Gd(iii) chelates for MRI contrast agents: from high relaxivity to “smart”, from blood pool to blood–brain barrier permeable

Yang, Chang‐Tong; Chuang, Kai‐Hsiang

doi:10.1039/c2md00279e

Cited by 95 publications

(54 citation statements)

References 168 publications

(192 reference statements)

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“…Meanwhile, myriads of gadolinium(III) models will definitely serve as examples to follow. [31,83,84] In this spirit, Hasserodt presented an interesting model of the Fe 2+ system in which the cross-spin, initiated by various stimuli, led to the transformation of a diamagnetic, low-spin complex into a high-spin paramagnet. [85] Such off/on systems have been shown, for instance, to transform their coordination spheres by the action of chemical or enzymatic-reducing agents from 6N to 5N1O, thus leading to a significant signal in the MRI scanner.…”

Section: Discussionmentioning

confidence: 99%

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Iron(III) Contrast Agent Candidates for MRI: a Survey of the Structure–Effect Relationship in the Last 15 Years of Studies

Kuźnik

Wyskocka

2015

Eur J Inorg Chem

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Iron(III) complexes are under investigation as MRI contrast agents, and new challenges have delineated the way they are being developed. This review article describes the enhanced features that have been develolped in the last 15 years of research. The consequences of relaxation theory impose kinetic, thermodynamic, and structural requirements on the potential contrast agent. Iron, as an endogenous metal, might fulfil these expectations, so its specificity is discussed here. The

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Section: Discussionmentioning

confidence: 99%

“…[30] Finally, structural elements, the character of additional groups or moieties in the ligand, and the charge of the complex are considered in depth in the case of targeting an agent to the lymph or to crossing the cell membranes of the blood-brain barrier. [31] …”

Section: Contrast Agent Designmentioning

confidence: 97%

Iron(III) Contrast Agent Candidates for MRI: a Survey of the Structure–Effect Relationship in the Last 15 Years of Studies

Kuźnik

Wyskocka

2015

Eur J Inorg Chem

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“…Consistent with previous reports (17–20), the relaxation ratio R1(t)/R1(0) rapidly increased for samples containing Gd-DTPA, indicative of transmetallation (Figure 3A). (21, 22) It should be noted that components of fetal bovine serum (e.g. phosphate, carbonate, etc.)…”

Section: Resultsmentioning

confidence: 99%

Cationic gadolinium chelate for magnetic resonance imaging of cartilaginous defects

Nwe

Huang

et al. 2016

Contrast Media & Molecular

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The ability to detect meniscus defects by magnetic resonance arthrography (MRA) can be highly variable. To improve the delineation of fine tears, we synthesized a cationic gadolinium complex, (Gd-DOTA-AM4)2+, that can electrostatically interact with Glycosaminoglycans (GAGs). The complex has a longitudinal relaxivity (r1) of 4.2 mM−1s−1 and is highly stable in serum. Its efficacy in highlighting soft tissue tears was evaluated in comparison to a clinically employed contrast agent (Magnevist) using explants obtained from adult bovine menisci. In all cases, Gd-DOTA-AM4 appeared to improve the ability to detect the soft tissue defect by providing increased signal intensity along the length of the tear. Magnevist shows a strong signal near the liquid-meniscus interface, but much less contrast is observed within the defect at greater depths. This provides initial evidence that cationic contrast agents can be used to improve the diagnostic accuracy of MRA.

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“…The development of compounds with higher relaxivities could lead to contrast agents with higher sensitivity, which are detectable at lower doses and provide higher contrast at equivalent doses. The 1 relaxivity can be increased by enhancing the water-exchange rate [5,6] or by slowing down the tumbling rate of the contrast agent [7]. Dendrimers, highly branched macromolecules with a welldefined architecture, are interesting platforms for increasing the relaxivity because the increased molecular size results in a decreased molecular rotation.…”

Section: +mentioning

confidence: 99%

r1andr2Relaxivities of Dendrons Based on a OEG-DTPA Architecture: Effect of Gd³⁺Placement and Dendron Fun

Fransen

Pulido

Simón‐Gracia

et al. 2015

Journal of Nanotechnology

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Correspondence should be addressed to Fernando Albericio; albericio@irbbarcelona.org and Miriam Royo; mroyo@pcb.ub.cat In magnetic resonance imaging, contrast agents are employed to enhance the signal intensity. However, current commercial contrast agents are hindered by a low relaxivity constant. Dendrimers can be employed to create higher molecular weight contrast agents which have an increased relaxivity due to a lower molecular rotation. In this study, dendrimers containing DTPA derivatives as cores and/or branching units were used to chelate gadolinium ions. Locating the gadolinium ions inside the dendrimers results in higher relaxivity constants, possibly because the paramagnetic center is closer to the rotational axis of the macromolecule. The highest gain in relaxivity was produced by decorating the dendron surface with peptide sequences, which could be explained by the presence of more second-sphere water molecules attracted by the peptides. These findings could contribute to the development of more effective contrast agents, either by placing the paramagnetic gadolinium ion in a strategic position or through functionalization of the dendron surface.

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Gd(iii) chelates for MRI contrast agents: from high relaxivity to “smart”, from blood pool to blood–brain barrier permeable

Cited by 95 publications

References 168 publications

Iron(III) Contrast Agent Candidates for MRI: a Survey of the Structure–Effect Relationship in the Last 15 Years of Studies

Iron(III) Contrast Agent Candidates for MRI: a Survey of the Structure–Effect Relationship in the Last 15 Years of Studies

Cationic gadolinium chelate for magnetic resonance imaging of cartilaginous defects

r1andr2Relaxivities of Dendrons Based on a OEG-DTPA Architecture: Effect of Gd³⁺Placement and Dendron Fun

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Gd(iii) chelates for MRI contrast agents: from high relaxivity to “smart”, from blood pool to blood–brain barrier permeable

Cited by 95 publications

References 168 publications

Iron(III) Contrast Agent Candidates for MRI: a Survey of the Structure–Effect Relationship in the Last 15 ­Years of Studies

Iron(III) Contrast Agent Candidates for MRI: a Survey of the Structure–Effect Relationship in the Last 15 ­Years of Studies

Cationic gadolinium chelate for magnetic resonance imaging of cartilaginous defects

r1andr2Relaxivities of Dendrons Based on a OEG-DTPA Architecture: Effect of Gd3+Placement and Dendron Fun

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Iron(III) Contrast Agent Candidates for MRI: a Survey of the Structure–Effect Relationship in the Last 15 Years of Studies

Iron(III) Contrast Agent Candidates for MRI: a Survey of the Structure–Effect Relationship in the Last 15 Years of Studies

r1andr2Relaxivities of Dendrons Based on a OEG-DTPA Architecture: Effect of Gd³⁺Placement and Dendron Fun