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      Effect of gadolinium concentration on temperature change under magnetic field

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      PLoS ONE
      Public Library of Science

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          Abstract

          Gadolinium based contrast agents (GBCAs) were found to play a role in nephrogenic systemic fibrosis in patients with and without renal impairment. Therefore, preserving the structural stability of GBCAs to reduce their propensity to liberate Gd 3+ is of utmost importance. This study evaluates the effect of gadolinium concentration of GBCAs on solution temperature under magnetic fields. It is hypothesized that presence of gadolinium will lead to temperature changes of its solutions under magnetic field, and this change will depend on concentration. In this study, GBCAs were diluted to concentrations of 0.6, 1.2, 1.8, 2.4 mMol/L. A 10mL preparation in pure water, simulated body fluid (SBF), and plasma was scanned at 3T following a soft tissue neck protocol, and their temperatures were measured. Findings revealed that concentration of GBCA had significant effect on temperature change in all dilution media. Type of commercially available GBCA had an effect only in SFB and plasma. Evaluation of correlation between conditional stability constant (K cond) and temperature difference (ΔT) revealed that in water and SBF there exists a positive correlation between K cond and temperature variation. Collectively, GBCAs can cause local temperature variations when administered into patients, and can affect dissociation of gadolinium from its chelates, which should be investigated in a further study.

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          Recent developments in magnetocaloric materials

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            Primer on gadolinium chemistry.

            Gadolinium is widely known by all practitioners of magnetic resonance imaging (MRI) but few appreciate the basic solution chemistry of this trivalent lanthanide ion. Given the recent linkage between gadolinium contrast agents and nephrogenic systemic fibrosis, some basic chemistry of this ion must be more widely understood. This short primer on gadolinium chemistry is intended to provide the reader the background principles necessary to understand the basics of chelation chemistry, water hydration numbers, and the differences between thermodynamic stability and kinetic stability or inertness. We illustrate the fundamental importance of kinetic dissociation rates in determining gadolinium toxicity in vivo by presenting new data for a novel europium DOTA-tetraamide complex that is relatively unstable thermodynamically yet extraordinarily inert kinetically and also quite nontoxic. This, plus other literature evidence, forms the basis of the fundamental axiom that it is the kinetic stability of a gadolinium complex, not its thermodynamic stability, that determines its in vivo toxicity. J. Magn. Reson. Imaging 2009;30:1240-1248. (c) 2009 Wiley-Liss, Inc.
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              Efficiency, thermodynamic and kinetic stability of marketed gadolinium chelates and their possible clinical consequences: a critical review.

              Gadolinium-based contrast agents are widely used to enhance image contrast in magnetic resonance imaging (MRI) procedures. Over recent years, there has been a renewed interest in the physicochemical properties of gadolinium chelates used as contrast agents for MRI procedures, as it has been suggested that dechelation of these molecules could be involved in the mechanism of a recently described disease, namely nephrogenic systemic fibrosis (NSF). The aim of this paper is to discuss the structure-physicochemical properties relationships of marketed gadolinium chelates in regards to their biological consequences. Marketed gadolinium chelates can be classified according to key molecular design parameters: (a) nature of the chelating moiety: macrocyclic molecules in which Gd3+ is caged in the pre-organized cavity of the ligand, or linear open-chain molecules, (b) ionicity: the ionicity of the complex varies from neutral to tri-anionic agents, and (c) the presence or absence of an aromatic lipophilic residue responsible for protein binding. All these molecular characteristics have a profound impact on the physicochemical characteristics of the pharmaceutical solution such as osmolality, viscosity but also on their efficiency in relaxing water protons (relaxivity) and their biodistribution. These key molecular parameters can also explain why gadolinium chelates differ in terms of their thermodynamic stability constants and kinetic stability, as demonstrated by numerous in vitro and in vivo studies, resulting in various formulations of pharmaceutical solutions of marketed contrast agents. The concept of kinetic and thermodynamic stability is critically discussed as it remains a somewhat controversial topic, especially in predicting the amount of free gadolinium which may result from dechelation of chelates in physiological or pathological situations. A high kinetic stability provided by the macrocyclic structure combined with a high thermodynamic stability (reinforced by ionicity for macrocyclic chelates) will minimize the amount of free gadolinium released in tissue parenchymas.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: Visualization
                Role: ConceptualizationRole: InvestigationRole: Resources
                Role: Formal analysisRole: SupervisionRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                4 April 2019
                2019
                : 14
                : 4
                : e0214910
                Affiliations
                [1 ] Health Sciences University, Gulhane Medicine Faculty, Research and Education Hospital, Department of Radiology, Ankara, Turkey
                [2 ] Nazarbayev University, Chemical and Materials Engineering, Astana, Kazakhstan
                Henry Ford Health System, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0002-6337-8022
                Article
                PONE-D-19-02031
                10.1371/journal.pone.0214910
                6449068
                30947239
                dc01e0e5-4c54-4c1f-9700-a92cf440d18c
                © 2019 Arda et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 22 January 2019
                : 24 March 2019
                Page count
                Figures: 5, Tables: 2, Pages: 12
                Funding
                The authors received no specific funding for this work.
                Categories
                Research Article
                Physical Sciences
                Chemistry
                Chemical Elements
                Gadolinium
                Physical Sciences
                Physics
                Condensed Matter Physics
                Magnetism
                Magnetic Fields
                Physical Sciences
                Chemistry
                Chemical Compounds
                Salts
                Medicine and Health Sciences
                Diagnostic Medicine
                Diagnostic Radiology
                Magnetic Resonance Imaging
                Research and Analysis Methods
                Imaging Techniques
                Diagnostic Radiology
                Magnetic Resonance Imaging
                Medicine and Health Sciences
                Radiology and Imaging
                Diagnostic Radiology
                Magnetic Resonance Imaging
                Biology and Life Sciences
                Physiology
                Physiological Parameters
                Body Temperature
                Medicine and Health Sciences
                Physiology
                Physiological Parameters
                Body Temperature
                Physical Sciences
                Physics
                Thermodynamics
                Biology and Life Sciences
                Developmental Biology
                Fibrosis
                Medicine and Health Sciences
                Health Care
                Patients
                Custom metadata
                All relevant data are within the manuscript.

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                Uncategorized

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