Yttrium‐86 Is a Positron Emitting Surrogate of Gadolinium for Noninvasive Quantification of Whole‐Body Distribution of Gadolinium‐Based Contrast Agents

Gadolinium‐based contrast agents (GBCAs) are used to provide diagnostic information in clinical magnetic resonance (MR) examinations. Gadolinium (Gd) has been detected in the brain, bone and skin of patients, months and years following GBCA administration, raising concerns about long term toxicity. Despite increased scrutiny, the concentration, chemical form and fate of the retained gadolinium species remain unknown. Importantly, the whole body biodistribution and organ clearance of GBCAs is poorly understood in humans. Gadolinium lacks suitable isotopes for nuclear imaging. We demonstrate that the yttrium‐86 isotope can be used as a gadolinium surrogate. We show that Gd and their analogous Y complexes have similar properties both in solution and in vivo, and that yttrium‐86 PET can be used to track the biodistribution of GBCAs over a two‐day period.     

Gd络阴离子进入人红细胞并影响CI^—内流的机制

用质子诱导Ｘ射线发射法测定人红细胞与Ｇｄ柠檬酸和乳酸络合物温育时,胞浆,细胞膜膜脂和膜蛋白上Ｇｄ含量随时间的变化及阴离子通道抑剂对Ｇｄ进入细胞的影响。     

How the Chemical Properties of GBCAs Influence Their Safety Profiles In Vivo

The extracellular class of gadolinium-based contrast agents (GBCAs) is an essential tool for clinical diagnosis and disease management. In order to better understand the issues associated with GBCA administration and gadolinium retention and deposition in the human brain, the chemical properties of GBCAs such as relative thermodynamic and kinetic stabilities and their likelihood of forming gadolinium deposits in vivo will be reviewed. The chemical form of gadolinium causing the hyperintensity is an open question. On the basis of estimates of total gadolinium concentration present, it is highly unlikely that the intact chelate is causing the T₁ hyperintensities observed in the human brain. Although it is possible that there is a water-soluble form of gadolinium that has high relaxitvity present, our experience indicates that the insoluble gadolinium-based agents/salts could have high relaxivities on the surface of the solid due to higher water access. This review assesses the safety of GBCAs from a chemical point of view based on their thermodynamic and kinetic properties, discusses how these properties influence in vivo behavior, and highlights some clinical implications regarding the development of future imaging agents.     

Gadolinium-Based Paramagnetic Relaxation Enhancement Agent Enhances Sensitivity for NUS Multidimensional NMR-Based Metabolomics

Gadolinium is a paramagnetic relaxation enhancement (PRE) agent that accelerates the relaxation of metabolite nuclei. In this study, we noted the ability of gadolinium to improve the sensitivity of two-dimensional, non-uniform sampled NMR spectral data collected from metabolomics samples. In time-equivalent experiments, the addition of gadolinium increased the mean signal intensity measurement and the signal-to-noise ratio for metabolite resonances in both standard and plasma samples. Gadolinium led to highly linear intensity measurements that correlated with metabolite concentrations. In the presence of gadolinium, we were able to detect a broad array of metabolites with a lower limit of detection and quantification in the low micromolar range. We also observed an increase in the repeatability of intensity measurements upon the addition of gadolinium. The results of this study suggest that the addition of a gadolinium-based PRE agent to metabolite samples can improve NMR-based metabolomics.     

Gadolinium-based cancer therapeutic liposomes for chemotherapeutics and diagnostics

Gadolinium (Gd)-based cancer therapeutic liposomes can be used for chemotherapeutics and diagnostics. In this study, dual functional liposomes co-encapsulating doxorubicin (Dox) and Gd were prepared by Dox-transition metal complexation. Preparation conditions were optimized to obtain liposomes containing high concentrations of Dox and Gd. The optimized liposomes Gd250 co-encapsulated 3.6 mM of Dox and 1.9 mM of Gd. The magnetic resonance (MR) properties of Gd250 liposomes were determined using a 4.7 T MR system. Cellular uptake of Dox was determined using a flow cytometer and a confocal microscopy and that of Gd was measured using an inductively coupled plasma-atomic emission spectrometer. Although encapsulated Gd exhibited lower relaxivity than MRbester?, which is widely used for clinical diagnosis, because of limited diffusion across the liposome membrane, Gd250 liposomes showed much higher cellular uptake than that of MRbester?. In Gd250 liposomes, Gd was highly accumulated in B16F10 cells, which could provide improved contrast sensitivity for molecular imaging. Additionally, in Gd250 liposomes, Dox was highly internalized, which could enhance its cancer therapeutic effects. Consequently, we suggest that dual functional liposomes can be used as therapeutic and diagnostic carriers.     

Liver-targeting macromolecular MRI contrast agents

Macromolecular ligands with liver-targeting group (pyridoxamine, PM) PHEA-DTPA-PM and PAEA-DTPA-PM were prepared by the incorporation of different amount of diethylenetria-minepentaacetic acid monopyridoxamine group (DTPA-PM) into poly-cc, p-[N-(2-hydroxyethyl)-L-aspartamide] (PHEA) and poly-α, β-[N-(2-aminoethyl)-L-aspartamide] (PAEA). The macromolecular ligands thus obtained were further complexed with gadolinium chloride to give macromolecular MRI contrast agents with different Gd(Ⅲ) contents. These macromolecular ligands and their gadolinium complexes were characterized by 1H NMR, 1R, UV and elementary analysis. Relaxivity studies showed that these polyaspartamide gadolinium complexes possess higher relaxation effectiveness than that of the clinically used Gd-DTPA. Magnetic resonance imaging of the liver in rats and experimental data of biodistribution in mice indicate that these macromolecular MRI contrast agents containing pyridoxamine exhibit liver-targeting property.     

Metallreiche Gadoliniumhydridhalogenide

Metal-rich Gadolinium Hydride Halides Preparation, structures, and thermal behaviour of gadolinium hydride halides GdXH_n (X = Cl, Br, I; 0.7 < n < 0.9) are described. The preparation is done by heating Gd, GdH₂, and GdX₃ in sealed Ta ampoules to 900°C and 950°C. The arrangement of the heavy atoms corresponds to the 3 slab (X? Gd? Gd? X) structures of ZrCl and ZrBr. Besides these, a new stacking variant containing only 2 slabs in the identity period (2s-GdBrH_0·69 and 2s-GdIH_0·80; nomenclature of niobium dichalcogenides) is found.     

Gd(DTPA-BIN)与人血清白蛋白作用的核磁共振研究

造影剂通常为Ｇｄ３＋、Ｍｎ２＋或Ｆｅ３＋的稳定化合物．它们能改变体内水分子氢核的弛豫速率,从而提高正常与病变组织的磁共振成像（ＭａｇｎｅｔｉｃＲｅｓｏｎａｎｃｅＩｍａｇｉｎｇ,ＭＲＩ）对比度或显示体内器官的功能状态．因此,开发新优ＭＲＩ造影剂具有重要...     

Electronic and optical properties of quaternary selenides for optoelectronic applications: Insights from DFT+U-computations

The optical properties, electronic charge density, electronic structure of the new layered selenides materials, BaGdCuSe₃, CsUCuSe₃, CsZrCuSe₃, and CsGdZnSe₃ compounds have been calculated by using the full potential and linear augmented plane wave (FP-LAPW) methods as applied in the WIEN2k package, which is based on the density functional theory. The ALnMSe3 compound's structure of these was (A = Cs, Ba; Ln = Zr, Gd, U; M = Cu, Zn) is composed of (n = 1, 2) layers, which might be separated by A atoms. It is to be observed that there is strong hybridization between the s, p, and d states of Zr, Gd, and Cu atoms. Around the gadolinium atom, the charge density contours are completely circular, but the Gadolinium “Gd” atom shows an ionic nature. To calculate the refractive index, we used Kramer's Kronig correlations with the imaginary part dielectric function. The decrease in the refractive index is due to the lack of probability for direct excitation of the electrons, resulting in a loss of energy. The value of the static refractive index for all reference compounds is about 1.75–2.25, which is indication that the material used in optoelectronic devices.     

Synthese und Struktur eines zweikernigen Gadolinium(III)-Komplexes: Magnetische Austauschwechselwirkungen in alkoxyverbrückten Komplexen der Lanthanoiden

Synthesis and Structure of a Binuclear Gadolinium(III) Complex: Magnetic Exchange Interactions in Alkoxy Bridged Lanthanide Complexes The Schiff Base ligand N-salicylidene-2-(bis-(2-hydroxyethyl)amino)ethylamine (H₃sabhea) reacts with Gd(NO₃)₃ · 6 H₂O in methanol solution to yield the alkoxy bridged binuclear gadolinium(III) complex [{Gd(Hsabhea)(NO₃)}₂] · 2MeOH ( 1 ). 1 crystallizes in the monoclinic space group P2₁/c with a = 1014.8(2), b = 2059.2(4), c = 867.5(2) pm, β = 106.72(2)°, and Z = 2. The two gadolinium atoms are bridged by two alkoxide oxygen atoms with angles of 107.60(11)° at the oxygen bridgeheads and a Gd? Gd separation of 376.43(7) pm. A variable-temperature magnetic susceptibility study (2 to 280 K) of 1 revealed an antiferromagnetic coupling between the Gd(III) ions with J = ?0.198 cm^?1 (g = 1.975).     

Synthesis, characterization, and pharmacokinetic evaluation of a potential MRI contrast agent containing two paramagnetic centers with albumin binding affinity

A dinuclear gadolinium(III) complex of an amphiphilic chelating ligand, containing two diethylenetriamine-N,N,N',N',N'-pentaacetate (DTPA) moieties bridged by a bisindole derivative with three methoxy groups, has been synthesized and evaluated as a potential magnetic resonance imaging (MRI) contrast agent. Nuclear magnetic relaxation dispersion (NMRD) measurements indicate that at 20 MHz and 37 degrees C the dinuclear gadolinium(III) complex has a much higher relaxivity than [Gd(DTPA)] (6.8 vs 3.9 s(-1) mmol(-1)). The higher relaxivity of the dinuclear gadolinium(III) complex can be related to its reduced motion and larger rotational correlation time relative to [Gd(DTPA)]. In the presence of human serum albumin (HSA) the relaxivity value of the noncovalently bound dinuclear complex increases to 15.2 s(-1) per mmol of Gd3+, due to its relatively strong interaction with this protein. The fitted value of the binding constant to HSA (Ka) was found to be 10(4) M(-1). Because of its interaction with HSA, the dinuclear complex exhibits a longer elimination half-life from the plasma, and a better confinement to the vascular space compared to the commercially available [Gd(DTPA)] contrast agent. Transmetalation of the dinuclear gadolinium(III) complex by zinc(II) has been investigated. Biodistribution studies suggest that the complex is excreted by the renal pathway, and possibly by the hepatobiliary route. In vivo studies indicated that half of the normal dose of the gadolinium(III) complex enhanced the contrast in hepatic tissues around 40 % more effectively than [Gd(DTPA)]. The dinuclear gadolinium(III) complex was tested as a potential necrosis avid contrast agent (NACA), but despite the binding to HSA, it did not exhibit necrosis avidity, implying that binding to albumin is not a key parameter for necrosis-targeting properties.     

Hyaluronic Acid‐Gadolinium Complex Nanospheres as Lymphatic System‐Specific Contrast Agent for Magnetic Resonance Imaging

A novel MRI contrast agent, hyaluronic acid gadolinium complex (HA‐Gd‐DTPA) nanospheres, is prepared by the synthesis of hyaluronic acid gadolinium complexes and their assembly. The physicochemical properties are characterized, and the lymphatic targeting in vitro and in vivo are also evaluated. The results show that the HA‐Gd‐DTPA nanospheres with suitable and stable physicochemical properties could be used for in vivo lymphatic targeting studies. Furthermore, the HA‐Gd‐DTPA nanospheres have obviously higher relaxation efficiency and MRI contrast between blood vessel and lymph vessel in rabbit than that of Magnevist. Thus, the novel MRI contrast agent can be taken up selectively by lymphatic system and used as a potential MRI contrast agents in lymphatic system.     

Das erste Gadoliniumcarbidfluorid: Gd2CF2

The First Gadolinium Carbide Fluoride: Gd₂CF₂ Gd₂CF₂, the first gadolinium carbide fluoride is prepared by reaction of stoichiometric amounts of GdF₃, Gd, and C at 1250°C in sealed Ta-capsules. It is isotypic with Gd₂CBr₂ (space group P3 m1; a = 373.11(4) and c = 642.5(1) pm). The Gd atoms surround the C atoms octahedrally. Such Gd₆C octahedra are condensed via edges to form octahedral sheets, which are separated by double slabs of F^?? ions.     

Molecular Mechanics Investigation of Gadolinium(III) Complexes

Parameters for the commercially available modeling package SYBYL have been developed for Gd(3+) complexes allowing these to be studied with molecular mechanics. With these parameters and a technique termed the "coordination scan", the coordination numbers of Gd(III) based complexes can be predicted, and thus the hydration number q determined. Knowledge of q has allowed the prediction of molar relaxivities based on correlations to literature values. In addition, the calculated value DeltaE(coord) was found to successfully predict the thermodynamic stability constants for polyamino carboxylate ligands with Gd(3+). Gadolinium complexes are commonly utilized as MRI contrast agents, and thus the techniques utilized in this work should aid in the development of new contrast agents.     

Neutron conversion efficiency and gamma interference with gadolinium

Gadolinium (Gd) neutron capture plays an important role in both Gd neutron capture therapy and neutron detection. Detailed information about the low-energy electron spectrum emitted after Gd neutron capture is essential for accurately determining the dose delivery to the target and healthy tissues, as well as the effectiveness of Gd against other neutron convertors such as boron (B) and lithium (Li). Owing to issues such as charge extraction associated with the low energy of internal conversion electrons (ICEs) and high gamma interaction of Gd, its competitiveness for certain applications remains debatable. We measured the ICE spectrum of Gd, compared the energy deposition rates of neutron capture products from Gd, B, and Li compounds, and discussed issues associated with gamma sensitivity of Gd.     

One pot low temperature synthesis of graphene coupled Gd-doped ZnFe<Subscript>2</Subscript>O<Subscript>4</Subscript> nanocomposite for effective removal of antibiotic levofloxacin drug

Nanocomposites of reduced graphene oxide (rGO) coupled gadolinium doped ZnFe₂O₄ (GZFG) have been successfully one pot in-situ synthesized adopting low temperature solution process from zinc nitrate, iron nitrate, gadolinium acetate and graphene oxide with varying concentrations of gadolinium (upto 10% Gd with respect to Zn) in the precursor medium. X-ray diffraction and transmission electron microscopy studies confirm the presence of single phase cubic spinel structure of ZnFe₂O₄ that uniformly distributed over the rGO layers. With increasing Gd doping concentration in precursor medium, the average crystallite size of ZnFe₂O₄ diminishes gradually from ~11 to ~5.5?nm. Raman and X-ray photoelectron spectral analyses confirm an existence of interaction between rGO and ZnFe₂O₄ in GZFG samples. Using antibiotic levofloxacin in water, the drug removal capacity (DRC) of GZFG has been performed by optimization of parameters such as gadolinium doping concentration in precursor medium, solution pH, etc. However, the gadolinium doping leads to an improvement in DRC of the nanocomposite and the 5% Gd doped sample shows about 86% DRC at the optimized condition. This simple strategy can be utilized in the synthesis of rGO coupled Gd doped other metal oxide nanocomposites for DRC application.

Open image in new window

     

XMCD for monitoring exchange interactions. The role of the Gd 4f and 5d orbitals in metal-nitronyl nitroxide magnetic chains

We report here the X-ray magnetic circular dichroism (XMCD) study at the Gd M(4,5)- and L(2,3)-edges of two linear magnetic chains involving Gd(III) cations bridged by nitronyl nitroxide radicals. This spectroscopy directly probes the magnetic moments of the 4f and 5d orbitals of the gadolinium ions. We compare macroscopic magnetic measurements and local XMCD signals. The M(4,5)-edges results are in agreement with the J values extracted from the fits of the SQUID magnetic measurements. The L(2,3)-edges signals show that the electronic density in the Gd 5d orbitals depends on the neighbors of the gadolinium cations. Nevertheless, the 5d orbitals do not seem to play any role in the superexchange pathway between radicals through the metal ion proposed to explain the particular magnetic exchange interactions between the radicals in these chains.     

Synthesis of novel texaphyrins containing lanthanides and boron

Texaphyrin macrocycles that contain gadolinium or lutetium, such as motexafin gadolinium and motexafin lutetium, are versatile anticancer therapeutics and diagnostics. Gadolinium texaphyrins substituted with carborane clusters could also find application in combined gadolinium and boron neutron capture therapy (GdB-NCT). The synthesis and characterization of novel texaphyrins containing gadolinium or lutetium in the pentaaza core and two carborane clusters bound to opposite pyrrol units of the macrocycle are described.     

Coordinatively saturated gadolinium compounds for design of liquid organic scintillators

Coordinatively saturated gadolinium compounds based on gadolinium 3,5,5-trimethylhexanoate Gd(TMHA)₃ with additives of trioctylphosphine oxide and free 3,5,5-trimethylhexanoic acid were synthesized and studied to design Gd-containing scintillators for antineutrino detection. The obtained complexes were used for preparing 0.1% solutions of Gd in linear alkylbenzene and optical properties of the solutions were measured.     

Adsorption of Trivalent Cations on Silica

The temperature effect on the magnitude of adsorption was used to explain the mechanism of adsorption of gadolinium on silica at very low concentrations. Standard enthalpy of adsorption of gadolinium equals 36 kJ mol-1 for a total Gd concentration of 2 x 10(-8) mol dm-3 and 67 kJ mol-1 for 2 x 10(-5) mol dm-3. This result confirms the hypothesis that the Gd adsorption at low initial concentration is governed by formation of strong ternary surface complexes involving anionic impurities. Copyright 1999 Academic Press.