Dual‐Frequency Calcium‐Responsive MRI Agents

Kadjane, Pascal; Platas‐Iglesias, Carlos; Boehm‐Sturm, Philipp; Truffault, Vincent; Hagberg, Gisela E.; Hoehn, Mathias; Logothetis, Nikos K.; Angelovski, Goran

doi:10.1002/chem.201400159

Cited by 48 publications

(74 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Furthermore, it is very interesting to notice that the relative abundance of the two isomers obtained from the analysis of the NMRD data (i.e., 72% SAP, 28% TSAP) matches very well to a previously reported Euanalogue of a structurally similar SCA. 21 The Ca-affinity displayed by both the liposomal SCAs was good with K d values of 10 5 −10 6 , i.e., comparable to the numbers reported in the literature for SCAs with the same motif. Moreover, the results obtained are well suitable for matching the level of changes in extracellular Ca(II) concentration in the brain.…”

Section: ■ Discussionsupporting

confidence: 83%

Innovative Design of Ca-Sensitive Paramagnetic Liposomes Results in an Unprecedented Increase in Longitudinal Relaxivity

et al. 2016

Self Cite

View full text Add to dashboard Cite

Bioresponsive MRI contrast agents sensitive to Ca(II) fluctuations may play a critical role in the development of functional molecular imaging methods to study brain physiology or abnormalities in muscle contraction. A great challenge in their chemistry is the preparation of probes capable of inducing a strong signal variation that could be detected in a robust way. To this end, the incorporation of small molecular weight bioresponsive agents into nanocarriers can improve the overall properties in a few ways: (i) the agent can be delivered into the tissue of interest, increasing the local concentration; (ii) its biokinetic properties and retention time will improve; (iii) the high molecular weight and size of the nanocarrier may cause additional changes in the MRI signal and raise the chances for their detection in functional experiments. In this work, we report the preparation of the new class of liposome-based, Ca-sensitive MRI agents. We synthesized a novel amphiphilic ligand which was incorporated into the liposome bilayer. A remarkable increase of ∼420% in longitudinal relaxivity r 1 , from 7.3 mM −1 s −1 to 38.1 mM −1 s −1 at 25°C and 21.5 MHz in the absence and presence of Ca(II), respectively, was achieved by the most active liposomal formulation. To the best of our knowledge, this is the highest change in r 1 observed for Ca-sensitive agents at physiological pH and can be explained by simultaneous Ca-triggered increase in hydration and reduction of local motion of Gd(III) complex, which can be followed at low magnetic fields.

show abstract

Section: ■ Discussionsupporting

confidence: 83%

Innovative Design of Ca-Sensitive Paramagnetic Liposomes Results in an Unprecedented Increase in Longitudinal Relaxivity

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…The coordination of this amide oxygen has been proved for similar DO3A derivatives 20. 32 Typical monohydrated, nine‐coordinate DOTA‐type chelates do not form ternary complexes at physiological pH with hydrogencarbonate or carboxylate groups 33. For dihydrated GdDO3A, both monodentate (with acetate, propionate, alanine)34 and bidentate binding was observed (with hydrogencarbonate, lactate, malonate, citrate, and carboxylate groups of proteins) 35.…”

Section: Resultsmentioning

confidence: 95%

Macrocyclic Gd³⁺ Complexes with Pendant Crown Ethers Designed for Binding Zwitterionic Neurotransmitters

Oukhatar

Meudal

Landon

et al. 2015

Chemistry A European J

Self Cite

View full text Add to dashboard Cite

A series of Gd(3+) complexes exhibiting a relaxometric response to zwitterionic amino acid neurotransmitters was synthesized. The design concept involves ditopic interactions 1) between a positively charged and coordinatively unsaturated Gd(3+) chelate and the carboxylate group of the neurotransmitters and 2) between an azacrown ether appended to the chelate and the amino group of the neurotransmitters. The chelates differ in the nature and length of the linker connecting the cyclen-type macrocycle that binds the Ln(3+) ion and the crown ether. The complexes are monohydrated, but they exhibit high proton relaxivities (up to 7.7 mM(-1) s(-1) at 60 MHz, 310 K) due to slow molecular tumbling. The formation of ternary complexes with neurotransmitters was monitored by (1) H relaxometric titrations of the Gd(3+) complexes and by luminescence measurements on the Eu(3+) and Tb(3+) analogues at pH 7.4. The remarkable relaxivity decrease (≈80 %) observed on neurotransmitter binding is related to the decrease in the hydration number, as evidenced by luminescence lifetime measurements on the Eu(3+) complexes. These complexes show affinity for amino acid neurotransmitters in the millimolar range, which can be suited to imaging concentrations of synaptically released neurotransmitters. They display good selectivity over non-amino acid neurotransmitters (acetylcholine, serotonin, and noradrenaline) and hydrogenphosphate, but selectivity over hydrogencarbonate was not achieved.

show abstract

“…Indeed, although the signal was detectable, strong paramagnetic relaxation enhancement (PRE) was reported, even for remote nuclei such as 19 F in a protease model and in a dual-frequency calcium-responsive contrast agent (CA). [2,3] On the contrary, the resonance lines of atoms in fast exchange with the bulk, such as the water molecule coordinated to the metal, are easily observed.…”

Section: Introductionmentioning

confidence: 95%

Direct Detection of ¹⁷O in [Gd(DOTA)]⁻ by NMR Spectroscopy

Fusaro

Casella

Bagno

2014

Chemistry A European J

View full text Add to dashboard Cite

The (17) O NMR spectrum of the non-coordinated carboxyl oxygen in the Gd(III) -DOTA (DOTA=tetraazacyclododecanetetraacetic acid) complex has been observed experimentally. Its line width is essentially unaffected by paramagnetic relaxation due to gadolinium, and is only affected by the quadrupole pathway. The results are supported by the relevant parameters (hyperfine and quadrupole coupling constants) calculated by relativistic DFT methods. This finding opens up new avenues for investigating the structure and reactivity of paramagnetic Gd(III) complexes used as contrast agents in magnetic resonance imaging.

show abstract

Dual‐Frequency Calcium‐Responsive MRI Agents

Cited by 48 publications

References 48 publications

Innovative Design of Ca-Sensitive Paramagnetic Liposomes Results in an Unprecedented Increase in Longitudinal Relaxivity

Innovative Design of Ca-Sensitive Paramagnetic Liposomes Results in an Unprecedented Increase in Longitudinal Relaxivity

Macrocyclic Gd³⁺ Complexes with Pendant Crown Ethers Designed for Binding Zwitterionic Neurotransmitters

Direct Detection of ¹⁷O in [Gd(DOTA)]⁻ by NMR Spectroscopy

Contact Info

Product

Resources

About

Dual‐Frequency Calcium‐Responsive MRI Agents

Cited by 48 publications

References 48 publications

Innovative Design of Ca-Sensitive Paramagnetic Liposomes Results in an Unprecedented Increase in Longitudinal Relaxivity

Innovative Design of Ca-Sensitive Paramagnetic Liposomes Results in an Unprecedented Increase in Longitudinal Relaxivity

Macrocyclic Gd3+ Complexes with Pendant Crown Ethers Designed for Binding Zwitterionic Neurotransmitters

Direct Detection of 17O in [Gd(DOTA)]− by NMR Spectroscopy

Contact Info

Product

Resources

About

Macrocyclic Gd³⁺ Complexes with Pendant Crown Ethers Designed for Binding Zwitterionic Neurotransmitters

Direct Detection of ¹⁷O in [Gd(DOTA)]⁻ by NMR Spectroscopy