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Applications for Transition-Metal Chemistry in Contrast-Enhanced Magnetic Resonance Imaging

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TLDR
This Viewpoint highlights how recent advances in transition-metal chemistry are leading the way for a new generation of MRI contrast agents.
Abstract
Contrast-enhanced magnetic resonance imaging (MRI) is an indispensable tool for diagnostic medicine. However, safety concerns related to gadolinium in commercial MRI contrast agents have emerged in recent years. For patients suffering from severe renal impairment, there is an important unmet medical need to perform contrast-enhanced MRI without gadolinium. There are also concerns over the long-term effects of retained gadolinium within the general patient population. Demand for gadolinium-free MRI contrast agents is driving a new wave of inorganic chemistry innovation as researchers explore paramagnetic transition-metal complexes as potential alternatives. Furthermore, advances in personalized care making use of molecular-level information have motivated inorganic chemists to develop MRI contrast agents that can detect pathologic changes at the molecular level. Recent studies have highlighted how reaction-based modulation of transition-metal paramagnetism offers a highly effective mechanism to achieve MRI contrast enhancement that is specific to biochemical processes. This Viewpoint highlights how recent advances in transition-metal chemistry are leading the way for a new generation of MRI contrast agents.

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Citations
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Positron Emission Tomography-Magnetic Resonance Imaging Pharmacokinetics, In Vivo Biodistribution, and Whole-Body Elimination of Mn-PyC3A.

TL;DR: Dynamic PET-MRI data demonstrate that both Mn-PyC3A and Mn-DPDP were eliminated by mixed renal and hepatobiliary elimination but that a greater fraction of [Mn]Mn- PyC3a was eliminated by renal filtration.
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Dinuclear Fe(III) Hydroxypropyl-Appended Macrocyclic Complexes as MRI Probes.

TL;DR: In this paper, four high-spin Fe(III) macrocyclic complexes, including three dinuclear and one mononuclear complex, were prepared toward the development of more effective iron-based magnetic resonance imaging (MRI) contrast agents.
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Exceptional Manganese(II) Stability and Manganese(II)/Zinc(II) Selectivity with Rigid Polydentate Ligands

TL;DR: Two new bispidine derivatives are reported, which provide rigid and large coordination cavities that perfectly match the size of Mn II, yielding eight-coordinate Mn II complexes with record stabilities and inertness.
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Distinct Coordination Chemistry of Fe(III)-Based MRI Probes.

TL;DR: In this paper , the authors describe different classes of Fe(III) MRI probes with a focus on macrocyclic complexes and multinuclear complexes such as self-assembled metal organic polyhedra (MOP).
References
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Journal ArticleDOI

Stable and Inert Mn(II)-Based and pH-Responsive Contrast Agents

TL;DR: The first example of a Mn(II) complex that can be activated by changing the pH of its local environment is reported, finding the PC2A-EA ligand with an ethylamine pendant arm to form thermodynamically stable and kinetically inert complex.
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Hexameric Mn(II) Dendrimer as MRI Contrast Agent

TL;DR: This Mn(II) containing dendrimer represents a potential alternative to Gd-based contrast agents, especially in patients with chronic kidney disease where the use of current Gd -based agents may be contraindicated.
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A Janus Chelator Enables Biochemically Responsive MRI Contrast with Exceptional Dynamic Range

TL;DR: A new biochemically responsive Mn-based MRI contrast agent that provides a 9-fold change in relaxivity via switching between the Mn3+ and Mn2+ oxidation states and is promoted by a "Janus" ligand that isomerizes between binding modes that favor Mn3 or Mn2+.
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Detection of in vivo enzyme activity with CatalyCEST MRI

TL;DR: The purpose of this study was to investigate the feasibility of in vivo catalyCEST MRI and to compare the detection of an enzyme‐responsive chemical exchange saturation transfer agent with an unresponsive “control” CEST agent that accounts for other conditions that influence CEST.
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Can the theoretical fitting of the proton-nuclear-magnetic-relaxation-dispersion (proton NMRD) curves of paramagnetic complexes be improved by independent measurement of their self-diffusion coefficients?

TL;DR: In this paper, the self-diffusion coefficients of various lanthanum(III) diamagnetic analogues of open-chain and macrocyclic complexes of gadolinium used as MRI contrast agents were determined in dilute aqueous solutions (3-31mM) by pulsed-field-gradient (PFG) high-resolution 1H-NMR spectroscopy.
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