High Relaxivity Confined to a Small Molecular Space: A Metallostar‐Based, Potential MRI Contrast Agent

Livramento, João Bruno; Tóth, Éva; Sour, Angélique; Borel, Alain; Merbach, André E.; Ruloff, Robert

doi:10.1002/anie.200461875

Cited by 150 publications

(90 citation statements)

References 9 publications

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“…Thus, the formation of the (GdL2) 2 Zn species with one Zn 2+ ion bound to two GdL2 chelates results in a correspondingly longer rotational correlation time and a higher relaxivity value. [29][30][31][32] T 1 -weighted images were recorded by using a commercial 0.55 T (23 MHz) magnet. As depicted in Figure 1, the imaging contrast of GdL2 (0.1 mm) is clearly improved by the addition of 0.5 equiv.…”

Section: Resultsmentioning

confidence: 99%

Zn²⁺‐Responsive Bimodal Magnetic Resonance Imaging and Fluorescence Imaging Agents and Their Interaction with Human Serum Albumin

Luo

Chen

2014

Eur J Inorg Chem

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The gadolinium(III) complexes GdL1 and GdL2 were designed as Zn 2+ -responsive bimodal magnetic resonance imaging (MRI) and fluorescence imaging probes. Upon binding to Zn 2+ ions, GdL1 exhibits a bidentate or tridentate mode to form heterodinuclear GdL1Zn or heterotrinuclear (GdL1) 2 Zn, whereas GdL2 binds to the Zn 2+ ion only in a bidentate mode to form (GdL2) 2 Zn. The gadolinium(III) complexes derived from both H 3 L1 and H 3 L2 exhibit remarkable interactions with human serum albumin (HSA) at both site I and site II, which result in significant enhancements of the relaxivity and remarkable improvements of T 1 -weighted imaging contrast. In the presence of HSA, both the relaxivity (r 1 ) and fluo-

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Section: Resultsmentioning

confidence: 99%

Zn²⁺‐Responsive Bimodal Magnetic Resonance Imaging and Fluorescence Imaging Agents and Their Interaction with Human Serum Albumin

Luo

Chen

2014

Eur J Inorg Chem

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“…The other approach is to make the molecule larger by linking multiple chelates together in a fairly rigid fashion, Figure 9b. There are several examples of this approach and increased high field relaxivity has been noted (15,17,56,57). …”

Section: Discussionmentioning

confidence: 99%

Influence of molecular parameters and increasing magnetic field strength on relaxivity of gadolinium‐ and manganese‐based T₁ contrast agents

Caravan

Farrar

Frullano

et al. 2009

Contrast Media & Molecular

467

608

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Simulations were performed to understand the relative contributions of molecular parameters to longitudinal (r1) and transverse (r2) relaxivity as a function of field, and to obtain theoretical relaxivity maxima over a range of fields to appreciate what relaxivities can be achieved experimentally. The field dependent relaxivity of a panel of gadolinium and manganese complexes with different molecular parameters: water exchange rates, rotational correlation times, hydration state, etc were measured to confirm that measured relaxivities were consistent with theory. The design tenets previously stressed for optimizing r1 at low fields (very slow rotational motion; chelate immobilized by protein binding; optimized water exchange rate) do not apply at higher fields. At 1.5T and higher fields, an intermediate rotational correlation time is desired (0.5 – 4 ns), while water exchange rate is not as critical to achieving a high r1. For targeted applications it is recommended to tether a multimer of metal chelates to a protein-targeting group via a long flexible linker to decouple the slow motion of the protein from the water(s) bound to the metal ions. Per ion relaxivities of 80, 45, and 18 mM−1s−1 at 1.5, 3, and 9.4T respectively are feasible for Gd3+ and Mn2+ complexes.

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“…This technique does cover several decades in frequency, however the data in the literature usually stop at about ~60 MHz. Thus, relaxivity measurements at fields higher than 1.5 T are usually done at discrete magnetic field values on different NMR spectrometers, or on different high-field MR scanners1819. Such time consuming measurements provide information for the efficiency of the relaxation enhancement by contrast agents at discrete values of the magnetic field only, and cannot be routinely performed for the design of new contrast agents in a chemical laboratory having a single high-field NMR magnet.…”

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confidence: 99%

Ultra-wide range field-dependent measurements of the relaxivity of Gd1−xEuxVO4 nanoparticle contrast agents using a mechanical sample-shuttling relaxometer

Chou

Abdesselem

Bouzigues

et al. 2017

Sci Rep

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The current trend for Magnetic Resonance Imaging points towards higher magnetic fields. Even though sensitivity and resolution are increased in stronger fields, T1 contrast is often reduced, and this represents a challenge for contrast agent design. Field-dependent measurements of relaxivity are thus important to characterize contrast agents. At present, the field-dependent curves of relaxivity are usually carried out in the field range of 0 T to 2 T, using fast field cycling relaxometers. Here, we employ a high-speed sample shuttling device to switch the magnetic fields experienced by the nuclei between virtually zero field, and the center of any commercial spectrometer. We apply this approach on rare-earth (mixed Gadolinium-Europium) vanadate nanoparticles, and obtain the dispersion curves from very low magnetic field up to 11.7 T. In contrast to the relaxivity profiles of Gd chelates, commonly used for clinical applications, which display a plateau and then a decrease for increasing magnetic fields, these nanoparticles provide maximum contrast enhancement for magnetic fields around 1–1.5 T. These field-dependent curves are fitted using the so-called Magnetic Particle (MP) model and the extracted parameters discussed as a function of particle size and composition. We finally comment on the new possibilities offered by this approach.

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High Relaxivity Confined to a Small Molecular Space: A Metallostar‐Based, Potential MRI Contrast Agent

Cited by 150 publications

References 9 publications

Zn²⁺‐Responsive Bimodal Magnetic Resonance Imaging and Fluorescence Imaging Agents and Their Interaction with Human Serum Albumin

Zn²⁺‐Responsive Bimodal Magnetic Resonance Imaging and Fluorescence Imaging Agents and Their Interaction with Human Serum Albumin

Influence of molecular parameters and increasing magnetic field strength on relaxivity of gadolinium‐ and manganese‐based T₁ contrast agents

Ultra-wide range field-dependent measurements of the relaxivity of Gd1−xEuxVO4 nanoparticle contrast agents using a mechanical sample-shuttling relaxometer

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High Relaxivity Confined to a Small Molecular Space: A Metallostar‐Based, Potential MRI Contrast Agent

Cited by 150 publications

References 9 publications

Zn2+‐Responsive Bimodal Magnetic Resonance Imaging and Fluorescence Imaging Agents and Their Interaction with Human Serum Albumin

Zn2+‐Responsive Bimodal Magnetic Resonance Imaging and Fluorescence Imaging Agents and Their Interaction with Human Serum Albumin

Influence of molecular parameters and increasing magnetic field strength on relaxivity of gadolinium‐ and manganese‐based T1 contrast agents

Ultra-wide range field-dependent measurements of the relaxivity of Gd1−xEuxVO4 nanoparticle contrast agents using a mechanical sample-shuttling relaxometer

Contact Info

Product

Resources

About

Zn²⁺‐Responsive Bimodal Magnetic Resonance Imaging and Fluorescence Imaging Agents and Their Interaction with Human Serum Albumin

Zn²⁺‐Responsive Bimodal Magnetic Resonance Imaging and Fluorescence Imaging Agents and Their Interaction with Human Serum Albumin

Influence of molecular parameters and increasing magnetic field strength on relaxivity of gadolinium‐ and manganese‐based T₁ contrast agents