Gadolinium DTPA‐Monoamide Complexes Incorporated into Mixed Micelles as Possible MRI Contrast Agents (original) (raw)
Related papers
European Journal of Inorganic Chemistry, 2003
Keywords: Imaging agents / Contrast agents / Lanthanides / Micelles / N,O ligands / NMR spectroscopy DTPA-bisamide derivatives with alkyl chains containing 14, 16 and 18 carbon atoms were synthesized and complexes of various trivalent lanthanide ions (Ln = Gd, La, Pr, Eu) were formed. Variable temperature proton NMR spectroscopy of paramagnetic praseodymium(III) and europium(III) complexes revealed that long aliphatic substituents considerably increase the energy barrier for the intramolecular rearrangement around the lanthanide ion. The gadolinium(III) complexes were incorporated into mixed micelles, and photon correlation spectroscopy showed that the mean sizes of all the micelles were within the same range. The NMRD curves of all three DTPA-bisamide-gadolinium complexes incorpor- [a]
European Journal of Inorganic Chemistry, 2000
A novel Gd-DTPA derivative with a built-in sulfonamide (SA) was synthesized as a contrast agent for MRI. The complex was designed to selectively target the enzyme carbonic anhydrase. It is shown that the longitudinal relaxation rates of aqueous solutions of Gd-DTPA-SA in the presence of carbonic anhydrase increase significantly. The binding constant is determined to be 15,000 ± 5,000 M -1 . This value ensures substantial formation of the carbonic anhydrase adduct at imaging concentrations of Gd-DTPA-SA. The complex interacts
Langmuir, 2006
In this paper, we present the development of a new potential blood pool contrast agent for magnetic resonance imaging applications (MRA/MRI) based on gadolinium complexes containing amphiphilic supramolecular aggregates. A novel amphiphilic unimer, containing the DTPAGlu chelating agent covalently bound to two C18 alkylic chains, has been synthesized. DTPAGlu is a well-known chelating agent for a wide number of ions such as the paramagnetic metal ion Gd 3+ used as contrast agent in MRA/MRI. The wide aggregation behavior of this surfactant, as free base or as gadolinium complex, has been studied and compared by means of dynamic light scattering, small-angle neutron scattering and cryogenic transmission electron microscopy techniques. Near neutral pH in both cases, the dominant aggregates are micelles.The high negative actual charge of the surfactant headgroup causes a strong headgroups repulsion, promoting the formation of large and high curvature aggregates. By decreasing pH and less markedly increasing the ionic strength, we observe a micelle-to-vesicle transition driven by a decreased electrostatic repulsion. A straightforward switch between different aggregation states can be particularly useful in the development of pHresponsive MRA/MRI contrast agents.
Radiography, 2003
Four DTPA and DOTA derivative ligands containing sulfonamide groups and their gadolinium complexes were prepared and characterized. Relaxivity studies showed that these gadolinium complexes possessed higher relaxation effectiveness than those of the corresponding ionic gadolinium complex Gd-DTPA and Gd-DOTA, respectively. In vitro cytotoxicity assay demonstrated that these gadolinium complexes have low cytotoxicity to the human liver cells (L-02). Magnetic resonance imaging (MRI) and experimental data of biodistribution in mice indicated that these gadolinium complexes containing sulfonamide groups could be used as the potential MRI contrast agents for Hepatoma (H 22 ) and Ehrlich ascites carcinoma (EAC) in mice and specific organs such as the liver and could be mostly excreted by the kidneys.
Synthesis and Evaluation of a Gd (III) Complex as T 1 -Weighted MRI Contrast Agent
https://ijshr.com/IJSHR\_Vol.4\_Issue.3\_July2019/IJSHR\_Abstract.0016.html, 2019
A hexadentate ligand, H4mum consisting of two phenyl moieties with four acetate arms was designed and synthesized. A water-soluble Gd(III) complex (1) was synthesized by reacting ligand H4mum with GdCl3·xH2O in 1:1 molar equivalent. Tb (III) congener (complex 2) of complex 1 was also synthesized and used for determining the number of coordinated water molecules present in the inner-coordination sphere of the complex by luminescence lifetime measurements. It was confirmed that the complex consisted of two directly coordinated-water molecules. At 25 °C and pH ~ 7.4 in HEPES buffer, the complex offered longitudinal relaxivity r1 value of 8.34 mM–1s–1 at a magnetic field of strength 1.41 T. However, with increasing filed strength to 14.1 T, the r1 relaxivity value slightly deceased to 7.62 mM–1s–1 at the same experimental conditions. The complex stability under physiological conditions was investigated by measuring r1 relaxivity in the presence of various physiological anions. In the presence of almost 100 equivalents (~ 50.0 mM) excess of these anions the r1 value remained almost constant, justified the complex stability under physiological conditions. Finally, phantom MR imaging under clinical scanner at 1.5 T showed positive contrast efficiency of the complex. Keywords: MRI, Contrast agents, Gadolinium (III) complex, Relaxivity, Hydration state, High field.
Polymer Chemistry, 2014
In this work, we studied the influence of the structure of macromolecular ligands on the relaxivity of gadolinium contrast agents constructed as nanoparticle systems. Macromolecular ligands were assembled as single-molecule nanoparticles in the form of either discrete core cross-linked star polymers or hyperbranched polymers. 1-(5-Amino-3-aza-2-oxypentyl)-4,7,10-tris(tert-butoxycarbonylmethyl)-1,4,7,10-tetraaza-cyclododecane (DO3A-tBu-NH 2) chelate was incorporated into different parts (arms, cores, and end-groups) of the polymeric structures using activated ester/amine nucleophilic substitutions, deprotected and complexed with Gd 3+. The relaxivity properties of the ligated Gd 3+ agents were then studied to evaluate the effect of macromolecular architecture and Gd 3+ placement on their behavior as discrete nanoparticle magnetic resonance imaging (MRI) contrast agents. The precise placement of Gd 3+ in the polymeric structures (and therefore in the nanoparticles) proved to be critical in optimizing the performance of the nanoparticles as MRI contrast agents. The relaxivity was measured to vary from 11 to 22 mM À1 s À1 , 2-5 times higher than that of a commercial DOTA-Gd contrast agent when using a magnetic field strength of 0.47 T. The relaxivity of these nanoparticles was examined at different magnetic fields from 0.47 T to 9.4 T. Finally, the residence time of the coordinated water (s M) and the rotational correlation time of the final molecule (s R) were evaluated for these different nanostructures and correlated with the polymeric architecture.
Synthesis and Physicochemical Characterisation of Gd-DTPA Derivatives as Contrast Agents for MRI
European Journal of Inorganic Chemistry, 2012
Paramagnetic magnetic resonance imaging (MRI) contrast agents are the compounds most used in clinical studies. Among these, the derivatives of Gd-DTPA (gadolinium diethylenetriaminepentaacetic acid, Magnevist ® , Bayer HealthCare) have been extensively studied. The first part of this work consists of a comparison of various derivatives of Gd-DTPA [mono-, bis-or pentaamides; C-functionalised (C 2 , C 4 , C 5 , N 6 ) or diester derivatives] according to their synthesis and to the most important parameters that regulate their efficacy. The synthesis of bis(amide)s consists of only one step and is thus easier than the synthesis of the C 4 derivatives, which needs several steps and requires a tedious purification. These last compounds are, however, more stable against transmetallation with another ion such as zinc [more than [a]
Dalton Transactions, 2014
The synthesis and characterization of two novel DTPA bisamide derivatives DTPA-BC 12 PheA and DTPA-BC 14 PheA functionalized with p-dodecylaniline and p-tetradecylaniline are described. The ligands were coordinated to Gd(III) and Eu(III), resulting in highly paramagnetic and luminescent complexes, respectively. Mixed micelles consisting of Gd/Eu-DTPA-BC 12 PheA and DTPA-BC 14 PheA with a homogeneous size distribution (33-40 nm) were prepared by the assembly of the amphiphilic complexes with phospholipid DPPC and a surfactant Tween 80®. Taking into account the sensitivity difference between magnetic resonance and optical imaging techniques, the ratios of Gd and Eu complexes (Gd/Eu) 1 : 1, 2 : 1, 3 : 1, 20 : 1 and 50 : 1 were combined in one single micelle and their optical and relaxometric properties were characterized in detail. Upon excitation at 290 nm, the micelles display characteristic red emission bands due to the 5 D 0 → 7 F J (J = 0-4) transitions of Eu(III). The number of water molecules in the first coordination sphere of Eu(III) (q Eu = 0.1-0.2) was calculated from the lifetime measurements performed in H 2 O and D 2 O solutions. Micelles composed of exclusively europium complexes display quantum yields in the range of 1.0%, decreasing with the europium concentration when going from 1 : 1 to 50 : 1 Gd/Eu contents. The ligand-to-lanthanide sensitization efficiency for micelles consisting of Eu-DTPA-BC 12 PheA and Eu-DTPA-BC 14 PheA equals 3.8% and 4.1%, respectively. The relaxivity r 1 per Gd(III) ion at 40 MHz and 310 K reaches a maximum value of 14.2 s −1 mM −1 for the Gd-DTPA-BC 12 PheA assemblies and 16.0 s −1 mM −1 for the micellar Gd-DTPA-BC 14 PheA assemblies compared to a value of 3.5 s −1 mM −1 for Gd-DTPA (Magnevist®). Theoretical fitting of the 1 H NMRD profiles results in τ R values of 4.2 to 6.6 ns. The optimal concentration ratio of Gd/Eu compounds in the micelles in order to provide the required bimodal performance has been determined to be 20 : 1. In the search for other bimodal systems, this discovery can be used as a guideline concerning the load of paramagnetic agents with respect to luminescent probes.
SYNTHESIS AND RELAXIVITY MEASUREMENTS OF NOVEL Gd(III)COMPLEX OF DOTVA AS MRA CONTRAST AGENTS
The synthesis and relaxivity of a new gadolinium(III) complex of a polyazatricarboxylate macrocycle (DOTVA) having 2-bromoisovaleric acid pendant arm is reported. The longitudinal relaxivity (r1p) of [Gd(DOTVA)(H2O)] is 6.72 mM-1 s-1 (20 MHz, 37 ± 0.1 °C, pH 7) which is higher than that of [Gd(DOTA)(H2O)]-(r1p = 4.2 mM-1 s-1 , 20 MHz)by 1.6% than the clinically approved CAs. The r2p/r1p ratio for Na[Gd(DOTVA)(H2O)] is 1.16 showing that the complex is a T1-weighted contrast agent. The complexes show pH dependent relaxivity at low and high pH values. It forms adduct with HSA and shows relaxivity enhancement. The 2-bromoisovaleric acid seems to be an excellent pendant arm functionality in making new CAs for MRI and the amide core is a versatile core molecule for the creation of polynuclear gadolinium(III) chelates and dendrimeric CAs.