PCI planning.

Abstract Objective treatment of obstructive coronary artery disease (CAD) requires accurate planning to ensure effective revascularization and full restoration of myocardial perfusion. In this study, we introduce Virtual PCI, a novel computational tool designed to support pre-operative planning of Percutaneous Coronary Intervention (PCI) by predicting the hemodynamic consequences of selected revascularization treatments. Methods the tool leverages a fully personalized 3D multiscale perfusion model, calibrated using pre-intervention stress CT perfusion (CTP) imaging, to simulate the hemodynamic impact of different revascularization strategies in terms of post-intervention stress myocardial blood flow (MBF) and FFR. The computational framework is also capable of computing the FFR index. We conduct a validation study on patients treated with elective PCI and compare model predictions with dynamic stress CTP at follow-up. Results the validation study demonstrates high accuracy in predicting post-PCI myocardial perfusion, including potential residual ischemia and cardiac mass at ischemic risk. Through an integrated analysis with FFR, the tool shows potential for its prospective use, identifying in two patients optimal treatment strategies and, in one case, outperforming the executed revascularization in reduction of ischemic burden. Conclusions Virtual PCI enables the prediction of post-PCI myocardial blood flow (MBF) and FFR, offering a comprehensive assessment of treatment outcomes to identify the best revascularization option from the hemodynamic standpoint. Significance since it relies solely on non-invasive imaging (cCTA, stress-CTP), Virtual PCI can be integrated early in the diagnostic workflow, providing cardiologists with a powerful, patient-specific tool to optimize PCI planning.

Advanced-stage sarcomas pose a major challenge in oncology, as they are often resistant to conventional therapies and associated with poor prognosis. CAR-based cellular immunotherapy is emerging as a very promising therapeutic option; however, clinically relevant animal models are urgently needed to accelerate the clinical development of these approaches. B7-H3 molecule, due to its low expression in normal tissue, high prevalence in multiple human cancers, and association with cancer stemness and aggressiveness, represents one of the most attractive targets for CAR-immunotherapy. In this study, we established a preclinical cellular immunotherapy platform based on canine cytokine-induced killer cells (CIK) redirected by an antihuman B7-H3 CAR against canine sarcoma cells and 3D sarcoma spheroids. B7-H3 was consistently detected across all analyzed canine sarcoma subtypes, including osteosarcoma, soft tissue sarcoma, and hemangiosarcoma, although with variable levels of expression intensity. We successfully generated canine B7-H3-CAR.CIK, achieving a mean CAR expression of 39% ± 2 with an immune phenotype unmodified (NTD) control (CD3 = 92% ± 3, CD8 = 87% ± 7; CD4 = 49% ± 5; CD5 = 77% ± 0.1; NKp46 = 83% ± 5). Canine B7-H3-CAR.CIK efficiently killed canine sarcoma cell lines compared with NTD.CIK, even at low effector/target (E/T) ratios (B7-H3-CAR.CIK: 45% vs 8%; E:T 1:1; 48 h; N = 7, n = 8; p < 0.0001), and demonstrated significant cytotoxicity against 3D sarcoma spheroids (58% vs 13%; E:T 2:1; 48 h; N = 3, n = 4; p < 0.01). Our findings establish a clinically relevant and translationally valuable platform for evaluating B7-H3-CAR.CIK therapy in dogs with incurable sarcomas, providing a bridge toward the development of novel CAR-based immunotherapies for human incurable sarcomas.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00262-025-04163-4.

Artificial intelligence (AI) methods have established themselves in cardiovascular magnetic resonance (CMR) as automated quantification tools for ventricular volumes, function, and myocardial tissue characterization. Quality assurance approaches focus on measuring and controlling AI-expert differences but there is a need for tools that better communicate reliability and agreement. This study introduces the Verity plot, a novel statistical visualization that communicates the reliability of quantitative parameters (QP) with clear agreement criteria and descriptive statistics. Tolerance ranges for the acceptability of the bias and variance of AI-expert differences were derived from intra- and interreader evaluations. AI-expert agreement was defined by bias confidence and variance tolerance intervals being within bias and variance tolerance ranges. A reliability plot was designed to communicate this statistical test for agreement. Verity plots merge reliability plots with density and a scatter plot to illustrate AI-expert differences. Their utility was compared against Correlation, Box and Bland-Altman plots. Bias and variance tolerance ranges were established for volume, function, and myocardial tissue characterization QPs. Verity plots provided insights into statstistcal properties, outlier detection, and parametric test assumptions, outperforming Correlation, Box and Bland-Altman plots. Additionally, they offered a framework for determining the acceptability of AI-expert bias and variance. Verity plots offer markers for bias, variance, trends and outliers, in addition to deciding AI quantification acceptability. The plots were successfully applied to various AI methods in CMR and decisively communicated AI-expert agreement.

• Improvement of the iopamidol adsorption systems • Use of new technologies to enhance adsorption capacity of the activated carbon • New compact devices for wastewater treatment to be applied in industrial scale • Comparison of new systems with conventional ones for iopamidol removal Conventional wastewater treatment methods are ineffective at degrading Iopamidol (IPM), allowing this pharmaceutical compound to penetrate aquatic systems, raising concerns about potential ecological impacts. Adsorption using granular activated carbon (GAC) represents an effective technique for IPM removal from water. This study focuses on the development of innovative technological approaches for the effective removal of IPM using Rotating Packed Beds (RPBs) and ultrasound enhancement techniques. These methods not only promise improved efficiency in pollutant removal but are also applicable on an industrial scale, making them significant advancements in wastewater treatment technologies. RPB system is investigated to replace the common impeller in batch system using the centrifugal acceleration to intensify the mass transfer processes. At the same time, the application of ultrasounds in a continuous flow system can result in process intensification increasing the productivity with lower impact on the environment and this dynamic system enables an evaluation of the adsorbent saturation in relation to the space, time and length of the adsorption column. In this paper the intensification of IPM adsorption was performed using the RPB and a continuous flow system in presence of ultrasounds, an improvement of the conventional adsorption process of 13% and 64% respectively was shown.

Mesocyclic chelating agents such as AAZTA and its derivatives have been recently reported to overcome the relatively low thermodynamic stability of metal complexes of acyclic chelating agents and the slow complexation kinetics of macrocyclic chelating agents. This work reports the preparation of a spirobicyclic hexadentate AAZTA-like chelating agent (TRASUTA) and the investigation of the thermodynamic, kinetic, and structural properties of the corresponding chelates with the PET-relevant Ga3+ and selected metal ions. A combination of analytical techniques allowed identification of a coordination isomerization process, involving the coordinating side arms and the inversion of a nitrogen atom and leading to lower thermodynamic and kinetic inertness with respect to mononuclear mesocyclic analogues. The bicyclic system of TRASUTA retains significant dynamics despite the conformational constraint imposed by the spiro-fusion, resulting in a lower stability of the corresponding metal chelates.

Background: Perivascular adipose tissue (PVAT) attenuation has emerged as a novel biomarker for identifying high-risk arterial plaques due to its association with inflammation. Recognizing the systemic nature of atherosclerosis and its link with major cardiovascular events in coronary disease, this study evaluated PVAT attenuation in the peripheral arteries using CT imaging to expand the understanding of its diagnostic and prognostic potential. Methods: a retrospective analysis of 53 consecutive patients who underwent CT angiography, examining PVAT density across five primary peripheral arterial segments. A 5 mm region of interest adjacent to the vascular wall was analyzed by two blinded readers, with reproducibility coefficients calculated to determine the reliability of the measurements. For the statistical analyses, mean values were derived from these measurements. The patients were stratified into four groups based on the degree of arterial stenosis: &lt;25%, 25–50%, 50–70%, and &gt;70%. PVAT density comparisons between these groups were performed using the Kruskal–Wallis test and the pairwise Mann–Whitney U test with Holm–Bonferroni correction for multiple comparisons. Results: the Kruskal–Wallis test revealed statistically significant disparities in PVAT density across the categorically differentiated stenosis groups (p &lt; 0.001), indicating an association between PVAT density and arterial stenosis severity. This association was especially pronounced in the external iliac, common femoral, superficial femoral, and popliteal arteries, where the p-values were consistently below 0.05. Subsequent pairwise analyses utilizing the Mann–Whitney U test with Holm–Bonferroni correction affirmed these findings, in particular for the external iliac, common femoral, superficial femoral and popliteal arteries (p &lt; 0.05). Conclusions: our findings reinforce the correlation between increased PVAT density and the degree of arterial stenosis, supporting the clinical value of PVAT as a non-invasive biomarker for cardiovascular risk stratification and potentially guiding therapeutic interventions.