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      Phosphorus‐Containing Polymeric Zwitterion: A Pioneering Bioresponsive Probe for 31 P‐Magnetic Resonance Imaging

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          Abstract

          31 P-magnetic resonance (MR) is an important diagnostic technique currently used for tissue metabolites assessing, but it also has great potential for visualizing the internal body structures. However, due to the low physiological level of phosphorus-containing biomolecules, precise imaging requires the administration of an exogenous probe. Herein, this work describes the synthesis and MR characterization of a pioneering metal-free 31 P-MR probe based on phosphorus-containing polymeric zwitterion. The developed probe (pTMPC) is a well-defined water-soluble macromolecule characterized by a high content of naturally rare phosphorothioate groups providing a high-intensity 31 P-MR signal clearly distinguishable from biological background both in vitro and in vitro. In addition, pTMPC can serve as a sensitive 31 P-MR sensor of pathological conditions in vivo because it undergoes oxidation-induced structural changes in the presence of reactive oxygen species (ROS). Add to this the favorable 1 H and 31 P T1 /T2 relaxation times and biocompatibility, pTMPC represents a conceptually new diagnostic, whose discovery opens up new possibilities in the field of 31 P-MR spectroscopy and imaging.

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          Chemistry of MRI Contrast Agents: Current Challenges and New Frontiers

          Tens of millions of contrast-enhanced magnetic resonance imaging (MRI) exams are performed annually around the world. The contrast agents, which improve diagnostic accuracy, are almost exclusively small, hydrophilic gadolinium(III) based chelates. In recent years concerns have arisen surrounding the long-term safety of these compounds, and this has spurred research into alternatives. There has also been a push to develop new molecularly targeted contrast agents or agents that can sense pathological changes in the local environment. This comprehensive review describes the state of the art of clinically approved contrast agents, their mechanism of action, and factors influencing their safety. From there we describe different mechanisms of generating MR image contrast such as relaxation, chemical exchange saturation transfer, and direct detection and the types of molecules that are effective for these purposes. Next we describe efforts to make safer contrast agents either by increasing relaxivity, increasing resistance to metal ion release, or by moving to gadolinium(III)-free alternatives. Finally we survey approaches to make contrast agents more specific for pathology either by direct biochemical targeting or by the design of responsive or activatable contrast agents.
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            Polymer–drug conjugate therapeutics: advances, insights and prospects

            Polymer-drug conjugates have long been a mainstay of the drug delivery field, with several conjugates successfully translated into clinical practice. The conjugation of therapeutic agents to polymeric carriers, such as polyethylene glycol, offers several advantages, including improved drug solubilization, prolonged circulation, reduced immunogenicity, controlled release and enhanced safety. In this Review, we discuss the rational design, physicochemical characteristics and recent advances in the development of different classes of polymer-drug conjugates, including polymer-protein and polymer-small-molecule drug conjugates, dendrimers, polymer nanoparticles and multifunctional systems. Current obstacles hampering the clinical translation of polymer-drug conjugate therapeutics and future prospects are also presented.
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              High signal intensity in the dentate nucleus and globus pallidus on unenhanced T1-weighted MR images: relationship with increasing cumulative dose of a gadolinium-based contrast material.

              To explore any correlation between the number of previous gadolinium-based contrast material administrations and high signal intensity (SI) in the dentate nucleus and globus pallidus on unenhanced T1-weighted magnetic resonance (MR) images. The institutional review board approved this study, waiving the requirement to obtain written informed consent. A group of 381 consecutive patients who had undergone brain MR imaging was identified for cross-sectional analysis. For longitudinal analysis, 19 patients who had undergone at least six contrast-enhanced examinations were compared with 16 patients who had undergone at least six unenhanced examinations. The mean SIs of the dentate nucleus, pons, globus pallidus, and thalamus were measured on unenhanced T1-weighted images. The dentate nucleus-to-pons SI ratio was calculated by dividing the SI in the dentate nucleus by that in the pons, and the globus pallidus-to-thalamus SI ratio was calculated by dividing the SI in the globus pallidus by that in the thalamus. Stepwise regression analysis was undertaken in the consecutive patient group to detect any relationship between the dentate nucleus-to-pons or globus pallidus-to-thalamus SI ratio and previous gadolinium-based contrast material administration or other factors. A random coefficient model was used to evaluate for longitudinal analysis. The dentate nucleus-to-pons SI ratio showed a significant correlation with the number of previous gadolinium-based contrast material administrations (P < .001; regression coefficient, 0.010; 95% confidence interval [CI]: 0.009, 0.011; standardized regression coefficient, 0.695). The globus pallidus-to-thalamus SI ratio showed a significant correlation with the number of previous gadolinium-based contrast material administrations (P < .001; regression coefficient, 0.004; 95% CI: 0.002, 0.006; standardized regression coefficient, 0.288), radiation therapy (P = .009; regression coefficient, -0.014; 95% CI: -0.025, -0.004; standardized regression coefficient, -0.151), and liver function (P = .031; regression coefficient, 0.023; 95% CI: 0.002, 0.044; standardized regression coefficient, 0.107). The dentate nucleus-to-pons and globus pallidus-to-thalamus SI ratios in patients who had undergone contrast-enhanced examinations were significantly greater than those of patients who had undergone unenhanced examinations (P < .001 for both). High SI in the dentate nucleus and globus pallidus on unenhanced T1-weighted images may be a consequence of the number of previous gadolinium-based contrast material administrations. RSNA, 2013
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                Author and article information

                Contributors
                Journal
                Macromolecular Bioscience
                Macromolecular Bioscience
                Wiley
                1616-5187
                1616-5195
                May 2022
                March 10 2022
                May 2022
                : 22
                : 5
                : 2100523
                Affiliations
                [1 ]Institute of Macromolecular Chemistry Czech Academy of Sciences Heyrovského nám. 2 Prague 162 06 Czech Republic
                [2 ]Faculty of Chemical Technology The University of Chemistry and Technology Technická 5 Prague 166 28 Czech Republic
                [3 ]Institute for Clinical and Experimental Medicine Vídeňská 1958/9 Prague 140 21 Czech Republic
                [4 ]First Faculty of Medicine Charles University Kateřinská 1660/32 Prague 121 08 Czech Republic
                [5 ]Faculty of Mechatronics Informatics and Interdisciplinary Studies Technical University of Liberec Hálkova 917 Liberec 461 17 Czech Republic
                [6 ]Institute of Biotechnology Czech Academy of Sciences Průmyslová 595 Vestec 252 50 Czech Republic
                [7 ]Faculty of Science Jan Evangelista Purkyně University in Ústí nad Labem Pasteurova 1 Ústí nad Labem 400 96 Czech Republic
                [8 ]Faculty of Health Studies Technical University of Liberec Studentská 1402/2 Liberec 461 17 Czech Republic
                Article
                10.1002/mabi.202100523
                35246950
                ad730d64-2eda-4036-b34f-c47b176a803c
                © 2022

                http://onlinelibrary.wiley.com/termsAndConditions#vor

                http://doi.wiley.com/10.1002/tdm_license_1.1

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