A Redox‐Activated MRI Contrast Agent that Switches Between Paramagnetic and Diamagnetic States

Tsitovich, Pavel B.; Spernyak, Joseph A.; Morrow, Janet R.

doi:10.1002/anie.201306394

Cited by 104 publications

(133 citation statements)

References 21 publications

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“…One major strategy for MRI contrast enhancement focuses on valency changes of ions, which has been widely applied through using redox-activated chemical exchange saturation transfer (CEST) agents that can be detected by MRI. 85,86,209 As previously discussed, the valency of ions affects electron spin that in turn influences relaxation of water protons. Owing to its pH- and redox-responsive properties, MnO 2 can be reduced to Mn 2+ by GSH or H 2 O 2 /H +.51,53,210 For example, Chu et al .…”

Section: Strategies To Achieve High Relaxivity For Mri Contrast Enmentioning

confidence: 90%

“…Variable valencies ( e.g ., Mn 4+ /Mn 2+ ions, 54 Co 3+ /Co 2+ ions, 85 Eu 3+ /Eu 2+ ions 86 ) can endow these ions with tunable MRI performance under certain reducing or oxidative microenvironments, thus creating responsive MRI CAs for molecular imaging. 32 Mn 4+ -based NPs are widely used as pH or redoxresponsive MRI CAs because Mn 4+ ( J = 9/2, S = 3/2, L = 3) with negligible relaxation interactions can be easily reduced to Mn 2+ ( J = 5/2, S = 5/2, L = 0), which shows high MRI contrast capability according to the rules mentioned above.…”

Section: Basic Rules For Mri Contrast Agentsmentioning

confidence: 99%

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Engineering of inorganic nanoparticles as magnetic resonance imaging contrast agents

et al. 2017

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Magnetic resonance imaging (MRI) is a highly valuable non-invasive imaging tool owing to its exquisite soft tissue contrast, high spatial resolution, lack of ionizing radiation, and wide clinical applicability. Contrast agents (CAs) can be used to further enhance the sensitivity of MRI to obtain information-rich images. Recently, extensive research efforts have been focused on the design and synthesis of high-performance inorganic nanoparticle-based CAs to improve the quality and specificity of MRI. Herein, the basic rules, including the choice of metal ions, effect of electron motion on water relaxation, and involved mechanisms, of CAs for MRI have been elucidated in detail. In particular, various design principles, including size control, surface modification (e.g. organic ligand, silica shell, and inorganic nanolayers), and shape regulation, to impact relaxation of water molecules have been discussed in detail. Comprehensive understanding of how these factors work can guide the engineering of future inorganic nanoparticles with high relaxivity. Finally, we have summarized the currently available strategies and their mechanism for obtaining high-performance CAs and discussed the challenges and future developments of nanoparticulate CAs for clinical translation in MRI.

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Section: Strategies To Achieve High Relaxivity For Mri Contrast Enmentioning

confidence: 90%

Section: Basic Rules For Mri Contrast Agentsmentioning

confidence: 99%

Engineering of inorganic nanoparticles as magnetic resonance imaging contrast agents

et al. 2017

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“…13 Such studies are important for the identification of interactions that may interfere with CEST contrast. For example, binding of the complexes to macromolecules might modulate the CEST effect.…”

Section: Introductionmentioning

confidence: 99%

Seven-Coordinate Co^II, Fe^II and Six-Coordinate Ni^II Amide-Appended Macrocyclic Complexes as ParaCEST Agents in Biological Media

et al. 2014

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The solution chemistry and solid-state structures of the CoII, FeII, and NiII complexes of 7,13-bis(carbamoylmethyl)-1,4,10-trioxa-7,13-diazacyclopentadecane (L) are reported as members of a new class of paramagnetic chemical exchange saturation transfer (paraCEST) MRI contrast agents that contain transition metal ions. Crystallographic data show that nitrogen and oxygen donor atoms of the macrocyclic ligand coordinate to the metal ions to generate complexes with distorted pentagonal bipyramidal geometry for [Co(L)]Cl2·2H2O or [Fe(L)](CF3SO3)2. The NiII complex [Ni(L)](CF3SO3)2·H2O features a hexadentate ligand in a distorted octahedral geometry. The proton NMR spectra of all three complexes show highly dispersed and relatively sharp proton resonances. The complexes were further characterized by monitoring their dissociation under biologically relevant conditions including solutions containing phosphate and carbonate, ZnCl2, or acidic conditions. Solutions of the paraCEST agents in 20 mM N-(2-hydroxyethyl)piperazine-N′-ethanesulfonic acid (pH 7.4) and 100 mM NaCl showed highly shifted and intense CEST peaks at 59, 72, and 92 ppm away from bulk water for [Co(L)]2+, [Ni(L)]2+, and [Fe(L)]2+, respectively at 37 °C on a 11.7 T NMR spectrometer. CEST spectra with corresponding rate constants for proton exchange are reported in 4% agarose gel (w/w), rabbit serum, egg white, or buffered solutions. CEST phantoms of 4 mM complex in buffer, 4% agarose gel (w/w), or rabbit serum on a 4.7 T MRI scanner at 37 °C, are compared. The most substantial change was observed for the reactive [Ni(L)]2+, which showed reduced CEST contrast in rabbit serum and egg white. The complexes with the least highly shifted CEST peaks ([Co(L)]2+ and [Ni(L)]2+) showed a reduction in CEST contrast in 4% agarose gel (w/w) compared to that in buffered solutions, while the CEST effect for [Fe(L)]2+ in 4% agarose gel (w/w) was not substantially different.

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“…However, the present five ligands formed readily at room temperature in dichloromethane in the presence of activated molecular sieves. This success under milder conditions suggests that the heteroaromatic carbaldehydes based on thiophene (1-2) and furan (3)(4)(5) form thermodynamically more favorable mixed aminals than those from benzaldehyde derivatives (6)(7)(8). As the aminals were prone to rapid hydrolysis, as previously reported for 6-8, their isolation was precluded.…”

Section: Resultsmentioning

confidence: 82%

“…To the best of our knowledge, the examples of coordination compounds that respond to a change in their chemical composition by changing their magnetic properties do so only through gradual, reversible reactions. [2][3][4] We introduced a new probe concept that is based on low-spin iron(II) binary complexes [5][6][7] that undergo an irreversible reaction with the target analyte for high analyte specificity, optimal magnitude of signal change, and best adaptation to aqueous media. Our choice of the particular constitution of the complex has been motivated by the highly competitive nature of water as the solvent, the need to translate a chemical event into a readable signal, and the requirement to overcome the imposing strength of the chelate effect.…”

Section: Introductionmentioning

confidence: 99%

Spring‐Loaded Iron(II) Complexes as Magnetogenic Probes Reporting on a Chemical Analyte in Water

et al. 2015

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International audienceA new low-spin iron(II) triazacyclononane-based complex, selected from four different candidates, acts as a molecular probe that turns a diamagnetic aqueous sample into a paramagnetic one as a response to a chemical analyte. The four complexes are prepared by a highly convergent synthetic protocol and give precious insights into structure–activity relationship (SAR) tendencies

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A Redox‐Activated MRI Contrast Agent that Switches Between Paramagnetic and Diamagnetic States

Cited by 104 publications

References 21 publications

Engineering of inorganic nanoparticles as magnetic resonance imaging contrast agents

Engineering of inorganic nanoparticles as magnetic resonance imaging contrast agents

Seven-Coordinate Co^II, Fe^II and Six-Coordinate Ni^II Amide-Appended Macrocyclic Complexes as ParaCEST Agents in Biological Media

Spring‐Loaded Iron(II) Complexes as Magnetogenic Probes Reporting on a Chemical Analyte in Water

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A Redox‐Activated MRI Contrast Agent that Switches Between Paramagnetic and Diamagnetic States

Cited by 104 publications

References 21 publications

Engineering of inorganic nanoparticles as magnetic resonance imaging contrast agents

Engineering of inorganic nanoparticles as magnetic resonance imaging contrast agents

Seven-Coordinate CoII, FeII and Six-Coordinate NiII Amide-Appended Macrocyclic Complexes as ParaCEST Agents in Biological Media

Spring‐Loaded Iron(II) Complexes as Magnetogenic Probes Reporting on a Chemical Analyte in Water

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Seven-Coordinate Co^II, Fe^II and Six-Coordinate Ni^II Amide-Appended Macrocyclic Complexes as ParaCEST Agents in Biological Media