Synthesis and characterization of a new water-soluble endohedral metallofullerene for MRI contrast agents

Water-soluble amino acid derivatives of gadolinium (Gd) endohedral metallofullerenes (AAD-EMFs), Gd@C₈₂O_m(OH)_n(NHCH₂CH₂COOH)_l (m ≈ 6, n ≈ 16 and l ≈ 8) are synthesized by a direct reaction of the pure endohedral metallofullerene Gd@C₈₂ with an excess of alkaline solution of β-alanine. The structure of the AAD-EMFs is characterized by FTIR, XPS and laser-desorption time-of-flight (LD-TOF) mass spectrometries. Water proton relaxivity analysis indicates that the longitudinal relaxivity R₁ (the effect on 1/T₁, 9.1 mM⁻¹ s⁻¹) of AAD-EMFs is higher than that of the commercial MRI contrast agent, Magnevist (gadolinium-diethylenetriaminepentaacetic acid, Gd-DTPA, 5.6 mM⁻¹ s⁻¹). The MRI phantom studies are performed to confirm the high efficiency of this sample as MRI contrast agents.     

A Gadolinium(III) Complex Based on the Thymine Nucleobase with Properties Suitable for Magnetic Resonance Imaging

The paramagnetic gadolinium(III) ion is used as contrast agent in magnetic resonance (MR) imaging to improve the lesion detection and characterization. It generates a signal by changing the relaxivity of protons from associated water molecules and creates a clearer physical distinction between the molecule and the surrounding tissues. New gadolinium-based contrast agents displaying larger relaxivity values and specifically targeted might provide higher resolution and better functional images. We have synthesized the gadolinium(III) complex of formula [Gd(thy)₂(H₂O)₆](ClO₄)₃·2H₂O (1) [thy = 5-methyl-1H-pyrimidine-2,4-dione or thymine], which is the first reported compound based on gadolinium and thymine nucleobase. 1 has been characterized through UV-vis, IR, SEM-EDAX, and single-crystal X-ray diffraction techniques, and its magnetic and relaxometric properties have been investigated by means of SQUID magnetometer and MR imaging phantom studies, respectively. On the basis of its high relaxivity values, this gadolinium(III) complex can be considered a suitable candidate for contrast-enhanced magnetic resonance imaging.     

Preparation,thermal stability and magnetic properties of new AgY1−xGdx(WO4)2 ceramic materials

Polycrystalline samples of α-AgY_1−xGd_x(WO₄)₂ with x=0, 0.005, 0.01, 0.025, 0.05, 0.1, 0.2, and 1 have been prepared by a solid state reaction method and the influence of Gd³⁺ substitution for Y³⁺ on microstructure, thermal and magnetic properties was investigated. The X-ray diffraction analysis showed the phases to crystallize in the monoclinic symmetry, space group C2/m. A reversible monoclinic to tetragonal phase transition occurs in AgY_1−xGd_x(WO₄)₂ and strongly depends on Gd³⁺ ion concentration. Electron paramagnetic resonance (EPR) spectra of Gd³⁺ ions showed non-monotonous dependence of interaction strength on gadolinium concentration. Magnetic measurements showed paramagnetic behavior and strong increase of magnetic moment as the yttrium content decreases.     

Gd2O3:Pr3+ nanospheres as bi-functional contrast agents for optical and magnetic resonance imaging properties

Gadolinium based luminescent materials have been researched due to their unique optical and magnetic properties with excellent chemical stability, which are useful to apply in both magnetic resonance imaging (MRI) and fluorescence imaging (FI). In this work, red emitting Gd₂O₃:Pr³⁺ nanospheres were successfully fabricated by a facile co-precipitation method. The change of reaction time influenced the size of Gd₂O₃:Pr³⁺ nanospheres and exhibited the sizes between 110 and 250?nm. The size of the Gd₂O₃:Pr³⁺ nanospheres influenced the luminescence and MR imaging signal intensity. Therefore, it can be applied for bi-functional contrast agents.     

Developing High Field MRI Contrast Agents by Tuning the Rotational Dynamics: Bisaqua GdAAZTA-based Dendrimers

Monomeric and dimeric AAZTA-based bifunctional chelators (AAZTA=6-amino-6-methylperhydro-1,4-diazepine tetraacetic acid) were attached to different generations (G0, G1 and G2) of ethylenediamine-cored PAMAM dendrimers (PAMAM=polyamidoamine) to obtain a series of six dendrimeric systems with 4 to 32 chelates at the periphery. These Gd^III-loaded dendrimers have molecular weight ranging from 3.5 to 25 kDa, thus allowing a systematic investigation on the changes in relaxivity (r₁) with the variation of the rotational dynamics following the increase in molecular size. Variable-temperature ¹⁷O NMR (on the dimeric building block Gd₂ L2 ) and ¹H Nuclear Magnetic Relaxation Dispersion measurements at different temperatures indicate that the water exchange lifetime (τ_M∼90 ns) of the two inner sphere water molecules does not represent a limiting factor to the relaxivity of the systems. The r₁ values at 1.5 T (60 MHz) and 298 K increases from 10.2 mM⁻¹ s⁻¹ for the monomer Gd L1 to 31.4 mM⁻¹ s⁻¹ for the dendrimer Gd₃₂ G2-32 (+308 %). However, the relaxivity (per Gd) does not show a linear dependence on the molecular mass, but rather the enhancement tends to attenuate markedly for larger systems. This effect has been attributed to the growing decrease in correlation between local rotational motions and global molecular tumbling.     

Thermal and structural modification in transparent and magnetic germanoborate glasses induced by Gd2O3

A series of new transparent and magnetic germanoborate glasses in the system (100-x)[60GeO₂–25B₂O₃–10Na₂O–4Al₂O₃–1PbO] – (x) Gd₂O₃, with x = 0, 1, 2, 5, 10, 15 and 20 mol%, was prepared and studied with respect to their thermal and structural changes in the presence of Gd₂O₃. Based on Differential Scanning Calorimetre (DSC) analysis, a glass with 5% of Gd₂O₃ showed a high thermal stability, which progressively decreases for samples with higher content of Gd₂O₃. By the analysis of Raman and Fourier Transform Infrared (FTIR) spectra, it was possible to identify that by increasing the amount of Gd₂O₃, a progressive depolymerization of 6-membered Ge^[IV] rings is promoted, concomitant with an increase of Ge^[IV] tetrahedra units with non-briding oxygens. The structural analysis through the local-sensitive techniques EXAFS (Extended X-ray Absorption Fine Structure) and XANES (X-ray Absorption Near Edge Structure) showed that the short-range structural modification around the elements Ge and Gd³⁺ does not change with the addition of Gd₂O₃ and the presence of germanium four-fold coordination [Ge^IV] and Gd³⁺ states, respectively. A simulation of the coordination number (N), the interatomic distance (R) of Ge–O and Gd–O bonds and the Debye-Waller factor was also carried out. The microstructure_, after crystallization, of the sample with 15 mol% of Gd₂O₃ was evaluated using optical and electron microscopes. Finally, the paramagnetic behaviour and ion probe quantification of Gd³⁺ ions were obtained based on magnetic susceptibility measurements.     

PEGylation of MnO nanoparticles via catechol–Mn chelation to improving T1‐weighted magnetic resonance imaging application

To enhance biocompatibility and physiological stability of hydrophobic MnO nanoparticles as contrast agent of T₁‐weighted magnetic resonance imaging (MRI), dopamine‐functionalized poly(ethylene glycol) (PEG) was used to coat the surface of about 5 nm MnO nanoparticles. Although hydrophilic coating might decrease longitudinal relaxivity due to inhibiting the intimate contact between manganese of nanoparticle surface and proton in water molecules, higher longitudinal relaxivity was still maintained by manipulating the PEGylation degree of MnO nanoparticles. Moreover, in vivo MRI demonstrated considerable signal enhancement in liver and kidney using PEGylated MnO nanoparticles. Interestedly, the PEGylation induced the formation of about 120 nm clusters with high stability in storing and physiological conditions, indicating passive targeting potential to tumor and prolonged circulation in blood. In addition, the cytotoxicity of PEGylated MnO nanoparticles also proved negligible. Consequently, the convenient PEGylation strategy toward MnO nanoparticles could not only realize a good “trade‐off” between hydrophilic modification and high longitudinal relaxivity but also contribute additional advantages, such as passive targeting to tumor and long blood circulation, to MRI diagnosis of tumor. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42360.     

Synthesis and magnetic relaxation properties of new Gd(III) complexes derived from DTPA-bis(amide) conjugates of arylpiperazinyl amines

Two new Gd(III) complexes 1 and 2 of the type [Gd(L)H₂O]·nH₂O were synthesized from DTPA-bis(amide) conjugates of arylpiperazinyl amines. The relaxivity (R₁) of these complexes was measured in deionized water, which revealed that complex 2 had a higher relaxivity than 1 and Omniscan®, a commercially available MRI contrast agent. The cytotoxicity studies of 1 and 2 indicated that they are non-toxic which warrant their physiological suitability as potential contrast agents for MRI. All the synthesized ligands and complexes were characterized with the aid of analytical and spectroscopic methods including elemental analysis, ¹H NMR, FT-IR, XPS and fast atom bombardment (FAB) mass spectrometry.     

Electrowinning of gadolinium metal below 1000°C. An introductory investigation

Gadolinium was recovered as dendrites by electrolysis of Gd₂O₃ dissolved in molten LiF-GdF₃ (65-35 mol%) at 850–900°C. Both inert anodes (noble metals) and graphite anode were used. With a platinum anode, anodic corrosion began at current densities (cd) of about 9 A dm^?2. Below this cd the platinum appears to be passivated, and no platinum was detected in the electrowon gadolinium. Electrolysis with graphite anode resulted in carbon contamination of about 0.14 wt% of the gadolinium metal. The electrowon metal contained 100–500 wt ppm oxygen, depending on the oxide concentration in the electrolyte.     

Structural and thermoelectric properties of GdxSr2-xCoO4 layered perovskites

Gd_xSr_2-xCoO₄-layered perovskites with varying gadolinium content (x = 0.5, 0.6, 0.7, 0.8, 0.9, 1.0) were synthesised using a conventional solid-state reaction method in air. X-ray diffraction (XRD) analysis indicated that all samples were single phase with a tetragonal I4/mmm K₂NiF₄-type structure. Rietveld refinements showed that the lattice parameters and the in-plane Co–O bond length decreased with increasing Gd³⁺ content, suggesting stronger structural distortion. The X-ray photoelectron spectroscopy (XPS) analysis indicated that cobalt ions on the surface of Gd_xSr_2-xCoO₄ had Co³⁺ and Co⁴⁺mixed valence states and many oxygen vacancies. The thermoelectric properties of Gd_xSr_2-xCoO₄ (x = 0.7, 0.8) were also investigated. The temperature dependencies of the electrical conductivity (σ) and Seebeck coefficient (S) up to 750 °C for Gd_0.7Sr_1.3CoO₄ showed maximum and minimum values at approximately 550 °C. Below 550 °C with increasing Gd³⁺ content, S increased, whereas σ and the thermal conductivity (κ) decreased, leading to an increase in the figure of merit (ZT). A maximum ZT value of 0.0039 for Gd_0.8Sr_1.2CoO₄ was obtained at 400 °C. The variations of σ, S and κ with x and temperature are discussed.     

Role of (La,Gd) co-doping on the enhanced dielectric and magnetic properties of BiFeO3 ceramics

The effect of the La³⁺ and Gd³⁺ co-doping on the structure, electric and magnetic properties of BiFeO₃ (BFO) ceramics are investigated. For the compositions (x=0 and 0≤y≤0.15) in the perovskite structured La_xGd_yBi_1−(x+y)FeO₃ system, a tiny residual phase of Bi₂Fe₄O₉ is noticed. Such a secondary phase is suppressed with the incorporation of ‘La’ content (x). The magnitude of dielectric constant (ε_r) increases progressively by increasing the ‘La’ content from x=0 to 0.15 with a remarkable decrease of dielectric loss. For x=0.15, the system La_xGd_yBi_1−(x+y)FeO₃ exhibits highest remanent magnetization (M_r) of 0.18 emu/g and coercive magnetic field (H_C) of ~1 T in the presence of external magnetic field of 9 T at 300 K. The origin of enhanced dielectric and magnetic properties of La_xGd_yBi_1−(x+y)FeO₃ and the role of doping elements, La³⁺, Gd³⁺ has been discussed.     

Microstructure and performances of Gd2O3-added corundum–mullite ceramic composites for concentrated solar power applications

Gd₂O₃ was added to increase the properties of corundum–mullite ceramic composites by enhancing the microstructural densification using coal-series kaolin and α-Al₂O₃. The effect of Gd₂O₃ addition on the microstructure and properties of ceramic composites was explored. The results showed that the formation of Gd₂O₃–Al₂O₃–SiO₂ liquid phase could improve the bending strength, hardness, and acid resistance, since such liquid phase promoted microstructural densification via a reaction between Gd₂O₃ and Al₂O₃–SiO₂ binary system in this Al₂O₃-rich and SiO₂-poor system. The precipitation of mullite and gadolinium disilicate during thermal shocks resulted in enhanced bending strength. In particular, sample AG5 (80 wt% Al₂O₃, 20 wt% coal-series kaolin, and 5 wt% additional Gd₂O₃) sintered at 1550 °C was considered as candidate for heat transmission pipeline for the optimum comprehensive performance.     

Synthesis and characterization of nanometric gadolinia powders by room temperature solid-state displacement reaction and low temperature calcination

Nanometric-sized gadolinia (Gd₂O₃) powders were obtained by applying solid-state displacement reaction at room temperature and low temperature calcination. The XRD analysis revealed that the room temperature product was gadolinium hydroxide, Gd(OH)₃. In order to induce crystallization of Gd₂O₃, the subsequent calcination at 600 ∼ 1200 °C of the room temperature reaction products was studied. Calculation of average crystallite size (D) as well as separation of the effect of crystallite size and strain of nanocrystals was performed on the basic of Williamson-Hall plots. The morphologies of powders calcined at different temperatures were followed by scanning electron microscopy. The pure cubic Gd₂O₃ phase was made at 600 °C which converted to monoclinic Gd₂O₃ phase between 1400° and 1600 °C. High-density (96% of theoretical density) ceramic pellet free of any additives was obtained after pressureless sintering at 1600 °C for 4 h in air, using calcined powder at 600 °C.     

On the local structure of Cd3+ centers in (BaGeO3)1 ? x ? y (Al2O3) x (0.45CaF2 · 0.55MgF2) y glasses

A correlation between the ¹⁵⁵Gd M?ssbauer spectra of the GdAlO₃ and Gd₃Al₅O₁₂ compounds and Gd³⁺-doped glasses in the (BaGeO₃)_{1 − x − y} (Al₂O₃) _x (0.45CaF₂ · 0.55MgF₂) _y system is revealed. The conclusion is drawn that, in the structure of the glasses under investigation, trivalent gadolinium atoms form structural units characteristic of mixed gadolinium and aluminum oxides. Original Russian Text ? S.A. Nemov, A.V. Marchenko, P.P. Seregin, 2008, published in Fizika i Khimiya Stekla.     

Size-regulated group separation of CoFe2O4 nanoparticles using centrifuge and their magnetic resonance contrast properties

Magnetic nanoparticle (MNP)-based magnetic resonance imaging (MRI) contrast agents (CAs) have been the subject of extensive research over recent decades. The particle size of MNPs varies widely and is known to influence their physicochemical and pharmacokinetic properties. There are two commonly used methods for synthesizing MNPs, organometallic and aqueous solution coprecipitation. The former has the advantage of being able to control the particle size more effectively; however, the resulting particles require a hydrophilic coating in order to be rendered water soluble. The MNPs produced using the latter method are intrinsically water soluble, but they have a relatively wide particle size distribution. Size-controlled water-soluble MNPs have great potential as MRI CAs and in cell sorting and labeling applications. In the present study, we synthesized CoFe₂O₄ MNPs using an aqueous solution coprecipitation method. The MNPs were subsequently separated into four groups depending on size, by the use of centrifugation at different speeds. The crystal shapes and size distributions of the particles in the four groups were measured and confirmed by transmission electron microscopy and dynamic light scattering. Using X-ray diffraction analysis, the MNPs were found to have an inverse spinel structure. Four MNP groups with well-selected semi-Gaussian-like diameter distributions were obtained, with measured T₂ relaxivities (r₂) at 4.7 T and room temperature in the range of 60 to 300 mM⁻¹s⁻¹, depending on the particle size. This size regulation method has great promise for applications that require homogeneous-sized MNPs made by an aqueous solution coprecipitation method. Any group of the CoFe₂O₄ MNPs could be used as initial base cores of MRI T₂ CAs, with almost unique T₂ relaxivity owing to size regulation. The methodology reported here opens up many possibilities for biosensing applications and disease diagnosis.

PACS

75.75.Fk, 78.67.Bf, 61.46.Df     

Corrosion resistance of nonstoichiometric gadolinium zirconate coatings against CaO-MgO-Al2O3-SiO2 silicate

Gadolinium zirconate is a promising next-generation thermal barrier coating material and its CaO-MgO-Al₂O₃-SiO₂ (CMAS) resistance needs to be further increased. In this study, three gadolinium zirconate coatings with different Gd/Zr ratios are successfully prepared via atmospheric plasma spray using amorphous feedstock. Their mechanical properties and corrosion resistance are investigated. The Young’s moduli and hardness of as-sprayed coatings are comparable with the gadolinium zirconate coatings reported in previous literature. Furthermore, the higher Gd content promotes the formation of the Gd-apatite and the depletion rate of CMAS corrosion. As a result, the infiltration depth of Gd_2.3Zr_1.7O_6.85 coating after 24 h annealing decreases up to 35 % compared with those of Gd_2.0Zr_2.0O_7.0 and Gd_1.8Zr_2.2O_7.1, exhibiting an enhanced long-term corrosion resistance. This work develops a viable fabrication method to produce non-stoichiometric gadolinium zirconate coatings with tailorable CMAS corrosion resistance and is expected to promote the future design of thermal barrier coatings with long service life.     

New scheelite-type Cd1−3x⌷xGd2x(MoO4)1−3x(WO4)3x ceramics – their structure,thermal and magnetic properties

Polycrystalline samples of scheelite-type Cd_1−3x⌷_xGd_2x(MoO₄)_1−3x(WO₄)_3x solid solution with limited homogeneity (0<x≤0.25) and cationic vacancies (denoted as ⌷) have successfully prepared by a high-temperature annealing of CdMoO₄/Gd₂(WO₄)₃ mixtures composed of 50.00 mol% and less of gadolinium tungstate. Initial reactants and obtained ceramic materials were characterized by XRD, simultaneous DTA–TG, and SEM techniques. A phase diagram of the pseudobinary CdMoO₄–Gd₂(WO₄)₃ system was constructed. The eutectic point corresponds to 1404±5 K and ~70.00 mol% of gadolinium tungstate in an initial CdMoO₄/Gd₂(WO₄)₃ mixture. With decreasing of Gd³⁺ content in a CdMoO₄ framework, the melting point of Cd_1−3x⌷_xGd_2x(MoO₄)_1−3x(WO₄)_3x increases from 1406 (x=0.25) to 1419 K (x=0.0833), and next decreases to 1408 K (x=0). EPR method was used to identify paramagnetic Gd³⁺ centers in Cd_1−3x⌷_xGd_2x(MoO₄)_1−3x(WO₄)_3x for different values of x parameter as well as to select biphasic samples containing both Cd_0.25⌷_0.25Gd_0.50(MoO₄)_0.25(WO₄)_0.75 and Gd₂(WO₄)₃.     

Synthesis and microstructure of Gd2O3-doped HfO2 ceramics

The effect of Gd₂O₃-doping on the crystal structure, surface morphology and chemical composition of the Gd₂O₃–HfO₂ system is reported. Gd₂O₃–HfO₂ ceramics with variable composition were prepared by varying the Gd₂O₃ composition in the range of 0–38 mol% balanced HfO₂. X-ray diffraction (XRD) analysis indicates that the Gd₂O₃ concentration influences the crystal structure of the Gd₂O₃–HfO₂ ceramics. Pure HfO₂ and Gd₂O₃ crystallize in monoclinic and body centered cubic structure, respectively. The Gd₂O₃–HfO₂ ceramics exhibit mixed monoclinic and fluorite structure when the Gd₂O₃ concentration is varied from 4 to 12 mol%. At 20 mol% of Gd₂O₃, existence of only the fluorite phase was found. Increasing the Gd₂O₃ concentration to 38 mol% results in the formation of single-phase pyrochlore Gd₂Hf₂O₇ (a = 5.258 Å).     

Gold-silver alloy nanoshells: a new candidate for nanotherapeutics and diagnostics

We have developed novel gold-silver alloy nanoshells as magnetic resonance imaging (MRI) dual T₁ (positive) and T₂ (negative) contrast agents as an alternative to typical gadolinium (Gd)-based contrast agents. Specifically, we have doped iron oxide nanoparticles with Gd ions and sequestered the ions within the core by coating the nanoparticles with an alloy of gold and silver. Thus, these nanoparticles are very innovative and have the potential to overcome toxicities related to renal clearance of contrast agents such as nephrogenic systemic fibrosis. The morphology of the attained nanoparticles was characterized by XRD which demonstrated the successful incorporation of Gd(III) ions into the structure of the magnetite, with no major alterations of the spinel structure, as well as the growth of the gold-silver alloy shells. This was supported by TEM, ICP-AES, and SEM/EDS data. The nanoshells showed a saturation magnetization of 38 emu/g because of the presence of Gd ions within the crystalline structure with r₁ and r₂ values of 0.0119 and 0.9229 mL mg^-1 s^-1, respectively (Au:Ag alloy = 1:1). T₁- and T₂-weighted images of the nanoshells showed that these agents can both increase the surrounding water proton signals in the T₁-weighted image and reduce the signal in T₂-weighted images. The as-synthesized nanoparticles exhibited strong absorption in the range of 600-800 nm, their optical properties being strongly dependent upon the thickness of the gold-silver alloy shell. Thus, these nanoshells have the potential to be utilized for tumor cell ablation because of their absorption as well as an imaging agent.     

Glycol-citrate synthesis of fine-grained oxides La2−xGdxZr2O7 and preparation of corresponding ceramics using FAST/SPS process

Single-phase superfine refractory oxides of composition La_2?xGd_xZr₂O₇ (x = 0, 0.5, 1, 1.5, 2) have been synthesized using glycol-citrate route. Dependencies of degree of dispersion and phase composition on chemical composition for such oxides were determined. Fluorite-pyrochlore transition observed during thermal treatment of these oxides was examined. It was stated that this transition occurred in the temperature range 1000–1200?°C for all formulations with exception of gadolinium zirconate Gd₂Zr₂O₇ which kept the fluorite structure even after long-term exposure (4?h) at a temperature of 1400?°С. Samples of corresponding ceramics which density amount to 95–98% of the theoretical value were obtained using FAST/SPS process. Coefficients of linear thermal expansion (CLTE) of manufactured materials were measured. It was found that CLTE values for all samples except for gadolinium zirconate were independent of temperature in the range 400–1000?°C. It was shown that Gd₂Zr₂O₇ kept the fluorite structure under conditions of FAST/SPS process at a temperature of 1600?°C.