Critical Questions Regarding Gadolinium Deposition in the Brain and Body After Injections of the Gadolinium-Based Contrast Agents, Safety, and Clinical Recommendations in Consideration of the EMA's Pharmacovigilance and Risk Assessment Committee Recommendation for Suspension of the Marketing Authorizations for 4 Linear Agents.

PubMed

Runge, Val M

2017-06-01

For magnetic resonance, the established class of intravenous contrast media is the gadolinium-based contrast agents. In the 3 decades since initial approval, these have proven in general to be very safe for human administration. However, in 2006, a devastating late adverse reaction to administration of the less stable gadolinium-based contrast agents was identified, nephrogenic systemic fibrosis. The result of actions taken by the European Medicines Agency and the US Food and Drug Administration, stratifying the agents by risk and contraindicating specific agents in severe renal dysfunction, has led to no new cases being identified in North America or Europe. Subsequently, in 2014, long-term deposition in the brain of gadolinium was first shown, after administration of 2 nonionic linear chelates, gadodiamide, and gadopentetate dimeglumine. This has led to an intense focus on the question of in vivo distribution, possible dechelation, and subsequent deposition of gadolinium, together with substantial clarification of the phenomenon as well as stratification of the agents on this basis. This review focuses on 8 critical questions regarding gadolinium deposition in the brain and body, with the answers and discussion therein important for future regulatory decisions and clinical practice. It is now clear that dechelation of gadolinium occurs in vivo with the linear agents and is responsible for this phenomenon, with key experts in the field recommending, except where there is no suitable alternative, a shift in clinical practice from the linear to macrocyclic agents. In addition, on March 10, 2017, the Pharmacovigilance and Risk Assessment Committee of the European Medicines Agency recommended suspension of the marketing authorization for 4 linear gadolinium contrast agents-specifically Omniscan, Optimark, Magnevist, and MultiHance (gadodiamide, gadoversetamide, gadopentetate dimeglumine, and gadobenate dimeglumine)-for intravenous injection. Cited in the report was convincing evidence of gadolinium deposition in the brain months after injection of these linear agents. Primovist/Eovist (gadoxetic acid disodium) will remain available, being used at a lower dose for liver imaging, because it meets an important diagnostic need. In addition, a formulation of Magnevist for intra-articular injection will remain available because of its very low gadolinium concentration.

Biodegradable gadolinium-chelated cationic poly(urethane amide) copolymers for gene transfection and magnetic resonance imaging.

PubMed

Gao, Xiaolong; Wang, Gangmin; Shi, Ting; Shao, Zhihong; Zhao, Peng; Shi, Donglu; Ren, Jie; Lin, Chao; Wang, Peijun

2016-08-01

Theranostic nano-polyplexes containing gene and imaging agents hold a great promise for tumor diagnosis and therapy. In this work, we develop a group of new gadolinium (Gd)-chelated cationic poly(urethane amide)s for gene delivery and T1-weighted magnetic resonance (MR) imaging. Cationic poly(urethane amide)s (denoted as CPUAs) having multiple disulfide bonds, urethane and amide linkages were synthesized by stepwise polycondensation reaction between 1,4-bis(3-aminopropyl)piperazine and a mixture of di(4-nitrophenyl)-2, 2'-dithiodiethanocarbonate (DTDE-PNC) and diethylenetriaminepentaacetic acid (DTPA) dianhydride at varied molar ratios. Then, Gd-chelated CPUAs (denoted as GdCPUAs) were produced by chelating Gd(III) ions with DTPA residues of CPUAs. These GdCPUAs could condense gene into nanosized and positively-charged polyplexes in a physiological condition and, however, liberated gene in an intracellular reductive environment. In vitro transfection experiments revealed that the GdCPUA at a DTDE-PNC/DTPA residue molar ratio of 85/15 induced the highest transfection efficiency in different cancer cells. This efficiency was higher than that yielded with 25kDa branched polyethylenimine as a positive control. GdCPUAs and their polyplexes exhibited low cytotoxicity when an optimal transfection activity was detected. Moreover, GdCPUAs may serve as contrast agents for T1-weighted magnetic resonance imaging. The results of this work indicate that biodegradable Gd-chelated cationic poly(urethane amide) copolymers have high potential for tumor theranostics. Copyright © 2016 Elsevier B.V. All rights reserved.

Simple method for quantification of gadolinium magnetic resonance imaging contrast agents using ESR spectroscopy.

PubMed

Takeshita, Keizo; Kinoshita, Shota; Okazaki, Shoko

2012-01-01

To develop an estimation method of gadolinium magnetic resonance imaging (MRI) contrast agents, the effect of concentration of Gd compounds on the ESR spectrum of nitroxyl radical was examined. A solution of either 4-oxo-2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPONE) or 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPOL) was mixed with a solution of Gd compound and the ESR spectrum was recorded. Increased concentration of gadolinium-diethylenetriamine pentaacetic acid chelate (Gd-DTPA), an MRI contrast agent, increased the peak-to-peak line widths of ESR spectra of the nitroxyl radicals, in accordance with a decrease of their signal heights. A linear relationship was observed between concentration of Gd-DTPA and line width of ESR signal, up to approximately 50 mmol/L Gd-DTPA, with a high correlation coefficient. Response of TEMPONE was 1.4-times higher than that of TEMPOL as evaluated from the slopes of the lines. The response was slightly different among Gd compounds; the slopes of calibration curves for acua[N,N-bis[2-[(carboxymethyl)[(methylcarbamoyl)methyl]amino]ethyl]glycinato(3-)]gadolinium hydrate (Gd-DTPA-BMA) (6.22 μT·L/mmol) and gadolinium-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid chelate (Gd-DOTA) (6.62 μT·L/mmol) were steeper than the slope for Gd-DTPA (5.45 μT·L/mmol), whereas the slope for gadolinium chloride (4.94 μT·L/mmol) was less steep than that for Gd-DTPA. This method is simple to apply. The results indicate that this method is useful for rough estimation of the concentration of Gd contrast agents if calibration is carried out with each standard compound. It was also found that the plot of the reciprocal square root of signal height against concentrations of contrast agents could be useful for the estimation if a constant volume of sample solution is taken and measured at the same position in the ESR cavity every time.

Low-Molecular-Weight Iron Chelates May Be an Alternative to Gadolinium-based Contrast Agents for T1-weighted Contrast-enhanced MR Imaging.

PubMed

Boehm-Sturm, Philipp; Haeckel, Akvile; Hauptmann, Ralf; Mueller, Susanne; Kuhl, Christiane K; Schellenberger, Eyk A

2018-02-01

Purpose To synthesize two low-molecular-weight iron chelates and compare their T1 contrast effects with those of a commercial gadolinium-based contrast agent for their applicability in dynamic contrast material-enhanced (DCE) magnetic resonance (MR) imaging. Materials and Methods The animal experiments were approved by the local ethics committee. Two previously described iron (Fe) chelates of pentetic acid (Fe-DTPA) and of trans-cyclohexane diamine tetraacetic acid (Fe-tCDTA) were synthesized with stability constants several orders of magnitude higher than those of gadolinium-based contrast agents. The T1 contrast effects of the two chelates were compared with those of gadopentetate dimeglumine in blood serum phantoms at 1.5 T, 3 T, and 7 T. For in vivo studies, a human breast cancer cell line (MDA-231) was implanted in five mice per group. The dynamic contrast effects of the chelates were compared by performing DCE MR imaging with intravenous application of Fe-DTPA or Fe-tCDTA on day 1 and DCE MR imaging in the same tumors with gadopentetate dimeglumine on day 2. Quantitative DCE maps were generated with software and were compared by means of a one-tailed Pearson correlation test. Results Relaxivities in serum (0.94 T at room temperature) of Fe-tCDTA (r1 = 2.2 mmol -1 · sec -1 , r2 = 2.5 mmol -1 · sec -1 ) and Fe-DTPA (r1 = 0.9 mmol -1 · sec -1 , r2 = 0.9 mmol -1 · sec -1 ) were approximately twofold and fivefold lower, respectively, compared with those of gadopentetate dimeglumine (r1 = 4.1 mmol -1 · sec -1 , r2 = 4.8 mmol -1 · sec -1 ). Used at moderately higher concentrations, however, iron chelates generated similar contrast effects at T1-weighted MR imaging in vitro in serum, in vivo in blood, and for DCE MR imaging of breast cancer xenografts. The volume transfer constant values for Fe-DTPA and Fe-tCDTA in the same tumors correlated well with those observed for gadopentetate dimeglumine (Fe-tCDTA Pearson R, 0.99; P = .0003; Fe-DTPA Pearson R, 0.97; P = .003). Conclusion Iron-based contrast agents are promising as alternatives for contrast enhancement at T1-weighted MR imaging and have the potential to contribute to the safety of MR imaging. © RSNA, 2017 Online supplemental material is available for this article.

Revisiting the Pharmacokinetic Profiles of Gadolinium-Based Contrast Agents: Differences in Long-Term Biodistribution and Excretion.

PubMed

Lancelot, Eric

2016-11-01

Gadolinium-based contrast agents (GBCAs) have been used for years for magnetic resonance imaging examinations. Because of their rapid blood clearance, they were considered as very safe products until some of them were shown to induce nephrogenic systemic fibrosis in patients with renal failure and hypersignals on T1-weighted unenhanced brain scans of patients with normal renal function. To date, these adverse effects have been related almost exclusively to the use of low-stability linear agents, which are more prone to release free gadolinium. The aim of the present meta-analysis was to ascertain the existence of a deep compartment for gadolinium storage in the body and to assess whether all the GBCAs present the same toxicokinetic profile. Applying a systematic literature search methodology, all clinical and preclinical studies reporting time-dependent plasma concentrations and renal excretion data of gadolinium were identified and analyzed. Since the individual data were not available, the analysis focused on the average values per groups of subjects or animals, which had received a given GBCA at a given dose. The rate constants of the distribution phase (α), rapid elimination phase (β), and residual excretion phase (γ) of gadolinium were determined in each group from the plasma concentration (Cp) time curves and the relative urinary excretion rate (rER) time curves, taking the 2-hour time point as a reference. Moreover, as bone may represent a reservoir for long-term gadolinium accumulation and slow release into the blood stream, the time curves of the relative concentration in the bone (rCB) of Gd-labeled GBCAs in mice or rats were analyzed taking day 1 concentrations as a reference. The ratio of gadolinium concentrations in the bone marrow (CBM) as compared with the bone (CB) was also calculated. The relative urinary excretion rate (rER) plots revealed a prolonged residual excretion phase of gadolinium in healthy volunteers, consistent with the existence of a deep compartment of distribution for the GBCAs. The rate constant γ of gadoterate meglumine (0.107 hour) is 5 times higher than that of the linear agents (0.020 ± 0.008 hour), indicating a much faster blood clearance for the macrocyclic GBCA. Similar results were obtained in the preclinical studies. A strong correlation was shown between the γ values of the different products and their respective thermodynamic stability constants (Ktherm). Greater clearance rates of Gd from murine bone were also found after gadoterate meglumine or gadoteridol injection (0.131-0.184 day) than after administration of the linear agents (0.004-0.067 day). The concentrations of Gd in the bone marrow (CBM) from animals exposed to either gadoterate meglumine or gadodiamide are higher than those in the bone (CB) for at least 24 hours. Moreover, the ratio of concentrations (CBM/CB) at 4 hours is significantly lower with the former agent than the latter (1.9 vs 6.5, respectively). Using a nonconventional pharmacokinetic approach, we showed that gadoterate meglumine undergoes a much faster residual excretion from the body than the linear GBCAs, a process that seems related to the thermodynamic stability of the different chelates. Gadolinium dissociation occurs in vivo for some linear chelates, a mechanism that may explain their long-term retention and slow release from bone. Potential consequences in terms of bone toxicity warrant further investigations.

Graphene Oxide and Gadolinium-Chelate Functionalized Poly(lactic acid) Nanocapsules Encapsulating Perfluorooctylbromide for Ultrasound/Magnetic Resonance Bimodal Imaging Guided Photothermal Ablation of Cancer.

PubMed

Li, Zhenglin; Ke, Hengte; Wang, Jinrui; Miao, Zhaohua; Yue, Xiuli

2016-03-01

This paper successfully fabricated a novel multifunctional theranostic agent (PFOB@PLA/GO/Gd-DTPA NCs) by loading perfluorooctylbromide (PFOB) into poly(lactic acid) (PLA) nanocapsules (NCs) followed by surface functionalization with graphene oxide (GO) and gadolinium-chelate (Gd-DTPA). It was found that the resulting nanoagent could serve as a contrast agent simultaneously to enhance ultrasound (US) and magnetic resonance imaging (MRI). Benefiting from the strong absorption in the near infrared (NIR) region, the nanocapsules could efficiently kill cancer cells under NIR laser irradiation. Thus, such a single theranostic agent with the combination of realtime US imaging and high-resolution MR imaging could achieve great therapeutic effectiveness without systemic damage to the body. In addition, the cytotoxicity assay on HUVEC cells revealed a good biocompatibility of PFOB@PLA/GO/Gd-DTPA NCs, showing that the versatile nanocapsule system may hold great potential as an effective nanoplatform for contrast enhanced imaging guided photothermal therapy.

Modular Carbon and Gold Nanoparticles for High Field MR Imaging and Theranostics

NASA Astrophysics Data System (ADS)

Rammohan, Nikhil

The ability to track labeled cancer cells in vivo would allow researchers to study their distribution, growth and metastatic potential within the intact organism. Magnetic Resonance (MR) imaging is invaluable for tracking cancer cells in vivo as it benefits from high spatial resolution and absence of ionizing radiation. However, many MR contrast agents (CAs) required to label cells either do not significantly accumulate in cells or are not biologically compatible for translational studies. Accordingly, we have developed carbon- and gold-nanoparticles coupled to gadolinium(III) [Gd(III)] chelates for T1-weighted MR imaging that demonstrated remarkable properties for cell tracking in vitro and in vivo.. We created nanodiamond-Gd(III) aggregates (NDG) by peptide coupling Gd(III) chelates to aminated nanodiamonds. NDG had high relaxivity independent of field strength (unprecedented for Gd(III)-nanoparticle conjugates), and demonstrated a 300-fold increase in cellular delivery of Gd(III) compared to clinical Gd(III) chelates. Further, we were able to monitor the tumor growth of NDG-labeled flank tumors by T1-weighted MRI for 26 days in vivo, longer than reported for other MR CAs or nuclear agents. Further, theranostic nanodiamond-gadolinium(III)-doxorubicin (ND-Gd-Dox) aggregates were generated by conjugating doxorubicin (ND-Gd-Dox), which enabled efficient cancer chemotherapy in breast cancer cells. Further, we synthesized Gd(III)-gold nanoconjugates (Gd AuNPs) with varied chelate structure and nanoparticle-chelate linker length. Significantly enhanced cell labeling was demonstrated compared to previous gadolinium-gold-DNA nanoconstructs. Differences in Gd(III) loading, surface packing and cell uptake were observed between four different Gd AuNP formulations suggesting that linker length and surface charge play an important role in cell labeling. The best performing Gd AuNPs afforded 23.6 +/- 3.6 fmol of Gd(III) per cell at an incubation concentration of 27.5 microM. This efficiency of Gd(III) payload delivery (Gd(III)/cell normalized to dose) exceeds that of previously Gd(III)-Au conjugates and most other Gd(III)-nanoparticle formulations. Finally, Gd AuNPs were the first MR CAs of any type to effectively image the pancreas in vivo. . In summary, both Gd AuNPs and NDG support future MR-mediated cell tracking and theranostic applications in whole-animal models.

A polymeric fastener can easily functionalize liposome surfaces with gadolinium for enhanced magnetic resonance imaging.

PubMed

Smith, Cartney E; Shkumatov, Artem; Withers, Sarah G; Yang, Binxia; Glockner, James F; Misra, Sanjay; Roy, Edward J; Wong, Chun-Ho; Zimmerman, Steven C; Kong, Hyunjoon

2013-11-26

Common methods of loading magnetic resonance imaging (MRI) contrast agents into nanoparticles often suffer from challenges related to particle formation, complex chemical modification/purification steps, and reduced contrast efficiency. This study presents a simple, yet advanced process to address these issues by loading gadolinium, an MRI contrast agent, exclusively on a liposome surface using a polymeric fastener. The fastener, so named for its ability to physically link the two functional components together, consisted of chitosan substituted with diethylenetriaminepentaacetic acid (DTPA) to chelate gadolinium, as well as octadecyl chains to stabilize the modified chitosan on the liposome surface. The assembly strategy, mimicking the mechanisms by which viruses and proteins naturally anchor to a cell, provided greater T1 relaxivity than liposomes loaded with gadolinium in both the interior and outer leaflet. Gadolinium-coated liposomes were ultimately evaluated in vivo using murine ischemia models to highlight the diagnostic capability of the system. Taken together, this process decouples particle assembly and functionalization and, therefore, has considerable potential to enhance imaging quality while alleviating many of the difficulties associated with multifunctional particle fabrication.

A Polymeric Fastener can Easily Functionalize Liposome Surfaces with Gadolinium for Enhanced Magnetic Resonance Imaging

PubMed Central

Smith, Cartney E.; Shkumatov, Artem; Withers, Sarah G.; Glockner, James F.; Misra, Sanjay; Roy, Edward J.; Wong, Chun-Ho; Zimmerman, Steven C.; Kong, Hyunjoon

2013-01-01

Common methods of loading magnetic resonance imaging (MRI) contrast agents into nanoparticles often suffer from challenges related to particle formation, complex chemical modification/purification steps, and reduced contrast efficiency. This study presents a simple, yet advanced process to address these issues by loading gadolinium, an MRI contrast agent, exclusively on a liposome surface using a polymeric fastener. The fastener, so named for its ability to physically link the two functional components together, consisted of chitosan substituted with diethylenetriaminepentaacetic acid (DTPA) to chelate gadolinium, as well as octadecyl chains to stabilize the modified chitosan on the liposome surface. The assembly strategy, mimicking the mechanisms by which viruses and proteins naturally anchor to a cell, provided greater T1 relaxivity than liposomes loaded with gadolinium in both the interior and outer leaflet. Gadolinium-coated liposomes were ultimately evaluated in vivo using murine ischemia models to highlight the diagnostic capability of the system. Taken together, this process decouples particle assembly and functionalization, and therefore has considerable potential to enhance imaging quality while alleviating many of the difficulties associated with multifunctional particle fabrication. PMID:24083377

New Clathrin-Based Nanoplatforms for Magnetic Resonance Imaging

PubMed Central

Vitaliano, Gordana D.; Vitaliano, Franco; Rios, Jose D.; Renshaw, Perry F.; Teicher, Martin H.

2012-01-01

Background Magnetic Resonance Imaging (MRI) has high spatial resolution, but low sensitivity for visualization of molecular targets in the central nervous system (CNS). Our goal was to develop a new MRI method with the potential for non-invasive molecular brain imaging. We herein introduce new bio-nanotechnology approaches for designing CNS contrast media based on the ubiquitous clathrin cell protein. Methodology/Principal Findings The first approach utilizes three-legged clathrin triskelia modified to carry 81 gadolinium chelates. The second approach uses clathrin cages self-assembled from triskelia and designed to carry 432 gadolinium chelates. Clathrin triskelia and cages were characterized by size, structure, protein concentration, and chelate and gadolinium contents. Relaxivity was evaluated at 0.47 T. A series of studies were conducted to ascertain whether fluorescent-tagged clathrin nanoplatforms could cross the blood brain barriers (BBB) unaided following intranasal, intravenous, and intraperitoneal routes of administration. Clathrin nanoparticles can be constituted as triskelia (18.5 nm in size), and as cages assembled from them (55 nm). The mean chelate: clathrin heavy chain molar ratio was 27.04±4.8: 1 for triskelia, and 4.2±1.04: 1 for cages. Triskelia had ionic relaxivity of 16 mM−1s−1, and molecular relaxivity of 1,166 mM−1s−1, while cages had ionic relaxivity of 81 mM−1s−1 and molecular relaxivity of 31,512 mM−1s−1. Thus, cages exhibited 20 times higher ionic relaxivity and 8,000-fold greater molecular relaxivity than gadopentetate dimeglumine. Clathrin nanoplatforms modified with fluorescent tags were able to cross or bypass the BBB without enhancements following intravenous, intraperitoneal and intranasal administration in rats. Conclusions/Significance Use of clathrin triskelia and cages as carriers of CNS contrast media represents a new approach. This new biocompatible protein-based nanotechnology demonstrated suitable physicochemical properties to warrant further in vivo imaging and drug delivery studies. Significantly, both nanotransporters crossed and/or bypassed the BBB without enhancers. Thus, clathrin nanoplatforms could be an appealing alternative to existing CNS bio-nanotechnologies. PMID:22563470

Thermodynamic stability and kinetic inertness of a Gd-DTPA bisamide complex grafted onto gold nanoparticles.

PubMed

Mogilireddy, Vijetha; Déchamps-Olivier, Isabelle; Alric, Christophe; Laurent, Gautier; Laurent, Sophie; Vander Elst, Luce; Muller, Robert; Bazzi, Rana; Roux, Stéphane; Tillement, Olivier; Chuburu, Françoise

2015-01-01

Gold nanoparticles coated by gadolinium (III) chelates (Au@DTDTPA) where DTDTPA is a dithiolated bisamide derivative of diethylenetriamine-N,N,N',N'',N''-pentaacetic acid (DTPA), constituted contrast agents for both X-ray computed tomography and magnetic resonance imaging. In an MRI context, highly stable Gd(3+) complexes are needed for in vivo applications. Thus, knowledge of the thermodynamic stability and kinetic inertness of these chelates, when grafted onto gold nanoparticles, is crucial since bisamide DTPA chelates are usually less suited for Gd(3+) coordination than DTPA. Therefore, these parameters were evaluated by means of potentiometric titrations and relaxivity measurements. The results showed that, when the chelates were grafted onto the nanoparticle, not only their thermodynamic stability but also their kinetic inertness were improved. These positive effects were correlated to the chelate packing at the nanoparticle surface that stabilized the corresponding Gd(3+) complexes and greatly enhanced their kinetic inertness. Copyright © 2014 John Wiley & Sons, Ltd.

A neutral polydisulfide containing Gd(III) DOTA monoamide as a redox-sensitive biodegradable macromolecular MRI contrast agent.

PubMed

Ye, Zhen; Zhou, Zhuxian; Ayat, Nadia; Wu, Xueming; Jin, Erlei; Shi, Xiaoyue; Lu, Zheng-Rong

2016-01-01

This work aims to develop safe and effective gadolinium (III)-based biodegradable macromolecular MRI contrast agents for blood pool and cancer imaging. A neutral polydisulfide containing macrocyclic Gd-DOTA monoamide (GOLS) was synthesized and characterized. In addition to studying the in vitro degradation of GOLS, its kinetic stability was also investigated in an in vivo model. The efficacy of GOLS for contrast-enhanced MRI was examined with female BALB/c mice bearing 4T1 breast cancer xenografts. The pharmacokinetics, biodistribution, and metabolism of GOLS were also determined in mice. GOLS has an apparent molecular weight of 23.0 kDa with T1 relaxivities of 7.20 mM(-1) s(-1) per Gd at 1.5 T, and 6.62 mM(-1) s(-1) at 7.0 T. GOLS had high kinetic inertness against transmetallation with Zn(2+) ions, and its polymer backbone was readily cleaved by L-cysteine. The agent showed improved efficacy for blood pool and tumor MR imaging. The structural effect on biodistribution and in vivo chelation stability was assessed by comparing GOLS with Gd(HP-DO3A), a negatively charged polydisulfide containing Gd-DOTA monoamide GODC, and a polydisulfide containing Gd-DTPA-bisamide (GDCC). GOLS showed high in vivo chelation stability and minimal tissue deposition of gadolinium. The biodegradable macromolecular contrast agent GOLS is a promising polymeric contrast agent for clinical MR cardiovascular imaging and cancer imaging. Copyright © 2015 John Wiley & Sons, Ltd.

Chiral DOTA chelators as an improved platform for biomedical imaging and therapy applications.

PubMed

Dai, Lixiong; Jones, Chloe M; Chan, Wesley Ting Kwok; Pham, Tiffany A; Ling, Xiaoxi; Gale, Eric M; Rotile, Nicholas J; Tai, William Chi-Shing; Anderson, Carolyn J; Caravan, Peter; Law, Ga-Lai

2018-02-27

Despite established clinical utilisation, there is an increasing need for safer, more inert gadolinium-based contrast agents, and for chelators that react rapidly with radiometals. Here we report the syntheses of a series of chiral DOTA chelators and their corresponding metal complexes and reveal properties that transcend the parent DOTA compound. We incorporated symmetrical chiral substituents around the tetraaza ring, imparting enhanced rigidity to the DOTA cavity, enabling control over the range of stereoisomers of the lanthanide complexes. The Gd chiral DOTA complexes are shown to be orders of magnitude more inert to Gd release than [GdDOTA] - . These compounds also exhibit very-fast water exchange rates in an optimal range for high field imaging. Radiolabeling studies with (Cu-64/Lu-177) also demonstrate faster labelling properties. These chiral DOTA chelators are alternative general platforms for the development of stable, high relaxivity contrast agents, and for radiometal complexes used for imaging and/or therapy.

High Relaxivity Gadolinium Hydroxypyridonate-Viral Capsid Conjugates: Nano-sized MRI Contrast Agents

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meux, Susan C.; Datta, Ankona; Hooker, Jacob M.

2007-08-29

High relaxivity macromolecular contrast agents based on the conjugation of gadolinium chelates to the interior and exterior surfaces of MS2 viral capsids are assessed. The proton nuclear magnetic relaxation dispersion (NMRD) profiles of the conjugates show up to a five-fold increase in relaxivity, leading to a peak relaxivity (per Gd{sup 3+} ion) of 41.6 mM{sup -1}s{sup -1} at 30 MHz for the internally modified capsids. Modification of the exterior was achieved through conjugation to flexible lysines, while internal modification was accomplished by conjugation to relatively rigid tyrosines. Higher relaxivities were obtained for the internally modified capsids, showing that (1) theremore » is facile diffusion of water to the interior of capsids and (2) the rigidity of the linker attaching the complex to the macromolecule is important for obtaining high relaxivity enhancements. The viral capsid conjugated gadolinium hydroxypyridonate complexes appear to possess two inner-sphere water molecules (q = 2) and the NMRD fittings highlight the differences in the local motion for the internal ({tau}{sub RI} = 440 ps) and external ({tau}{sub RI} = 310 ps) conjugates. These results indicate that there are significant advantages of using the internal surface of the capsids for contrast agent attachment, leaving the exterior surface available for the installation of tissue targeting groups.« less

Gadolinium released by the linear gadolinium-based contrast-agent Gd-DTPA decreases the activity of human epithelial Na+ channels (ENaCs).

PubMed

Knoepp, Fenja; Bettmer, Joerg; Fronius, Martin

2017-05-01

Gadolinium-based-contrast-agents (GBCAs) are used for magnetic-resonance-imaging and associated with renal and cardiovascular adverse reactions caused by released Gd 3+ ions. Gd 3+ is also a modulator of mechano-gated ion channels, including the epithelial Na + channel (ENaC) that is expressed in kidney epithelium and the vasculature. ENaC is important for salt-/water homeostasis and blood pressure regulation and a likely target of released Gd 3+ from GBCAs causing the above-mentioned adverse reactions. Therefore this study examined the effect of Gd 3+ and GBCAs on ENaC's activity. Human αβγENaC was expressed in Xenopus laevis oocytes and exposed to Gd 3+ , linear (Gd-DTPA, Magnevist) or cyclic (Dotarem) GBCAs. Transmembrane ion-currents (I M ) were recorded by the two-electrode-voltage-clamp technique and Gd 3+ -release by Gd-DTPA was confirmed by inductively coupled plasma-mass spectrometry. Gd 3+ exerts biphasic effects on ENaC's activity: ≤0.3mmol/l decreased I M which was preventable by DEPC (modifies histidines). Strikingly Gd 3+ ≥0.4mmol/l increased I M and this effect was prevented by cysteine-modifying MTSEA. Linear Gd-DTPA and Magnevist mimicked the effect of ≤0.3mmol/l Gd 3+ , whereas the chelator DTPA showed no effect. Gd 3+ and Gd-DTPA increased the IC 50 for amiloride, but did not affect ENaC's self-inhibition. Interestingly, cyclic Gd-DOTA (Dotarem) increased I M to a similar extent as its chelator DOTA, suggesting that the chelator rather than released Gd 3+ is responsible for this effect. These results confirm Gd 3+ -release from linear Gd-DTPA and indicate that the released Gd 3+ amount is sufficient to interfere with ENaC's activity to provide putative explanations for GBCA-related adverse effects. Copyright © 2017 Elsevier B.V. All rights reserved.

Chelating DTPA amphiphiles: ion-tunable self-assembly structures and gadolinium complexes.

PubMed

Moghaddam, Minoo J; de Campo, Liliana; Kirby, Nigel; Drummond, Calum J

2012-10-05

A series of chelating amphiphiles and their gadolinium (Gd(III)) metal complexes have been synthesized and studied with respect to their neat and lyotropic liquid crystalline phase behavior. These amphiphiles have the ability to form ion-tunable self-assembly nanostructures and their associated Gd(III) complexes have potential as magnetic resonance imaging (MRI) contrast enhancement agents. The amphiphiles are composed of diethylenetriaminepentaacetic acid (DTPA) chelates conjugated to one or two oleyl chain(s) (DTPA-MO and DTPA-BO), or isoprenoid-type chain(s) of phytanyl (DTPA-MP and DTPA-BP). The thermal phase behavior of the neat amphiphiles was examined by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and cross polarizing optical microscopy (POM). Self-assembly of neat amphiphiles and their associated Gd complexes, as well as their lyotropic phase behavior in water and sodium acetate solutions of different ionic strengths, were examined by POM and small and wide angle X-ray scattering (SWAXS). All neat amphiphiles exhibited lamellar structures. The non-complexed amphiphiles showed a variety of lyotropic phases depending on the number and nature of the hydrophobic chain in addition to the ionic state of the hydration. Upon hydration with increased Na-acetate concentration and the subtle changes in the effective headgroup size, the interfacial curvature of the amphiphile increased, altering the lyotropic liquid crystalline structures towards higher order mesophases such as the gyroid (Ia3d) bicontinuous cubic phase. The chelation of Gd with the DTPA amphiphiles resulted in lamellar crystalline structures for all the neat amphiphiles. Upon hydration with water, the Gd-complexed mono-conjugates formed micellar or vesicular self-assemblies, whilst the bis-conjugates transformed only partially into lyotropic liquid crystalline mesophases.

Clinical, biological, and skin histopathologic effects of ionic macrocyclic and nonionic linear gadolinium chelates in a rat model of nephrogenic systemic fibrosis.

PubMed

Fretellier, Nathalie; Idée, Jean-Marc; Guerret, Sylviane; Hollenbeck, Claire; Hartmann, Daniel; González, Walter; Robic, Caroline; Port, Marc; Corot, Claire

2011-02-01

the purpose of this study was to compare the clinical, pathologic, and biochemical effects of repeated administrations of ionic macrocyclic or nonionic linear gadolinium chelates (GC) in rats with impaired renal function. rats submitted to subtotal nephrectomy were allocated to single injections of 2.5 mmol/kg of gadodiamide (nonionic linear chelate), nonformulated gadodiamide (ie, without the free ligand caldiamide), gadoterate (ionic macrocyclic chelate), or saline for 5 consecutive days. Blinded semi-quantitative histopathologic and immunohistochemical examinations of the skin were performed, as well as clinical, hematological, and biochemical follow-up. Rats were killed at day 11. Long-term (up to day 32) follow-up of rats was also performed in an auxiliary study. epidermal lesions (ulcerations and scabs) were found in 4 of the 10 rats treated with nonformulated gadodiamide. Two rats survived the study period. Inflammatory signs were observed in this group. No clinical, hematological, or biochemical signs were observed in the saline and gadoterate- or gadodiamide-treated groups. Plasma fibroblast growth factor-23 levels were significantly higher in the gadodiamide group than in the gadoterate group (day 11). Decreased plasma transferrin-bound iron levels were measured in the nonformulated gadodiamide group. Histologic lesions were in the range: nonformulated gadodiamide (superficial epidermal lesions, inflammation, necrosis, and increased cellularity in papillary dermis) > gadodiamide (small superficial epidermal lesions and signs of degradation of collagen fibers in the dermis) > gadoterate (very few pathologic lesions, similar to control rats). repeated administration of the nonionic linear GC gadodiamide to renally impaired rats is associated with more severe histologic lesions and higher FGF-23 plasma levels than the macrocyclic GC gadoterate.

Pericortical Enhancement on Delayed Postgadolinium Fluid-Attenuated Inversion Recovery Images in Normal Aging, Mild Cognitive Impairment, and Alzheimer Disease.

PubMed

Freeze, W M; Schnerr, R S; Palm, W M; Jansen, J F; Jacobs, H I; Hoff, E I; Verhey, F R; Backes, W H

2017-09-01

Breakdown of BBB integrity occurs in dementia and may lead to neurodegeneration and cognitive decline. We assessed whether extravasation of gadolinium chelate could be visualized on delayed postcontrast FLAIR images in older individuals with and without cognitive impairment. Seventy-four individuals participated in this study (15 with Alzheimer disease, 33 with mild cognitive impairment, and 26 with normal cognition). We assessed the appearance of pericortical enhancement after contrast administration, MR imaging markers of cerebrovascular damage, and medial temporal lobe atrophy. Three participants who were positive for pericortical enhancement (1 with normal cognition and 2 with mild cognitive impairment) were followed up for approximately 2 years. In vitro experiments with a range of gadolinium concentrations served to elucidate the mechanisms underlying the postcontrast FLAIR signals. Postcontrast pericortical enhancement was observed in 21 participants (28%), including 6 individuals with Alzheimer disease (40%), 10 with mild cognitive impairment (30%), and 5 with normal cognition (19%). Pericortical enhancement was positively associated with age ( P < .02) and ischemic stroke ( P < .05), but not with cognitive status ( P = .3). Foci with enhanced signal remained stable across time in all follow-up cases. The in vitro measurements confirmed that FLAIR imaging is highly sensitive for the detection of low gadolinium concentrations in CSF, but not in cerebral tissue. Postcontrast pericortical enhancement on FLAIR images occurs in older individuals with normal cognition, mild cognitive impairment, and dementia. It may represent chronic focal superficial BBB leakage. Future longitudinal studies are needed to determine its clinical significance. © 2017 by American Journal of Neuroradiology.

Macromolecular and Dendrimer Based Magnetic Resonance Contrast Agents

PubMed Central

Bumb, Ambika; Brechbiel, Martin W.; Choyke, Peter

2010-01-01

Magnetic resonance imaging (MRI) is a powerful imaging modality that can provide an assessment of function or molecular expression in tandem with anatomic detail. Over the last 20–25 years, a number of gadolinium based MR contrast agents have been developed to enhance signal by altering proton relaxation properties. This review explores a range of these agents from small molecule chelates, such as Gd-DTPA and Gd-DOTA, to macromolecular structures composed of albumin, polylysine, polysaccharides (dextran, inulin, starch), poly(ethylene glycol), copolymers of cystamine and cystine with GD-DTPA, and various dendritic structures based on polyamidoamine and polylysine (Gadomers). The synthesis, structure, biodistribution and targeting of dendrimer-based MR contrast agents are also discussed. PMID:20590365

Comparison of MRI properties between derivatized DTPA and DOTA gadolinium-dendrimer conjugates.

PubMed

Nwe, K; Bernardo, M; Regino, C A S; Williams, M; Brechbiel, M W

2010-08-15

In this report we directly compare the in vivo and in vitro MRI properties of gadolinium-dendrimer conjugates of derivatized acyclic diethylenetriamine-N,N',N',N'',N''-pentaacetic acid (1B4M-DTPA) and macrocyclic 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (C-DOTA). The metal-ligand chelates were pre-formed in alcohol prior to conjugation to the generation 4 PAMAM dendrimer (G4D), and the dendrimer-based agents were purified by Sephadex(R) G-25 column. The analysis and SE-HPLC data indicated chelate to dendrimer ratios of 30:1 and 28:1, respectively. Molar relaxivity measured at pH 7.4, 22 degrees C, and 3T are comparable (29.5 vs 26.9 mM(-1)s(-1)), and both conjugates are equally viable as MRI contrast agents based on the images obtained. The macrocyclic agent however exhibits a faster rate of clearance in vivo (t(1/2)=16 vs 29 min). Our conclusion is that the macrocyclic-based agent is the more suitable agent for in vivo use for these reasons combined with kinetic inertness associated with the Gd(III) DOTA complex stability properties. Published by Elsevier Ltd.

Comparison of MRI properties between derivatized DTPA and DOTA gadolinium-dendrimer conjugates

PubMed Central

Nwe, K.; Bernardo, M; Regino, C. A. S.; Williams, M; Brechbiel, M. W.

2010-01-01

In this report we directly compare the in vivo and in vitro MRI properties of gadolinium-dendrimer conjugates of derivatized acyclic diethylenetriamine-N,N’,N’,N’’, N’’-pentaacetic acid (1B4M-DTPA) and macrocyclic 1,4,7,10-tetraazacyclododecane-N,N’,N’’,N’’’-tetraacetic acid (C-DOTA). The metal-ligand chelates were pre-formed in alcohol prior to conjugation to the generation 4 PAMAM dendrimer (G4D), and the dendrimer-based agents were purified by Sephadex® G-25 column. The analysis and SE-HPLC data indicated chelate to dendrimer ratios of 30:1 and 28:1 respectively. Molar relaxivity measured at pH 7.4, 22°C, and 3T are comparable (29.5 vs. 26.9 mM−1s−1), and both conjugates are equally viable as MRI contrast agents based on the images obtained. The macrocyclic agent however exhibits a faster rate of clearance in vivo (t1/2 = 16 vs. 29 min.). Our conclusion is that the macrocyclic-based agent is the more suitable agent for in vivo use for these reasons combined with kinetic inertness associated with the Gd(III) DOTA complex stability properties. PMID:20663676

Gadolinium-enhanced cardiovascular magnetic resonance: administered dose in relationship to United States Food and Drug Administration (FDA) guidelines.

PubMed

Nacif, Marcelo S; Arai, Andrew E; Lima, Joao A C; Bluemke, David A

2012-02-29

Myocardial late gadolinium enhancement was originally validated using higher than label-recommended doses of gadolinium chelate. The objective of this study was to evaluate available evidence for various gadolinium dosing regimens used for CMR. The relationship of gadolinium dose warnings (due to nephrogenic systemic fibrosis) announced in 2008 to gadolinium dosing regimens was also examined. We conducted a meta-analysis of peer reviewed publications from January, 2004 to December, 2010. Major subject search headings (MeSh) terms from the National Library of Medicine's PubMed were: contrast media, gadolinium, heart, magnetic resonance imaging; searches were limited to human studies with abstracts published in English. Case reports, review articles, editorials, MRA related papers and all reports that did not indicate gadolinium type or weight-based dose were excluded. For all included references, full text was available to determine the total administered gadolinium dose on a per kg basis. Average and median dose values were weighted by the number of subjects in each study. 399 publications were identified in PubMed; 233 studies matched the inclusion criteria, encompassing 19,934 patients with mean age 54.2 ± 11.4 (range 9.3 to 76 years). 34 trials were related to perfusion testing and 199 to myocardial late gadolinium enhancement. In 2004, the weighted-median and weighted-mean contrast dose were 0.15 and 0.16 ± 0.06 mmol/kg, respectively. Median contrast doses for 2005-2010 were: 0.2 mmol/kg for all years, respectively. Mean contrast doses for the years 2005-2010 were: 0.19 ± 0.03, 0.18 ± 0.04, 0.18 ± 0.10, 0.18 ± 0.03, 0.18 ± 0.04 and 0.18 ± 0.04 mmol/kg, respectively (p for trend, NS). Gadopentetate dimeglumine was the most frequent gadolinium type [114 (48.9%) studies]. No change in mean gadolinium dose was present before, versus after the Food and Drug Administration (FDA) black box warning (p > 0.05). Three multi-center dose ranging trials have been published for cardiac MRI applications. CMR studies in the peer-reviewed published literature routinely use higher gadolinium doses than regulatory agencies indicated in the package leaflet. Clinical trials should be supported to determine the appropriate doses of gadolinium for CMR studies.

Vaginal distribution and retention of a multiparticulate drug delivery system, assessed by gamma scintigraphy and magnetic resonance imaging.

PubMed

Mehta, Samata; Verstraelen, Hans; Peremans, Kathelijne; Villeirs, Geert; Vermeire, Simon; De Vos, Filip; Mehuys, Els; Remon, Jean Paul; Vervaet, Chris

2012-04-15

For any new vaginal dosage form, the distribution and retention in the vagina has to be assessed by in vivo evaluation. We evaluated the vaginal distribution and retention of starch-based pellets in sheep as live animal model by gamma scintigraphy (using Indium-111 DTPA as radiolabel) and in women via magnetic resonance imaging (MRI, using a gadolinium chelate as contrast agent). A conventional cream formulation was used as reference in both studies. Cream and pellets were administered to sheep (n=6) in a two period-two treatment study and to healthy female volunteers (n=6) via a randomized crossover trial. Pellets (filled into hard gelatin capsule) and cetomacrogol cream, both labeled with Indium-111 DTPA (for gamma scintigraphy) or with gadolinium chelate (for MRI) were evaluated for their intravaginal distribution and retention over a 24h period. Spreading in the vagina was assessed based on the part of the vagina covered with formulation (expressed in relation to the total vaginal length). Vaginal retention of the formulation was quantified based on the radioactivity remaining in the vaginal area (sheep study), or qualitatively evaluated (women study). Both trials indicated a rapid distribution of the cream within the vagina as complete coverage of the vaginal mucosa was seen 1h after dose administration. Clearance of the cream was rapid: about 10% activity remained in the vaginal area of the sheep 12h post-administration, while after 8h only a thin layer of cream was detected on the vaginal mucosa of women. After disintegration of the hard gelatin capsule, the pellet formulation gradually distributed over the entire vaginal mucosa. Residence time of the pellets in the vagina was longer compared to the semi-solid formulation: after 24h 23 ± 7% radioactivity was detected in the vaginal area of the sheep, while in women the pellet formulation was still detected throughout the vagina. A multi-particulate system containing starch-based pellets was identified as a promising novel vaginal drug delivery system, resulting in complete coverage of the vaginal mucosa and long retention time. Copyright © 2012 Elsevier B.V. All rights reserved.

Target binding improves relaxivity in aptamer-gadolinium conjugates.

PubMed

Bernard, Elyse D; Beking, Michael A; Rajamanickam, Karunanithi; Tsai, Eve C; Derosa, Maria C

2012-12-01

MRI contrast agents (CA) have been heavily used over the past several decades to enhance the diagnostic value of the obtained images. From a design perspective, two avenues to improve the efficacy of contrast agents are readily evident: optimization of magnetic properties of the CA, and optimization of the pharmacokinetics and distribution of the CA in the patient. Contrast agents consisting of DNA aptamer-gadolinium(III) conjugates provide a single system in which these factors can be addressed simultaneously. In this proof-of-concept study, the 15mer thrombin aptamer was conjugated to diethylenetriaminepentaacetic (DTPA) dianhydride to form a monoamide derivative of the linear open-chain chelate present in the commonly used contrast agent Magnevist(®). The stability of the conjugated DNA aptamer-DTPA-Gd(III) chelate in a transmetallation study using Zn(II) was found to be similar to that reported for DTPA-Gd(III). Relaxivity enhancements of 35 ± 4 and 20 ± 1 % were observed in the presence of thrombin compared to a control protein at fields of 9.4 and 1.5 T, respectively. The inclusion of spacers between the aptamer and the DTPA to eliminate possible steric effects was also investigated but not found to improve the relaxation enhancement achieved in comparison to the unaltered aptamer conjugate.

Gadolinium Chelate Safety in Pregnancy: Barely Detectable Gadolinium Levels in the Juvenile Nonhuman Primate after in Utero Exposure.

PubMed

Prola-Netto, Joao; Woods, Mark; Roberts, Victoria H J; Sullivan, Elinor L; Miller, Christina Ann; Frias, Antonio E; Oh, Karen Y

2018-01-01

Purpose To determine whether gadolinium remains in juvenile nonhuman primate tissue after maternal exposure to intravenous gadoteridol during pregnancy. Materials and Methods Gravid rhesus macaques and their offspring (n = 10) were maintained, as approved by the institutional animal care and utilization committee. They were prospectively studied as part of a pre-existing ongoing research protocol to evaluate the effects of maternal malnutrition on placental and fetal development. On gestational days 85 and 135, they underwent placental magnetic resonance imaging after intravenous gadoteridol administration. Amniocentesis was performed on day 135 prior to administration of the second dose of gadoteridol. After delivery, the offspring were followed for 7 months. Tissue samples from eight different organs and from blood were harvested from each juvenile macaque. Gadolinium levels were measured by using inductively coupled plasma mass spectrometry. Results Gadolinium concentration in the amniotic fluid was 0.028 × 10 -5 %ID/g (percentage injected dose per gram of tissue) 50 days after administration of one gadoteridol dose. Gadolinium was most consistently detected in the femur (mean, 2.5 × 10 -5 %ID/g; range, [0.81-4.1] × 10 -5 %ID/g) and liver (mean, 0.15 × 10 -5 %ID/g; range, [0-0.26] × 10 -5 %ID/g). Levels were undetectable in the remaining sampled tissues, with the exception of one juvenile skin sample (0.07 × 10 -5 %ID/g), one juvenile spleen sample (0.039 × 10 -5 %ID/g), and one juvenile brain (0.095 × 10 -5 %ID/g) and kidney (0.13 × 10 -5 %ID/g) sample. Conclusion The presence of gadoteridol in the amniotic fluid after maternal injection enables confirmation that it crosses the placenta. Extremely low levels of gadolinium are found in juvenile macaque tissues after in utero exposure to two doses of gadoteridol, indicating that a very small amount of gadolinium persists after delivery. © RSNA, 2017.

The use of theranostic gadolinium-based nanoprobes to improve radiotherapy efficacy

PubMed Central

Sancey, L; Kotb, S; Roux, S; Dufort, S; Bianchi, A; Crémillieux, Y; Fries, P; Coll, J-L; Rodriguez-Lafrasse, C; Janier, M; Dutreix, M; Barberi-Heyob, M; Boschetti, F; Denat, F; Louis, C; Porcel, E; Lacombe, S; Le Duc, G; Deutsch, E; Perfettini, J-L; Detappe, A; Verry, C; Berbeco, R; Butterworth, K T; McMahon, S J; Prise, K M; Perriat, P; Tillement, O

2014-01-01

A new efficient type of gadolinium-based theranostic agent (AGuIX®) has recently been developed for MRI-guided radiotherapy (RT). These new particles consist of a polysiloxane network surrounded by a number of gadolinium chelates, usually 10. Owing to their small size (<5 nm), AGuIX typically exhibit biodistributions that are almost ideal for diagnostic and therapeutic purposes. For example, although a significant proportion of these particles accumulate in tumours, the remainder is rapidly eliminated by the renal route. In addition, in the absence of irradiation, the nanoparticles are well tolerated even at very high dose (10 times more than the dose used for mouse treatment). AGuIX particles have been proven to act as efficient radiosensitizers in a large variety of experimental in vitro scenarios, including different radioresistant cell lines, irradiation energies and radiation sources (sensitizing enhancement ratio ranging from 1.1 to 2.5). Pre-clinical studies have also demonstrated the impact of these particles on different heterotopic and orthotopic tumours, with both intratumoural or intravenous injection routes. A significant therapeutical effect has been observed in all contexts. Furthermore, MRI monitoring was proven to efficiently aid in determining a RT protocol and assessing tumour evolution following treatment. The usual theoretical models, based on energy attenuation and macroscopic dose enhancement, cannot account for all the results that have been obtained. Only theoretical models, which take into account the Auger electron cascades that occur between the different atoms constituting the particle and the related high radical concentrations in the vicinity of the particle, provide an explanation for the complex cell damage and death observed. PMID:24990037

Aiming for a shorter rheumatoid arthritis MRI protocol: can contrast-enhanced MRI replace T2 for the detection of bone marrow oedema?

PubMed

Stomp, Wouter; Krabben, Annemarie; van der Heijde, Désirée; Huizinga, Tom W J; Bloem, Johan L; van der Helm-van Mil, Annette H M; Reijnierse, Monique

2014-10-01

To determine whether T1 post-gadolinium chelate images (T1Gd) can replace T2-weighted images (T2) for evaluating bone marrow oedema (BME), thereby allowing a shorter magnetic resonance imaging (MRI) protocol in rheumatoid arthritis (RA). In 179 early arthritis patients and 43 advanced RA patients, wrist and metacarpophalangeal joints were examined on a 1.5-T extremity MRI system with a standard protocol (coronal T1, T2 fat-saturated and coronal and axial T1 fat-saturated after Gd). BME was scored according to OMERACT RAMRIS by two observers with and without T2 images available. Agreement was assessed using intraclass correlation coefficients (ICCs) for semi-quantitative scores and test characteristics with T2 images as reference. Agreement between scores based on T2 and T1Gd images was excellent ICC (0.80-0.99). At bone level, sensitivity and specificity of BME on T1Gd compared to T2 were high for both patient groups and both readers (all ≥80 %). T1Gd and T2 images are equally suitable for evaluating BME. Because contrast is usually administered to assess (teno)synovitis, a short MRI protocol of T1 and T1Gd is sufficient in RA. • Bone marrow oedema scores are equal on T2 and T1-Gd-chelate enhanced sequences. • Agreement between scores based on T2 and T1-Gd-chelate images was excellent. • Sensitivity and specificity for presence of bone marrow oedema were high. • A short protocol without T2 images suffices in rheumatoid arthritis patients.

Gadolinium-conjugated PLA-PEG nanoparticles as liver targeted molecular MRI contrast agent.

PubMed

Chen, Zhijin; Yu, Dexin; Liu, Chunxi; Yang, Xiaoyan; Zhang, Na; Ma, Chunhong; Song, Jibin; Lu, Zaijun

2011-09-01

A nanoparticle magnetic resonance imaging (MRI) contrast agent targeted to liver was developed by conjugation of gadolinium (Gd) chelate groups onto the biocompatible poly(l-lactide)-block-poly (ethylene glycol) (PLA-PEG) nanoparticles. PLA-PEG conjugated with diethylenetriaminopentaacetic acid (DTPA) was used to formulate PLA-PEG-DTPA nanoparticles by solvent diffusion method, and then Gd was loaded onto the nanoparticles by chelated with the unfolding DTPA on the surface of the PLA-PEG-DTPA nanoparticles. The mean size of the nanoparticles was 265.9 ± 6.7 nm. The relaxivity of the Gd-labeled nanoparticles was measured, and the distribution in vivo was evaluated in rats. Compared with conventional contrast agent (Magnevist), the Gd-labeled PLA-PEG nanoparticles showed significant enhancement both on liver targeting ability and imaging signal intensity. The T(1) and T(2) relaxivities per [Gd] of the Gd-labeled nanoparticles was 18.865 mM(-1) s(-1) and 24.863 mM(-1) s(-1) at 3 T, respectively. In addition, the signal intensity in vivo was stronger comparing with the Gd-DTPA and the T(1) weight time was lasting for 4.5 h. The liver targeting efficiency of the Gd-labeled PLA-PEG nanoparticles in rats was 14.57 comparing with Magnevist injection. Therefore, the Gd-labeled nanoparticles showed the potential as targeting molecular MRI contrast agent for further clinical utilization.

Anthropogenic gadolinium anomalies and rare earth elements in the water of Atibaia River and Anhumas Creek, Southeast Brazil.

PubMed

de Campos, Francisco Ferreira; Enzweiler, Jacinta

2016-05-01

The concentrations of rare earth elements (REE), measured in water samples from Atibaia River and its tributary Anhumas Creek, Brazil, present excess of dissolved gadolinium. Such anthropogenic anomalies of Gd in water, already described in other parts of the world, result from the use of stable and soluble Gd chelates as contrast agents in magnetic resonance imaging. Atibaia River constitutes the main water supply of Campinas Metropolitan area, and its basin receives wastewater effluents. The REE concentrations in water samples were determined in 0.22-μm pore size filtered samples, without and after preconcentration by solid-phase extraction with bis-(2-ethyl-hexyl)-phosphate. This preconcentration method was unable to retain the anthropogenic Gd quantitatively. The probable reason is that the Gd chelates dissociate slowly in acidic media to produce the free ion that is retained by the phosphate ester. Strong correlations between Gd and constituents or parameters associated with effluents confirmed the source of most Gd in water samples as anthropogenic. The shale-normalized REE patterns of Atibaia River and Anhumas Creek water samples showed light and heavy REE enrichment trends, respectively. Also, positive Ce anomalies in many Atibaia River samples, as well as the strong correlations of the REE (except Gd) with terrigenous elements, imply that inorganic colloidal particles contributed to the REE measured values.

Time-resolved MR angiography of renal artery stenosis in a swine model at 3 Tesla using gadobutrol with digital subtraction angiography correlation.

PubMed

Morelli, John N; Ai, Fei; Runge, Val M; Zhang, Wei; Li, Xiaoming; Schmitt, Peter; McNeal, Gary; Michaely, Henrick J; Schoenberg, Stefan O; Miller, Matthew; Gerdes, Clint M; Sincleair, Spencer T; Spratt, Heidi; Attenberger, Ulrike I

2012-09-01

To establish the minimum dose required for detection of renal artery stenosis using high temporal resolution, contrast enhanced MR angiography (MRA) in a porcine model. Surgically created renal artery stenoses were imaged with 3 Tesla MR and digital subtraction angiography (DSA) in 12 swine in this IACUC approved protocol. Gadobutrol was injected intravenously at doses of 0.5, 1, 2, and 4 mL for time-resolved MRA (1.5 × 1.5 mm(2) spatial resolution). Region of interest analysis was performed together with stenosis assessment and qualitative evaluation by two blinded readers. Mean signal to noise ratio (SNR) and contrast to noise ratio (CNR) values were statistically significantly less with the 0.5-mL protocol (P < 0.001). There were no statistically significant differences among the other evaluated doses. Both readers found 10/12 cases with the 0.5-mL protocol to be of inadequate diagnostic quality (κ = 1.0). All other scans were found to be adequate for diagnosis. Accuracies in distinguishing between mild/insignificant (<50%) and higher grade stenoses (>50%) were comparable among the higher-dose protocols (sensitivities 73-93%, specificities 62-100%). Renal artery stenosis can be assessed with very low doses (~0.025 mmol/kg bodyweight) of a high concentration, high relaxivity gadolinium chelate formulation in a swine model, results which are promising with respect to limiting exposure to gadolinium based contrast agents. Copyright © 2012 Wiley Periodicals, Inc.

Synthesis and evaluation of nanoglobular macrocyclic Mn(II) chelate conjugates as non-gadolinium(III) MRI contrast agents.

PubMed

Tan, Mingqian; Ye, Zhen; Jeong, Eun-Kee; Wu, Xueming; Parker, Dennis L; Lu, Zheng-Rong

2011-05-18

Because of the recent observation of the toxic side effects of Gd(III) based MRI contrast agents in patients with impaired renal function, there is strong interest on developing alternative contrast agents for MRI. In this study, macrocyclic Mn(II) chelates were conjugated to nanoglobular carriers, lysine dendrimers with a silsesquioxane core, to synthesize non-Gd(III) based MRI contrast agents. A generation 3 nanoglobular conjugate of Mn(II)-1,4,7-triaazacyclononane-1,4,7-triacetate-GA amide (G3-NOTA-Mn) was also synthesized and evaluated. The per ion T(1) and T(2) relaxivities of G2, G3, G4 nanoglobular Mn(II)-DOTA monoamide conjugates decreased with increasing generation of the carriers. The T(1) relaxivities of G2, G3, and G4 nanoglobular Mn(II)-DOTA conjugates were 3.3, 2.8, and 2.4 mM(-1) s(-1) per Mn(II) chelate at 3 T, respectively. The T(1) relaxivity of G3-NOTA-Mn was 3.80 mM(-1) s(-1) per Mn(II) chelate at 3 T. The nanoglobular macrocyclic Mn(II) chelate conjugates showed good in vivo stability and were readily excreted via renal filtration. The conjugates resulted in much less nonspecific liver enhancement than MnCl(2) and were effective for contrast-enhanced tumor imaging in nude mice bearing MDA-MB-231 breast tumor xenografts at a dose of 0.03 mmol Mn/kg. The nanoglobular macrocyclic Mn(II) chelate conjugates are promising nongadolinium based MRI contrast agents.

Analytical Interference in Serum Iron Determination Reveals Iron Versus Gadolinium Transmetallation With Linear Gadolinium-Based Contrast Agents

PubMed Central

Fretellier, Nathalie; Poteau, Nathalie; Factor, Cécile; Mayer, Jean-François; Medina, Christelle; Port, Marc; Idée, Jean-Marc; Corot, Claire

2014-01-01

Objectives The purposes of this study were to evaluate the risk for analytical interference with gadolinium-based contrast agents (GBCAs) for the colorimetric measurement of serum iron (Fe3+) and to investigate the mechanisms involved. Materials and Methods Rat serum was spiked with several concentrations of all molecular categories of GBCAs, ligands, or “free” soluble gadolinium (Gd3+). Serum iron concentration was determined by 2 different colorimetric methods at pH 4.0 (with a Vitros DT60 analyzer or a Cobas Integra 400 analyzer). Secondly, the cause of interference was investigated by (a) adding free soluble Gd3+ or Mn2+ to serum in the presence of gadobenic acid or gadodiamide and (b) electrospray ionization mass spectrometry. Results Spurious decrease in serum Fe3+ concentration was observed with all linear GBCAs (only with the Vitros DT60 technique occurring at pH 4.0) but not with macrocyclic GBCAs or with free soluble Gd3+. Spurious hyposideremia was also observed with the free ligands present in the pharmaceutical solutions of the linear GBCAs gadopentetic acid and gadodiamide (ie, diethylene triamine pentaacetic acid and calcium-diethylene triamine pentaacetic acid bismethylamide, respectively), suggesting the formation of Fe-ligand chelate. Gadobenic acid-induced interference was blocked in a concentration-dependent fashion by adding a free soluble Gd3+ salt. Conversely, Mn2+, which has a lower affinity than Gd3+ and Fe3+ for the ligand of gadobenic acid (ie, benzyloxypropionic diethylenetriamine tetraacetic acid), was less effective (interference was only partially blocked), suggesting an Fe3+ versus Gd3+ transmetallation phenomenon at pH 4.0. Similar results were observed with gadodiamide. Mass spectrometry detected the formation of Fe-ligand with all linear GBCAs tested in the presence of Fe3+ and the disappearance of Fe-ligand after the addition of free soluble Gd3+. No Fe-ligand chelate was found in the case of the macrocyclic GBCA gadoteric acid. Conclusions Macrocyclic GBCAs induced no interference with colorimetric methods for iron determination, whereas negative interference was observed with linear GBCAs using a Vitros DT60 analyzer. This interference of linear GBCAs seems to be caused by the excess of ligand and/or an Fe3+ versus Gd3+ transmetallation phenomenon. PMID:24943092

Gadolinium-based Contrast Media, Cerebrospinal Fluid and the Glymphatic System: Possible Mechanisms for the Deposition of Gadolinium in the Brain.

PubMed

Taoka, Toshiaki; Naganawa, Shinji

2018-04-10

After Kanda's first report in 2014 on gadolinium (Gd) deposition in brain tissue, a considerable number of studies have investigated the explanation for the observation. Gd deposition in brain tissue after repeated administration of gadolinium-based contrast medium (GBCM) has been histologically proven, and chelate stability has been shown to affect the deposition. However, the mechanism for this deposition has not been fully elucidated. Recently, a hypothesis was introduced that involves the 'glymphatic system', which is a coined word that combines 'gl' for glia cell and 'lymphatic' system. According to this hypothesis, the perivascular space functions as a conduit for cerebrospinal fluid to flow into the brain parenchyma. The perivascular space around the arteries allows cerebrospinal fluid to enter the interstitial space of the brain tissue through water channels controlled by aquaporin 4. The cerebrospinal fluid entering the interstitial space clears waste proteins from the tissue. It then flows into the perivascular space around the vein and is discharged outside the brain. In addition to the hypothesis regarding the glymphatic system, some reports have described that after GBCM administration, some of the GBCM distributes through systemic blood circulation and remains in other compartments including the cerebrospinal fluid. It is thought that the GBCM distributed into the cerebrospinal fluid cavity via the glymphatic system may remain in brain tissue for a longer duration compared to the GBCM in systemic circulation. Glymphatic system may of course act as a clearance system for GBCM from brain tissue. Based on these findings, the mechanism for Gd deposition in the brain will be discussed in this review. The authors speculate that the glymphatic system may be the major contributory factor to the deposition and clearance of gadolinium in brain tissue.

Gadolinium-based Contrast Media, Cerebrospinal Fluid and the Glymphatic System: Possible Mechanisms for the Deposition of Gadolinium in the Brain

PubMed Central

Taoka, Toshiaki; Naganawa, Shinji

2018-01-01

After Kanda’s first report in 2014 on gadolinium (Gd) deposition in brain tissue, a considerable number of studies have investigated the explanation for the observation. Gd deposition in brain tissue after repeated administration of gadolinium-based contrast medium (GBCM) has been histologically proven, and chelate stability has been shown to affect the deposition. However, the mechanism for this deposition has not been fully elucidated. Recently, a hypothesis was introduced that involves the ‘glymphatic system’, which is a coined word that combines ‘gl’ for glia cell and ‘lymphatic’ system. According to this hypothesis, the perivascular space functions as a conduit for cerebrospinal fluid to flow into the brain parenchyma. The perivascular space around the arteries allows cerebrospinal fluid to enter the interstitial space of the brain tissue through water channels controlled by aquaporin 4. The cerebrospinal fluid entering the interstitial space clears waste proteins from the tissue. It then flows into the perivascular space around the vein and is discharged outside the brain. In addition to the hypothesis regarding the glymphatic system, some reports have described that after GBCM administration, some of the GBCM distributes through systemic blood circulation and remains in other compartments including the cerebrospinal fluid. It is thought that the GBCM distributed into the cerebrospinal fluid cavity via the glymphatic system may remain in brain tissue for a longer duration compared to the GBCM in systemic circulation. Glymphatic system may of course act as a clearance system for GBCM from brain tissue. Based on these findings, the mechanism for Gd deposition in the brain will be discussed in this review. The authors speculate that the glymphatic system may be the major contributory factor to the deposition and clearance of gadolinium in brain tissue. PMID:29367513

Gadolinium-based nanoparticles to improve the hadrontherapy performances.

PubMed

Porcel, Erika; Tillement, Olivier; Lux, François; Mowat, Pierre; Usami, Noriko; Kobayashi, Katsumi; Furusawa, Yoshiya; Le Sech, Claude; Li, Sha; Lacombe, Sandrine

2014-11-01

Nanomedicine is proposed as a novel strategy to improve the performance of radiotherapy. High-Z nanoparticles are known to enhance the effects of ionizing radiation. Recently, multimodal nanoparticles such as gadolinium-based nanoagents were proposed to amplify the effects of x-rays and g-rays and to improve MRI diagnosis. For tumors sited in sensitive tissues, childhood cases and radioresistant cancers, hadrontherapy is considered superior to x-rays and g-rays. Hadrontherapy, based on fast ion radiation, has the advantage of avoiding damage to the tissues behind the tumor; however, the damage caused in front of the tumor is its major limitation. Here, we demonstrate that multimodal gadolinium-based nanoparticles amplify cell death with fast ions used as radiation. Molecular scale experiments give insights into the mechanisms underlying the amplification of radiation effects. This proof-of-concept opens up novel perspectives for multimodal nanomedicine in hadrontherapy, ultimately reducing negative radiation effects in healthy tissues in front of the tumor. Gadolinium-chelating polysiloxane nanoparticles were previously reported to amplify the anti-tumor effects of x-rays and g-rays and to serve as MRI contrast agents. Fast ion radiation-based hadrontherapy avoids damage to the tissues behind the tumor, with a major limitation of tissue damage in front of the tumor. This study demonstrates a potential role for the above nanoagents in optimizing hadrontherapy with preventive effects in healthy tissue and amplified cell death in the tumor. Copyright © 2014 Elsevier Inc. All rights reserved.

Evaluation of Novel 64Cu-Labeled Theranostic Gadolinium-Based Nanoprobes in HepG2 Tumor-Bearing Nude Mice.

PubMed

Hu, Pengcheng; Cheng, Dengfeng; Huang, Tao; Banizs, Anna B; Xiao, Jie; Liu, Guobing; Chen, Quan; Wang, Yuenan; He, Jiang; Shi, Hongcheng

2017-09-06

Radiation therapy of liver cancer is limited by low tolerance of the liver to radiation. Radiosensitizers can effectively reduce the required radiation dose. AGuIX nanoparticles are small, multifunctional gadolinium-based nanoparticles that can carry radioisotopes or fluorescent markers for single-photon emission computed tomography (SPECT), positron emission tomography (PET), fluorescence imaging, and even multimodality imaging. In addition, due to the high atomic number of gadolinium, it can also serve as a tumor radiation sensitizer. It is critical to define the biodistribution and pharmacokinetics of these gadolinium-based nanoparticles to quantitate the magnitude and duration of their retention within the tumor microenvironment during radiotherapy. Therefore, in this study, we successfully labeled AGuIX with 64 Cu through the convenient built-in chelator. The biodistribution studies indicated that the radiotracer 64 Cu-AGuIX accumulates to high levels in the HepG2 xenograft of nude mice, suggesting that it would be a potential theranostic nanoprobe for image-guided radiotherapy in HCC. We also used a transmission electron microscope to confirm AGuIX uptake in the HepG2 cells. In radiation therapy studies, a decrease in 18 F-FDG uptake was observed in the xenografts of the nude mice irradiated with AGuIX, which was injected 1 h before. These results provide proof-of-concept that AGuIX can be used as a theranostic radiosensitizer for PET imaging to guide radiotherapy for liver cancer.

Evaluation of Novel 64Cu-Labeled Theranostic Gadolinium-Based Nanoprobes in HepG2 Tumor-Bearing Nude Mice

NASA Astrophysics Data System (ADS)

Hu, Pengcheng; Cheng, Dengfeng; Huang, Tao; Banizs, Anna B.; Xiao, Jie; Liu, Guobing; Chen, Quan; Wang, Yuenan; He, Jiang; Shi, Hongcheng

2017-09-01

Radiation therapy of liver cancer is limited by low tolerance of the liver to radiation. Radiosensitizers can effectively reduce the required radiation dose. AGuIX nanoparticles are small, multifunctional gadolinium-based nanoparticles that can carry radioisotopes or fluorescent markers for single-photon emission computed tomography (SPECT), positron emission tomography (PET), fluorescence imaging, and even multimodality imaging. In addition, due to the high atomic number of gadolinium, it can also serve as a tumor radiation sensitizer. It is critical to define the biodistribution and pharmacokinetics of these gadolinium-based nanoparticles to quantitate the magnitude and duration of their retention within the tumor microenvironment during radiotherapy. Therefore, in this study, we successfully labeled AGuIX with 64Cu through the convenient built-in chelator. The biodistribution studies indicated that the radiotracer 64Cu-AGuIX accumulates to high levels in the HepG2 xenograft of nude mice, suggesting that it would be a potential theranostic nanoprobe for image-guided radiotherapy in HCC. We also used a transmission electron microscope to confirm AGuIX uptake in the HepG2 cells. In radiation therapy studies, a decrease in 18F-FDG uptake was observed in the xenografts of the nude mice irradiated with AGuIX, which was injected 1 h before. These results provide proof-of-concept that AGuIX can be used as a theranostic radiosensitizer for PET imaging to guide radiotherapy for liver cancer.

Engineering an antibody with picomolar affinity to DOTA chelates of multiple radionuclides for pretargeted radioimmunotherapy and imaging

PubMed Central

Orcutt, Kelly Davis; Slusarczyk, Adrian L; Cieslewicz, Maryelise; Ruiz-Yi, Benjamin; Bhushan, Kumar R; Frangioni, John V; Wittrup, K Dane

2014-01-01

Introduction In pretargeted radioimmunotherapy (PRIT), a bifunctional antibody is administered and allowed to pre-localize to tumor cells. Subsequently, a chelated radionuclide is administered and captured by cell-bound antibody while unbound hapten clears rapidly from the body. We aim to engineer high-affinity binders to DOTA chelates for use in PRIT applications. Methods We mathematically modeled antibody and hapten pharmacokinetics to analyze hapten tumor retention as a function of hapten binding affinity. Motivated by model predictions, we used directed evolution and yeast surface display to affinity mature the 2D12.5 antibody to 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), reformatted as a single chain variable fragment (scFv). Results Modeling predicts that for high antigen density and saturating bsAb dose, a hapten binding affinity of 100 picomolar (pM) is needed for near-maximal hapten retention. We affinity matured 2D12.5 with an initial binding constant of about 10 nanomolar (nM) to DOTA-yttrium chelates. Affinity maturation resulted in a 1000-fold affinity improvement to biotinylated DOTA-yttrium, yielding an 8.2 ± 1.9 picomolar binder. The high-affinity scFv binds DOTA complexes of lutetium and gadolinium with similar picomolar affinity and indium chelates with low nanomolar affinity. When engineered into a bispecific antibody construct targeting carcinoembryonic antigen (CEA), pretargeted high-affinity scFv results in significantly higher tumor retention of a 111In-DOTA hapten compared to pretargeted wild-type scFv in a xenograft mouse model. Conclusions We have engineered a versatile, high-affinity DOTA-chelate-binding scFv. We anticipate it will prove useful in developing pretargeted imaging and therapy protocols to exploit the potential of a variety of radiometals. PMID:21315278

XFM demonstrates preferential accumulation of a vanadyl-based MRI contrast agent in murine colonic tumors

PubMed Central

Mustafi, Devkumar; Ward, Jesse; Dougherty, Urszula; Bissonnette, Marc; Hart, John; Vogt, Stefan; Karczmar, Gregory S.

2016-01-01

Contrast agents that specifically enhance cancers on MRI would allow earlier detection. Vanadyl-based chelates (VCs) selectively enhance rodent cancers on MRI, suggesting selective uptake of VCs by cancers. Here we report X-ray fluorescence microscopy (XFM) of VC uptake by murine colon cancer. Colonic tumors in mice treated with azoxymethane/dextran sulfate sodium were identified by MRI. Then a gadolinium-based contrast agent and a VC were injected I.V.; mice were sacrificed and colons sectioned. VC distribution was sampled at 120 minutes after injection to evaluate the long term accumulation. Gadolinium distribution was sampled at 10 minutes after injection due to its rapid washout. XFM was performed on 72 regions of normal and cancerous colon from 5 normal mice and 4 cancer-bearing mice. XFM showed that all gadolinium was extracellular with similar concentrations in colon cancers and normal colon. In contrast, the average VC concentration was 2-fold higher in cancers vs. normal tissue (p<0.002). Cancers also contained numerous ‘hot spots’ with intracellular VC concentrations 6-fold higher than the concentration in normal colon (p<0.0001). No ‘hot spots’ were detected in normal colon. This is the first direct demonstration that VCs selectively accumulate in cancer cells, and thus may improve cancer detection. PMID:25813904

Cell-permeable Ln(III) chelate-functionalized InP quantum dots as multimodal imaging agents.

PubMed

Stasiuk, Graeme J; Tamang, Sudarsan; Imbert, Daniel; Poillot, Cathy; Giardiello, Marco; Tisseyre, Céline; Barbier, Emmanuel L; Fries, Pascal Henry; de Waard, Michel; Reiss, Peter; Mazzanti, Marinella

2011-10-25

Quantum dots (QDs) are ideal scaffolds for the development of multimodal imaging agents, but their application in clinical diagnostics is limited by the toxicity of classical CdSe QDs. A new bimodal MRI/optical nanosized contrast agent with high gadolinium payload has been prepared through direct covalent attachment of up to 80 Gd(III) chelates on fluorescent nontoxic InP/ZnS QDs. It shows a high relaxivity of 900 mM(-1) s(-1) (13 mM(-1 )s(-1) per Gd ion) at 35 MHz (0.81 T) and 298 K, while the bright luminescence of the QDs is preserved. Eu(III) and Tb(III) chelates were also successfully grafted to the InP/ZnS QDs. The absence of energy transfer between the QD and lanthanide emitting centers results in a multicolor system. Using this convenient direct grafting strategy additional targeting ligands can be included on the QD. Here a cell-penetrating peptide has been co-grafted in a one-pot reaction to afford a cell-permeable multimodal multimeric MRI contrast agent that reports cellular localization by fluorescence and provides high relaxivity and increased tissue retention with respect to commercial contrast agents.

Non-invasive magnetic resonance imaging follow-up of sono-sensitive liposome tumor delivery and controlled release after high-intensity focused ultrasound.

PubMed

Fowler, Robert Andrew; Fossheim, Sigrid L; Mestas, Jean-Louis; Ngo, Jacqueline; Canet-Soulas, Emmanuelle; Lafon, Cyril

2013-12-01

This work examines the use of lanthanide-based contrast agents and magnetic resonance imaging in monitoring liposomal behavior in vivo. Dysprosium (Dy) and gadolinium (Gd) chelates, Dy-diethylenetriaminepentaacetic acid bismethylamide (Dy-DTPA-BMA) and Gd-DTPA-BMA, were encapsulated in pegylated distearoylphosphatidylethanolamine-based (saturated) liposomes, and then intravenously injected into Copenhagen rats with subcutaneous Dunning AT2 xenografts. Liposome-encapsulated Dy chelate shortens transverse relaxation times (T(2) and T(2)*) of tissue; thus, liposomal accumulation in the tumor can be monitored by observing the decrease in T(2)* relaxation time over time. The tumor was treated at the time of maximum liposomal accumulation (48 h) with confocal, cavitating high-intensity focused ultrasound to induce liposomal payload release. Using liposome-encapsulated Gd chelate at high enough concentrations and saturated liposomal phospholipids induces an exchange-limited longitudinal (T(1)) relaxation when the liposomes are intact; when the liposomes are released, exchange limitation is relieved, thus allowing in vivo observation of payload release as a decrease in tumor T(1). Copyright © 2013 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Dual modal ultra-bright nanodots with aggregation-induced emission and gadolinium-chelation for vascular integrity and leakage detection.

PubMed

Feng, Guangxue; Li, Jackson Liang Yao; Claser, Carla; Balachander, Akhila; Tan, Yingrou; Goh, Chi Ching; Kwok, Immanuel Weng Han; Rénia, Laurent; Tang, Ben Zhong; Ng, Lai Guan; Liu, Bin

2018-01-01

The study of blood brain barrier (BBB) functions is important for neurological disorder research. However, the lack of suitable tools and methods has hampered the progress of this field. Herein, we present a hybrid nanodot strategy, termed AIE-Gd dots, comprising of a fluorogen with aggregation-induced emission (AIE) characteristics as the core to provide bright and stable fluorescence for optical imaging, and gadolinium (Gd) for accurate quantification of vascular leakage via inductively-coupled plasma mass spectrometry (ICP-MS). In this report, we demonstrate that AIE-Gd dots enable direct visualization of brain vascular networks under resting condition, and that they form localized punctate aggregates and accumulate in the brain tissue during experimental cerebral malaria, indicative of hemorrhage and BBB malfunction. With its superior detection sensitivity and multimodality, we hereby propose that AIE-Gd dots can serve as a better alternative to Evans blue for visualization and quantification of changes in brain barrier functions. Copyright © 2017. Published by Elsevier Ltd.

A new contrast media for functional MR urography: Gd-MAG3.

PubMed

Algin, Oktay

2011-07-01

Tc-99m-MAG3 (tubular agent) provides high imaging quality and extraction efficiency; and has become one of the most widely used agent for scintigraphic examinations of urinary system pathologies and renal transplants. Recently, it was reported that functional magnetic resonance urography (FMRU) can be sufficient in detection of urinary tract obstruction, renal artery stenosis, calculation of kidney functions and evaluation of renal transplants. However the pharmacokinetics of magnetic resonance (MR) contrast-media used in FMRU and Tc-99m-MAG3 differs from each other. This may cause discordant results between the FMRU and most of the scintigraphic studies. To our knowledge, there is no contrast-media which is specific for FMRU. A kidney specific contrast material can be developed for FMRU studies as well. MAG3 is a good candidate for this chelation. In conclusion, MR imaging (MRI) will be the most useful and important technique for morphologic-functional evaluation of urinary system. FMRU examinations performed with MAG3 chelated gadolinium can be sufficient for the complete evaluation of urinary tract even in patients with impaired renal functions ("all in one MRI"). MRI has some important advantages including no risk for radiation exposure, high temporal and spatial resolution, no need for nephrotoxic contrast agent; besides being a fast and feasible technique. Gadolinium-containing contrast agents may cause a life-threatening adverse reaction known as nephrogenic systemic fibrosis in patients with severe renal impairment, but Gd-MAG3 may reduce the risk of nephrogenic systemic fibrosis due to its higher extraction capacity and other features. Copyright © 2011 Elsevier Ltd. All rights reserved.

Primed infusion with delayed equilibrium of Gd.DTPA for enhanced imaging of small pulmonary metastases.

PubMed

Kalber, Tammy L; Campbell-Washburn, Adrienne E; Siow, Bernard M; Sage, Elizabeth; Price, Anthony N; Ordidge, Katherine L; Walker-Samuel, Simon; Janes, Sam M; Lythgoe, Mark F

2013-01-01

To use primed infusions of the magnetic resonance imaging (MRI) contrast agent Gd.DTPA (Magnevist), to achieve an equilibrium between blood and tissue (eqMRI). This may increase tumor Gd concentrations as a novel cancer imaging methodology for the enhancement of small tumor nodules within the low signal-to-noise background of the lung. A primed infusion with a delay before equilibrium (eqMRI) of the Gd(III) chelator Gd.DTPA, via the intraperitoneal route, was used to evaluate gadolinium tumor enhancement as a function of a bolus injection, which is applied routinely in the clinic, compared to gadolinium maintained at equilibrium. A double gated (respiration and cardiac) spin-echo sequence at 9.4T was used to evaluate whole lungs pre contrast and then at 15 (representative of bolus enhancement), 25 and 35 minutes (representative of eqMRI). This was carried out in two lung metastasis models representative of high and low tumor cell seeding. Lungs containing discrete tumor nodes where inflation fixed and taken for haematoxylin and eosin staining as well as CD34 staining for correlation to MRI. We demonstrate that sustained Gd enhancement, afforded by Gd equilibrium, increases the detection of pulmonary metastases compared to bolus enhancement and those tumors which enhance at equilibrium are sub-millimetre in size (<0.7 mm(2)) with a similar morphology to early bronchoalveolar cell carcinomas. As Gd-chelates are routinely used in the clinic for detecting tumors by MRI, this methodology is readily transferable to the clinic and advances MRI as a methodology for the detection of small pulmonary tumors.

Phosphinic acid functionalized polyazacycloalkane chelators for radiodiagnostics and radiotherapeutics: unique characteristics and applications.

PubMed

Notni, Johannes; Šimeček, Jakub; Wester, Hans-Jürgen

2014-06-01

Given the wide application of positron emission tomography (PET), positron-emitting metal radionuclides have received much attention recently. Of these, gallium-68 has become particularly popular, as it is the only PET nuclide commercially available from radionuclide generators, therefore allowing local production of PET radiotracers independent of an on-site cyclotron. Hence, interest in optimized bifunctional chelators for the elaboration of (68) Ga-labeled bioconjugates has been rekindled as well, resulting in the development of improved triazacyclononane-triphosphinate (TRAP) ligand structures. The most remarkable features of these ligands are unparalleled selectivity for Ga(III) , rapid Ga(III) complexation kinetics, extraordinarily high thermodynamic stability, and kinetic inertness of the respective Ga(III) chelates. As a result, TRAP chelators exhibit very favorable (68) Ga-labeling properties. Based on the scaffolds NOPO (1,4,7-triazacyclononane-1,4-bis[methylene(hydroxymethyl)phosphinic acid]-7-[methylene(2-carboxyethyl)phosphinic acid]) and TRAP-Pr, tailored for convenient preparation of (68) Ga-labeled monomeric and multimeric bioconjugates, a variety of novel (68) Ga radiopharmaceuticals have been synthesized. These include bisphosphonates, somatostatin receptor ligands, prostate-specific membrane antigen (PSMA)-targeting peptides, and cyclic RGD pentapeptides, for in vivo PET imaging of bone, neuroendocrine tumors, prostate cancer, and integrin expression, respectively. Furthermore, TRAP-based (68) Ga-labeled gadolinium(III) complexes have been proposed as bimodal probes for PET/MRI, and a cyclen-based analogue of TRAP-Pr has been suggested for the elaboration of targeted radiotherapeutics comprising radiolanthanide ions. Thus, polyazacycloalkane-based polyphosphinic acid chelators are a powerful toolbox for pharmaceutical research, particularly for the development of (68) Ga radiopharmaceuticals. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Heterogeneous intratumoral distribution of gadolinium nanoparticles within U87 human glioblastoma xenografts unveiled by micro-PIXE imaging.

PubMed

Carmona, Asuncion; Roudeau, Stéphane; L'Homel, Baptiste; Pouzoulet, Frédéric; Bonnet-Boissinot, Sarah; Prezado, Yolanda; Ortega, Richard

2017-04-15

Metallic nanoparticles have great potential in cancer radiotherapy as theranostic drugs since, they serve simultaneously as contrast agents for medical imaging and as radio-therapy sensitizers. As with other anticancer drugs, intratumoral diffusion is one of the main limiting factors for therapeutic efficiency. To date, a few reports have investigated the intratumoral distribution of metallic nanoparticles. The aim of this study was to determine the quantitative distribution of gadolinium (Gd) nanoparticles after direct intratumoral injection within U87 human glioblastoma tumors grafted in mice, using micro-PIXE (Particle Induced X-ray Emission) imaging. AGuIX (Activation and Guiding of Irradiation by X-ray) 3 nm particles composed of a polysiloxane network surrounded by gadolinium chelates were used. PIXE results indicate that the direct injection of Gd nanoparticles in tumors results in their heterogeneous diffusion, probably related to variations in tumor density. All tumor regions contain Gd, but with markedly different concentrations, with a more than 250-fold difference. Also Gd can diffuse to the healthy adjacent tissue. This study highlights the usefulness of mapping the distribution of metallic nanoparticles at the intratumoral level, and proposes PIXE as an imaging modality to probe the quantitative distribution of metallic nanoparticles in tumors from experimental animal models with micrometer resolution. Copyright © 2017 Elsevier Inc. All rights reserved.

A gadolinium(III) complex of a carboxylic-phosphorus acid derivative of diethylenetriamine covalently bound to inulin, a potential macromolecular MRI contrast agent.

PubMed

Lebdusková, Petra; Kotek, Jan; Hermann, Petr; Vander Elst, Luce; Muller, Robert N; Lukes, Ivan; Peters, Joop A

2004-01-01

A novel conjugate of a polysaccharide and a Gd(III) chelate with potential as contrast agent for magnetic resonance imaging (MRI) was synthesized. The structure of the chelate was derived from H5DTPA by replacing the central pendant arm by a phosphinic acid functional group, which was covalently bound to the polysaccharide inulin. On the average, each monosaccharide unit of the inulin was attached to approximately one (0.9) chelate moiety. The average molecular weight is 23110 and the average number of Gd3+ ions per molecule is 24. The ligand binds the Gd3+ ion in an octadentate fashion via three nitrogen atoms, four carboxylate oxygen atoms, and one P-O oxygen atom, and its first coordination sphere is completed by a water molecule. This compound shows promising properties for application as a contrast agent for MRI thanks to a favorable residence lifetime of this water molecule (170 ns at 298 K), a relatively long rotational correlation time (866 ps at 298 K), and the presence of two water molecules in the second coordination sphere of the Gd3+ ion. Furthermore, its stability toward transmetalation with Zn(II) is as high as that of the clinically used [Gd(DTPA)(H2O)]2-.

A small MRI contrast agent library of gadolinium(III)-encapsulated supramolecular nanoparticles for improved relaxivity and sensitivity**

PubMed Central

Chen, Kuan-Ju; Wolahan, Stephanie M.; Wang, Hao; Hsu, Chao-Hsiung; Chang, Hsing-Wei; Durazo, Armando; Hwang, Lian-Pin; Garcia, Mitch A.; Jiang, Ziyue Karen; Wu, Lily

2010-01-01

We introduce a new category of nanoparticle-based T1 MRI contrast agents (CAs) by encapsulating paramagnetic chelated gadolinium(III), i.e., Gd3+·DOTA, through supramolecular assembly of molecular building blocks that carry complementary molecular recognition motifs, including adamantane (Ad) and β-cyclodextrin (CD). A small library of Gd3+·DOTA-encapsulated supramolecular nanoparticles (Gd3+·DOTA⊂SNPs) was produced by systematically altering the molecular building block mixing ratios. A broad spectrum of relaxation rates was correlated to the resulting Gd3+·DOTA⊂SNP library. Consequently, an optimal synthetic formulation of Gd3+·DOTA⊂SNPs with an r1 of 17.3 s−1mM−1 (ca. 4-fold higher than clinical Gd3+ chelated complexes at high field strengths) was identified. T1-weighted imaging of Gd3+·DOTA⊂SNPs exhibits an enhanced sensitivity with a contrast-to-noise ratio (C/N ratio) ca. 3.6 times greater than that observed for free Gd3+·DTPA. A Gd3+·DOTA⊂SNPs solution was injected into foot pads of mice, and MRI was employed to monitor dynamic lymphatic drainage of the Gd3+·DOTA⊂SNPs-based CA. We observe an increase in signal intensity of the brachial lymph node in T1-weighted imaging after injecting Gd3+·DOTA⊂SNPs but not after injecting Gd3+·DTPA. The MRI results are supported by ICP-MS analysis ex vivo. These results show that Gd3+·DOTA⊂SNPs not only exhibits enhanced relaxivity and high sensitivity but also can serve as a potential tool for diagnosis of cancer metastasis. PMID:21167594

Gd³⁺ Tethered Gold Nanorods for Combined Magnetic Resonance Imaging and Photo-Thermal Therapy.

PubMed

Pitchaimani, Arunkumar; Duong, Tuyen; Nguyen, Thanh; Maurmann, Leila; Key, Jaehong; Bossmann, Stefan H; Aryal, Santosh

2017-04-01

Near infrared (NIR) mediated photothermal therapy and magnetic resonance imaging (MRI) are promising treatment and imaging modalities in the field of cancer theranostics. Gold nanorods are the first choice of materials for NIR-mediated photothermal therapy due to their strong localized surface plasmon resonance (LSPR) at NIR region. Similarly, gadolinium based MRI contrast agents have an ability to increase the ionic and molecular relaxivity, thereby enhancing the solvent proton relaxation rate resulting in contrast enhancement. Herein, the effort has been made to engineer a dual front theranostic agent with combined photothermal and magnetic resonance imaging capacity using gadolinium tethered gold nanorods (Gd3+-AuNR). NIR-responsive gold nanorods were surface fabricated by means of Au-thiol interaction using a thiolated macrocyclic chelator that chelates Gd3+ ions, and further stabilized by thiolated polyethylene glycol (PEG-SH). The magnetic properties of the Gd3+-AuNR displayed an enhanced r 1 relaxivity of 12.1 mM–1s–1, with higher biological stability, and contrast enhancement in both solution state and in cell pellets. In-vitro (cell-free) and ex-vivo (on pig skin) analysis of the Gd3+-AuNR shows enhanced photothermal properties as equivalent to that of the raw AuNR. Furthermore, Gd3+-AuNR showed competent cellular entry and intracellular distribution as revealed by hyperspectral microscopy. In addition, Gd3+-AuNR also exhibits significant thermal ablation of B16–F10 cells in the presence of NIR. Thus, Gd3+-AuNR features a significant theranostic potential with combined photothermal and imaging modality, suggesting a great potential in anticancer therapy.

Primed Infusion with Delayed Equilibrium of Gd.DTPA for Enhanced Imaging of Small Pulmonary Metastases

PubMed Central

Kalber, Tammy L.; Campbell-Washburn, Adrienne E.; Siow, Bernard M.; Sage, Elizabeth; Price, Anthony N.; Ordidge, Katherine L.; Walker-Samuel, Simon

2013-01-01

Objectives To use primed infusions of the magnetic resonance imaging (MRI) contrast agent Gd.DTPA (Magnevist), to achieve an equilibrium between blood and tissue (eqMRI). This may increase tumor Gd concentrations as a novel cancer imaging methodology for the enhancement of small tumor nodules within the low signal-to-noise background of the lung. Methods A primed infusion with a delay before equilibrium (eqMRI) of the Gd(III) chelator Gd.DTPA, via the intraperitoneal route, was used to evaluate gadolinium tumor enhancement as a function of a bolus injection, which is applied routinely in the clinic, compared to gadolinium maintained at equilibrium. A double gated (respiration and cardiac) spin-echo sequence at 9.4T was used to evaluate whole lungs pre contrast and then at 15 (representative of bolus enhancement), 25 and 35 minutes (representative of eqMRI). This was carried out in two lung metastasis models representative of high and low tumor cell seeding. Lungs containing discrete tumor nodes where inflation fixed and taken for haematoxylin and eosin staining as well as CD34 staining for correlation to MRI. Results We demonstrate that sustained Gd enhancement, afforded by Gd equilibrium, increases the detection of pulmonary metastases compared to bolus enhancement and those tumors which enhance at equilibrium are sub-millimetre in size (<0.7 mm2) with a similar morphology to early bronchoalveolar cell carcinomas. Conclusion As Gd-chelates are routinely used in the clinic for detecting tumors by MRI, this methodology is readily transferable to the clinic and advances MRI as a methodology for the detection of small pulmonary tumors. PMID:23382996

A simple polyol-free synthesis route to Gd2O3 nanoparticles for MRI applications: an experimental and theoretical study

NASA Astrophysics Data System (ADS)

Ahrén, Maria; Selegård, Linnéa; Söderlind, Fredrik; Linares, Mathieu; Kauczor, Joanna; Norman, Patrick; Käll, Per-Olov; Uvdal, Kajsa

2012-08-01

Chelated gadolinium ions, e.g., Gd-DTPA, are today used clinically as contrast agents for magnetic resonance imaging (MRI). An attractive alternative contrast agent is composed of gadolinium oxide nanoparticles as they have shown to provide enhanced contrast and, in principle, more straightforward molecular capping possibilities. In this study, we report a new, simple, and polyol-free way of synthesizing 4-5-nm-sized Gd2O3 nanoparticles at room temperature, with high stability and water solubility. The nanoparticles induce high-proton relaxivity compared to Gd-DTPA showing r 1 and r 2 values almost as high as those for free Gd3+ ions in water. The Gd2O3 nanoparticles are capped with acetate and carbonate groups, as shown with infrared spectroscopy, near-edge X-ray absorption spectroscopy, X-ray photoelectron spectroscopy and combined thermogravimetric and mass spectroscopy analysis. Interpretation of infrared spectroscopy data is corroborated by extensive quantum chemical calculations. This nanomaterial is easily prepared and has promising properties to function as a core in a future contrast agent for MRI.

[Retention of contrast media in the history of radiology : Sequelae of the former use of thorotrast and new challenges].

PubMed

van Kaick, G; Delorme, S

2016-12-01

Detection of gadolinium deposits in patients who have repeatedly been administered intravenous gadolinium chelates have given rise to concern regarding the long-term safety of magnetic resonance imaging (MRI) contrast media. Nevertheless, negative long-term clinical effects have not yet been observed. In some publications parallels have been drawn to the sequelae of thorotrast that was formerly used for arterial angiography. In this article the history of thorotrast use is briefly described and in particular why, despite warnings, this substance was used frequently and worldwide. A brief summary of the results of the German Thorotrast Study revealed that high excess rates were only observed for primary malignant liver tumors after a 15-year or longer latency period and to a lesser degree of leukemias, as well as for severe local complications due to paravascular injections, particularly in the neck region. Based on this historical review, we will venture to take stock of the outcome from the "success story" of this contrast agent.

Gadolinium-Based Contrast Agents for MR Cancer Imaging

PubMed Central

Zhou, Zhuxian; Lu, Zheng-Rong

2013-01-01

Magnetic resonance imaging (MRI) is a clinical imaging modality effective for anatomical and functional imaging of diseased soft tissues, including solid tumors. MRI contrast agents have been routinely used for detecting tumor at an early stage. Gadolinium based contrast agents are the most commonly used contrast agents in clinical MRI. There have been significant efforts to design and develop novel Gd(III) contrast agents with high relaxivity, low toxicity and specific tumor binding. The relaxivity of the Gd(III) contrast agents can be increased by proper chemical modification. The toxicity of Gd(III) contrast agents can be reduced by increasing the agents’ thermodynamic and kinetic stability, as well as optimizing their pharmacokinetic properties. The increasing knowledge in the field of cancer genomics and biology provides an opportunity for designing tumor-specific contrast agents. Various new Gd(III) chelates have been designed and evaluated in animal models for more effective cancer MRI. This review outlines the design and development, physicochemical properties, and in vivo properties of several classes of Gd(III)-based MR contrast agents for tumor imaging. PMID:23047730

Myocardial late gadolinium enhancement in specific cardiomyopathies by cardiovascular magnetic resonance: a preliminary experience.

PubMed

Silva, Caterina; Moon, James C; Elkington, Andrew G; John, Anna S; Mohiaddin, Raad H; Pennell, Dudley J

2007-12-01

Late gadolinium enhancement cardiovascular magnetic resonance (CMR) can visualize myocardial interstitial abnormalities. The aim of this study was to assess whether regions of abnormal myocardium can also be visualized by late enhancement gadolinium CMR in the specific cardiomyopathies. A retrospective review of all referrals for gadolinium CMR with specific cardiomyopathy over 20 months. Nine patients with different specific cardiomyopathies were identified. Late enhancement was demonstrated in all patients, with a mean signal intensity of 390 +/- 220% compared with normal regions. The distribution pattern of late enhancement was unlike the subendocardial late enhancement related to coronary territories found in myocardial infarction. The affected areas included papillary muscles (sarcoid), the mid-myocardium (Anderson-Fabry disease, glycogen storage disease, myocarditis, Becker muscular dystrophy) and the global sub-endocardium (systemic sclerosis, Loeffler's endocarditis, amyloid, Churg-Strauss). Focal myocardial late gadolinium enhancement is found in the specific cardiomyopathies, and the pattern is distinct from that seen in infarction. Further systematic studies are warranted to assess whether the pattern and extent of late enhancement may aid diagnosis and prognostic assessment.

Nanosensors for the Chemical Imaging of Acetylcholine Using Magnetic Resonance Imaging.

PubMed

Luo, Yi; Kim, Eric H; Flask, Chris A; Clark, Heather A

2018-06-06

A suite of imaging tools for detecting specific chemicals in the central nervous system could accelerate the understanding of neural signaling events critical to brain function and disease. Here, we introduce a class of nanoparticle sensors for the highly specific detection of acetylcholine in the living brain using magnetic resonance imaging. The nanosensor is composed of acetylcholine-catalyzing enzymes and pH-sensitive gadolinium contrast agents co-localized onto the surface of polymer nanoparticles, which leads to changes in T 1 relaxation rate (1/ T 1 ). The mechanism of the sensor involves the enzymatic hydrolysis of acetylcholine leading to a localized decrease in pH which is detected by the pH-sensitive gadolinium chelate. The concomitant change in 1/ T 1 in vitro measured a 20% increase from 0 to 10 μM acetylcholine concentration. The applicability of the nanosensors in vivo was demonstrated in the rat medial prefrontal cortex showing distinct changes in 1/ T 1 induced by pharmacological stimuli. The highly specific acetylcholine nanosensor we present here offers a promising strategy for detection of cholinergic neurotransmission and will facilitate our understanding of brain function through chemical imaging.

High performance magneto-fluorescent nanoparticles assembled from terbium and gadolinium 1,3-diketones

PubMed Central

Zairov, Rustem; Mustafina, Asiya; Shamsutdinova, Nataliya; Nizameev, Irek; Moreira, Beatriz; Sudakova, Svetlana; Podyachev, Sergey; Fattakhova, Alfia; Safina, Gulnara; Lundstrom, Ingemar; Gubaidullin, Aidar; Vomiero, Alberto

2017-01-01

Polyelectrolyte-coated nanoparticles consisting of terbium and gadolinium complexes with calix[4]arene tetra-diketone ligand were first synthesized. The antenna effect of the ligand on Tb(III) green luminescence and the presence of water molecules in the coordination sphere of Gd(III) bring strong luminescent and magnetic performance to the core-shell nanoparticles. The size and the core-shell morphology of the colloids were studied using transmission electron microscopy and dynamic light scattering. The correlation between photophysical and magnetic properties of the nanoparticles and their core composition was highlighted. The core composition was optimized for the longitudinal relaxivity to be greater than that of the commercial magnetic resonance imaging (MRI) contrast agents together with high level of Tb(III)-centered luminescence. The tuning of both magnetic and luminescent output of nanoparticles is obtained via the simple variation of lanthanide chelates concentrations in the initial synthetic solution. The exposure of the pheochromocytoma 12 (PC 12) tumor cells and periphery human blood lymphocytes to nanoparticles results in negligible effect on cell viability, decreased platelet aggregation and bright coloring, indicating the nanoparticles as promising candidates for dual magneto-fluorescent bioimaging. PMID:28091590

High performance magneto-fluorescent nanoparticles assembled from terbium and gadolinium 1,3-diketones

NASA Astrophysics Data System (ADS)

Zairov, Rustem; Mustafina, Asiya; Shamsutdinova, Nataliya; Nizameev, Irek; Moreira, Beatriz; Sudakova, Svetlana; Podyachev, Sergey; Fattakhova, Alfia; Safina, Gulnara; Lundstrom, Ingemar; Gubaidullin, Aidar; Vomiero, Alberto

2017-01-01

Polyelectrolyte-coated nanoparticles consisting of terbium and gadolinium complexes with calix[4]arene tetra-diketone ligand were first synthesized. The antenna effect of the ligand on Tb(III) green luminescence and the presence of water molecules in the coordination sphere of Gd(III) bring strong luminescent and magnetic performance to the core-shell nanoparticles. The size and the core-shell morphology of the colloids were studied using transmission electron microscopy and dynamic light scattering. The correlation between photophysical and magnetic properties of the nanoparticles and their core composition was highlighted. The core composition was optimized for the longitudinal relaxivity to be greater than that of the commercial magnetic resonance imaging (MRI) contrast agents together with high level of Tb(III)-centered luminescence. The tuning of both magnetic and luminescent output of nanoparticles is obtained via the simple variation of lanthanide chelates concentrations in the initial synthetic solution. The exposure of the pheochromocytoma 12 (PC 12) tumor cells and periphery human blood lymphocytes to nanoparticles results in negligible effect on cell viability, decreased platelet aggregation and bright coloring, indicating the nanoparticles as promising candidates for dual magneto-fluorescent bioimaging.

Comparison of nephrotoxicity between two gadolinium-contrasts, gadodiamide and gadopentetate in patients with mildly diminished renal failure.

PubMed

Naito, Shokichi; Tazaki, Hiromi; Okamoto, Tomoko; Takeuchi, Kazuhiro; Kan, Shinichi; Takeuchi, Yasuo; Kamata, Kouju

2017-01-01

Although gadolinium (Gd)-based contrast media have been found to be nephrotoxic, their nephrotoxicity, and the dependence of nephrotoxicity on chelate types, have not been assessed in patients with normal or mildly diminished renal failure. This prospective, randomized study compared the nephrotoxicity of low doses of the nonionic Gd-based contrast medium gadodiamide (Omniscan®) and the ionic Gd-based contrast medium gadopentetate (Magnevist®) in patients with serum creatinine < 1.6 mg/dL. Patients aged 20 to 80 years, weighing 45 to 70 kg and with normal or < 1.6 mg/dL Serum-creatinine in the 3 months prior to undergoing magnetic resonance imaging (MRI) of brain, were enrolled. Patients were randomized to receive 0.1 mol/kg gadodiamide or gadopentetate. Serum-creatinine, serum cystatin-C, estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) formula, and estimated creatinine clearance rate (eCCr) using the Cockcroft-Gault formula were measured just before and 16-80 hr after MRI. Groups were compared statistically by Mann-Whitney U-tests and Wilcoxon signed-rank tests. There were no significant differences in clinical characteristics between the gadodiamide (n = 43) and gadopentetate (n = 59) groups. Serum-creatinine, eGFR and eCCr before and 16-80 hr after MRI did not differ significantly within either group or between the two groups. Serum cystatin-C was significantly higher 16-80 hr after than before MRI only in the gadodiamide group (0.79 ± 0.21 vs. 0.74 ± 0.14 mg/L, p = 0.028). The ionic contrast medium, gadopentetate, did not affect renal function during MRI, whereas the nonionic contrast medium, gadodiamide, affected renal function transiently.

Rapid dynamic R1 /R2 */temperature assessment: a method with potential for monitoring drug delivery.

PubMed

Lorenzato, Cyril; Oerlemans, Chris; Cernicanu, Alexandru; Ries, Mario; Denis de Senneville, Baudouin; Moonen, Chrit; Bos, Clemens

2014-11-01

Local drug delivery by hyperthermia-induced drug release from thermosensitive liposomes (TSLs) may reduce the systemic toxicity of chemotherapy, whilst maintaining or increasing its efficacy. Relaxivity contrast agents can be co-encapsulated with the drug to allow the visualization of the presence of liposomes, by means of R2 *, as well as the co-release of the contrast agent and the drug, by means of R1, on heating. Here, the mathematical method used to extract both R2 * and R1 from a fast dynamic multi-echo spoiled gradient echo (ME-SPGR) is presented and analyzed. Finally, this method is used to monitor such release events. R2 * was obtained from a fit to the ME-SPGR data. Absolute R1 was calculated from the signal magnitude changes corrected for the apparent proton density changes and a baseline Look-Locker R1 map. The method was used to monitor nearly homogeneous water bath heating and local focused ultrasound heating of muscle tissue, and to visualize the release of a gadolinium chelate from TSLs in vitro. R2 *, R1 and temperature maps were measured with a 5-s temporal resolution. Both R2 *and R1 measured were found to change with temperature. The dynamic R1 measurements after heating agreed with the Look-Locker R1 values if changes in equilibrium magnetization with temperature were considered. Release of gadolinium from TSLs was detected by an R1 increase near the phase transition temperature, as well as a shallow R2 * increase. Simultaneous temperature, R2 * and R1 mapping is feasible in real time and has the potential for use in image-guided drug delivery studies. Copyright © 2014 John Wiley & Sons, Ltd.

A Manganese Alternative to Gadolinium for MRI Contrast

PubMed Central

Gale, Eric M.; Atanasova, Iliyana P.; Blasi, Francesco; Ay, Ilknur; Caravan, Peter

2016-01-01

Contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI) are routinely used to diagnose soft tissue and vascular abnormalities. However safety concerns limit the use of iodinated and gadolinium- (Gd) based CT and MRI contrast media in renally compromised patients. With an estimated 14% of the US population suffering from chronic kidney disease (CKD), contrast media compatible with renal impairment is sorely needed. We present the new manganese(II) complex [Mn(PyC3A)(H2O)]- as a Gd alternative. [Mn(PyC3A)(H2O)]- is amongst the most stable Mn(II) complexes at pH 7.4 (log KML = 11.40). In the presence of 25 mol equiv. Zn at pH 6.0, 37 °C, [Mn(PyC3A)(H2O)]- is 20-fold more resistant to dissociation than [Gd(DTPA)(H2O)]2-. Relaxivity of [Mn(PyC3A)(H2O)]- in blood plasma is comparable to commercial Gd contrast agents. Biodistribution analysis confirms that [Mn(PyC3A)(H2O)]- clears via a mixed renal/ hepatobiliary pathway with >99% elimination by 24h. [Mn(PyC3A)(H2O)]- was modified to form a bifunctional chelator and 4 chelates were conjugated to a fibrin-specific peptide to give Mn-FBP. Mn-FBP binds the soluble fibrin fragment DD(E) with Kd = 110 nM. Per Mn relaxivity of Mn-FBP is 4-fold greater than [Mn(PyC3A)(H2O)]- and increases 60% in the presence of fibrin, consistent with binding. Mn-FBP provided equivalent thrombus enhancement to the state of the art Gd analog, EP-2104R, in a rat model of arterial thrombosis. Mn metabolite analysis reveals no evidence of dechelation and the probe was >99% eliminated after 24 hr. [Mn(PyC3A)(H2O)]- is a lead development candidate for an imaging probe that is compatible with renally compromised patients. PMID:26588204

Quantitative structure-property relationship (correlation analysis) of phosphonic acid-based chelates in design of MRI contrast agent.

PubMed

Tiwari, Anjani K; Ojha, Himanshu; Kaul, Ankur; Dutta, Anupama; Srivastava, Pooja; Shukla, Gauri; Srivastava, Rakesh; Mishra, Anil K

2009-07-01

Nuclear magnetic resonance imaging is a very useful tool in modern medical diagnostics, especially when gadolinium (III)-based contrast agents are administered to the patient with the aim of increasing the image contrast between normal and diseased tissues. With the use of soft modelling techniques such as quantitative structure-activity relationship/quantitative structure-property relationship after a suitable description of their molecular structure, we have studied a series of phosphonic acid for designing new MRI contrast agent. Quantitative structure-property relationship studies with multiple linear regression analysis were applied to find correlation between different calculated molecular descriptors of the phosphonic acid-based chelating agent and their stability constants. The final quantitative structure-property relationship mathematical models were found as--quantitative structure-property relationship Model for phosphonic acid series (Model 1)--log K(ML) = {5.00243(+/-0.7102)}- MR {0.0263(+/-0.540)}n = 12 l r l = 0.942 s = 0.183 F = 99.165 quantitative structure-property relationship Model for phosphonic acid series (Model 2)--log K(ML) = {5.06280(+/-0.3418)}- MR {0.0252(+/- .198)}n = 12 l r l = 0.956 s = 0.186 F = 99.256.

Use of a Genetically Engineered Protein for the Design of a Multivalent MRI Contrast Agent

PubMed Central

Karfeld, Lindsay S.; Bull, Steve R.; Davis, Nicolynn E.; Meade, Thomas J.; Barron, Annelise E.

2008-01-01

The majority of clinically used contrast agents (CAs) for magnetic resonance imaging have low relaxivities and thus require high concentrations for signal enhancement. Research has turned to multivalent, macromolecular CAs to increase CA efficiency. However, previously developed macromolecular CAs do not provide high relaxivities, have limited biocompatibility, and/or do not have a structure that is readily modifiable to tailor to particular applications. We report a new family of multivalent, biomacromolecular, genetically engineered protein polymer-based CAs; the protein backbone contains evenly spaced lysines that are derivatized with gadolinium (Gd(III)) chelators. The protein's length and repeating amino acid sequence are genetically specified. We reproducibly obtained conjugates with an average of 8 – 9 Gd(III) chelators per protein. These multivalent CAs reproducibly provide a high relaxivity of 7.3 mM-1s-1 per Gd(III) and 62.6 mM-1s-1 per molecule. Furthermore, they can be incorporated into biomaterial hydrogels via chemical crosslinking of remaining free lysines, and provide a dramatic contrast enhancement. Thus, these protein polymer CAs could be a useful tool for following the evolution of tissue engineering scaffolds. PMID:17927227

Magnetic resonance imaging for the in vivo evaluation of gastric-retentive tablets.

PubMed

Steingoetter, Andreas; Weishaupt, Dominik; Kunz, Patrick; Mäder, Karsten; Lengsfeld, Hans; Thumshirn, Miriam; Boesiger, Peter; Fried, Michael; Schwizer, Werner

2003-12-01

To develop a magnetic resonance imaging (MRI) technique for assessing in vivo properties of orally ingested gastric-retentive tablets under physiologic conditions. Tablets with different floating characteristics (tablet A-C) were marked with superparamagnetic Fe3O4 particles to analyze intragastric tablet position and residence time in human volunteers. Optimal Fe3O4 concentration was determined in vitro. Intragastric release characteristic of one slow-release tablet (tablet D) was analyzed by embedding gadolinium chelates (Gd-DOTA) as a drug model into the tablet. All volunteers underwent MRI in the sitting position. Tablet performance was analyzed in terms of relative position of tablet to intragastric meal level (with 100% at meal surface), intragastric residence time (min) and Gd-DOTA distribution volume (% of meal volume). Intragastric tablet floating performance and residence time of tablets (tablet A-D) as well as the intragastric Gd-DOTA distribution of tablet D could be monitored using MRI. Tablet floating performance was different between the tablets (A, 93%(95 - 9%); B, 80%(80 - 68%): C, 38%(63 - 32%); p < 0.05). The intragastric distribution volume of Gd-DOTA was 19.9% proximally and 35.5% distally. The use of MRI allows the assessment of galenic properties of orally ingested tablets in humans in seated position.

Preparation and Evaluation of Multiple Nanoemulsions Containing Gadolinium (III) Chelate as a Potential Magnetic Resonance Imaging (MRI) Contrast Agent.

PubMed

Sigward, Estelle; Corvis, Yohann; Doan, Bich-Thuy; Kindsiko, Kadri; Seguin, Johanne; Scherman, Daniel; Brossard, Denis; Mignet, Nathalie; Espeau, Philippe; Crauste-Manciet, Sylvie

2015-09-01

The objective was to develop, characterize and assess the potentiality of W1/O/W2 self-emulsifying multiple nanoemulsions to enhance signal/noise ratio for Magnetic Resonance Imaging (MRI). For this purpose, a new formulation, was designed for encapsulation efficiency and stability. Various methods were used to characterize encapsulation efficiency ,in particular calorimetric methods (Differential Scanning Calorimetry (DSC), thermogravimetry analysis) and ultrafiltration. MRI in vitro relaxivities were assessed on loaded DTPA-Gd multiple nanoemulsions. Characterization of the formulation, in particular of encapsulation efficiency was a challenge due to interactions found with ultrafiltration method. Thanks to the specifically developed DSC protocol, we were able to confirm the formation of multiple nanoemulsions, differentiate loaded from unloaded nanoemulsions and measure the encapsulation efficiency which was found to be quite high with a 68% of drug loaded. Relaxivity studies showed that the self-emulsifying W/O/W nanoemulsions were positive contrast agents, exhibiting higher relaxivities than those of the DTPA-Gd solution taken as a reference. New self-emulsifying multiple nanoemulsions that were able to load satisfactory amounts of contrasting agent were successfully developed as potential MRI contrasting agents. A specific DSC protocol was needed to be developed to characterize these complex systems as it would be useful to develop these self-formation formulations.

Magnetic resonance conditional paramagnetic choke for suppression of imaging artifacts during magnetic resonance imaging.

PubMed

Wu, Kevin J; Gregory, T Stan; Boland, Brian L; Zhao, Wujun; Cheng, Rui; Mao, Leidong; Tse, Zion Tsz Ho

2018-06-01

Higher risk patient populations require continuous physiological monitoring and, in some cases, connected life-support systems, during magnetic resonance imaging examinations. While recently there has been a shift toward wireless technology, some of the magnetic resonance imaging devices are still connected to the outside using cabling that could interfere with the magnetic resonance imaging's radio frequency during scanning, resulting in excessive heating. We developed a passive method for radio frequency suppression on cabling that may assist in making some of these devices magnetic resonance imaging compatible. A barrel-shaped strongly paramagnetic choke was developed to suppress induced radio frequency signals which are overlaid onto physiological monitoring leads during magnetic resonance imaging. It utilized a choke placed along the signal lines, with a gadolinium solution core. The choke's magnetic susceptibility was modeled, for a given geometric design, at increasing chelate concentration levels, and measured using a vibrating sample magnetometer. Radio frequency noise suppression versus frequency was quantified with network-analyzer measurements and tested using cabling placed in the magnetic resonance imaging scanner. Temperature-elevation and image-quality reduction due to the device were measured using American Society for Testing and Materials phantoms. Prototype chokes with gadolinium solution cores exhibited increasing magnetic susceptibility, and insertion loss (S21) also showed higher attenuation as gadolinium concentration increased. Image artifacts extending <4 mm from the choke were observed during magnetic resonance imaging, which agreed well with the predicted ∼3 mm artifact from the electrochemical machining simulation. An accompanying temperature increase of <1 °C was observed in the magnetic resonance imaging phantom trial. An effective paramagnetic choke for radio frequency suppression during magnetic resonance imaging was developed and its performance demonstrated.

Chelation therapy after the Trial to Assess Chelation Therapy: results of a unique trial

PubMed Central

Avila, Maria D.; Escolar, Esteban; Lamas, Gervasio A.

2014-01-01

Purpose of review EDTA chelation therapy has been in off-label use for the treatment of atherosclerosis. We review the results of the first large-scale randomized trial of this treatment. Recent findings The trial to assess chelation therapy was a $30 million National Institutes of Health-funded study of the safety and efficacy of EDTA-based chelation infusions in 1708 post-myocardial infarction (MI) patients. The trial to assess chelation therapy demonstrated a significant (P = 0.035) 18% reduction in a combined primary endpoint of death, MI, stroke, coronary revascularization, or hospitalization for angina. In diabetic patients the benefit was more extreme, with a 41% relative reduction in risk (P = 0.0002) and a 43% reduction in total mortality (P = 0.011). Safety data were favorable. A reduction of oxidative stress by chelation of toxic metals has been proposed as a possible mechanism of action. Summary Recent research suggests that EDTA chelation may be a well-tolerated and effective treatment for post-MI patients. Future replication and mechanistic studies are important prior to implementation in all post-MI patients. PMID:25023079

Technical aspects of MRI signal change quantification after gadolinium-based contrast agents' administration.

PubMed

Ramalho, Joana; Ramalho, Miguel; AlObaidy, Mamdoh; Semelka, Richard C

2016-12-01

Over the last 2years several studies have been published regarding gadolinium deposition in brain structures in patients with normal renal function after repeated administrations of gadolinium-based contrast agents (GBCAs). Most of the publications are magnetic resonance imaging (MRI) based retrospective studies, where gadolinium deposition may be indirectly measured by evaluating changes in T1 signal intensity (SI) in brain tissue, particularly in the dentate nucleus (DN) and/or globus pallidi (GP). The direct correlation between T1 signal changes and gadolinium deposition was validated by human pathology studies. However, the variability of the MR equipment and parameters used across different publications, along with the inherent limitations of MRI to assess gadolinium in human tissues should be acknowledged when interpreting those studies. Nevertheless, MRI studies remain essential regarding gadolinium bio-distribution knowledge. The aim of this paper is to overview current knowledge of technical aspects of T1 signal intensity evaluation by MRI and describe confounding factors, with the intention to achieve higher accuracy and maximize reproducibility. Copyright © 2016 Elsevier Inc. All rights reserved.

Proton Relaxivity and Magnetic Hyperthermia Evaluation of Gadolinium Doped Nickel Ferrite Nanoparticles as Potential Theranostic Agents.

PubMed

Yadavalli, Tejabhiram; Raja, Paradeep; Ramaswamy, Shivaraman; Chandrasekharan, Gopalakrishnan; Chennakesavulu, Ramasamy

2017-02-01

This paper outlines the preparation of gadolinium doped nickel ferrite nanoparticles as potential magnetic carriers and longitudinal magnetic resonance imaging contrast agents using hydrothermal method with gadolinium concentration varying from 10% to 40%. A concise effect on the crystal structure was observed at 10% and 20% gadolinium doping, while gadolinium oxide was observed to leach at concentrations exceeding 20%. Further, gadolinium doped nickel ferrites were analyzed for their morphological, magnetic, proton relaxation and magnetic hyperthermia heating properties to understand their potential role as magnetic carrier agents. Low temperature and room temperature magnetic studies conducted on the samples showed comparatively high magnetic saturation with low remanent magnetization. Further, relaxometry studies revealed a high relaxation rate of 6.63 s−1 at a concentration of 0.1 mg/mL. Magnetic hyperthermia studies of the samples at a concentration of 1 mg/mL, assessed that the samples attained a temperature of 68 °C in 240 seconds.

Investigation of a potential macromolecular MRI contrast agent prepared from PPI (G = 2, polypropyleneimine, generation 2) dendrimer bifunctional chelates

NASA Astrophysics Data System (ADS)

Wang, Jianxin Steven

The long-term objective is to develop magnetic resonance (MR) contrast agents that actively and passively target tumors for diagnosis and therapy. Many diagnostic imaging techniques for cancer lack specificity. A dendrimer based magnetic resonance imaging contrast agent has been developed with large proton relaxation enhancements and high molecular relaxivities. A new type of linear dendrimer based MRI contrast agent that is built from the polypropyleneimine and polyamidoamine dendrimers in which free amines have been conjugated to the chelate DTPA, which further formed the complex with Gadolinium (Gd) was studied. The specific research goals were to test the hypothesis that a linear chelate with macromolecular agents can be used in vitro and in vivo. This work successfully examined the adequacy and viability of the application for this agent in vitro and in vivo. A small animal whole body counter was designed and constructed to allow us to monitor biodistribution and kinetic mechanisms using a radioisotope labeled complex. The procedures of metal labeling, separation and purification have been established from this work. A biodistribution study has been performed using radioisotope induced organ/tissue counting and gamma camera imaging. The ratio of percentage of injected dose per gram organ/tissue for kidney and liver is 3.71 from whole body counter and 3.77 from the gamma camera. The results suggested that retention of Gd (III) is too high and a more kinetically stable chelate should be developed. The pharmacokinetic was evaluated in the whole animal model with the whole body clearance, and a kinetics model was developed. The pharmacokinetic results showed a bi-exponential decay in the animal model with two component excretion constants 1.43e(-5) and 0.0038511, which give half-lives of 3 hours and 33.6 days, respectively. Magnetic resonance imaging of this complex resulted in a 52% contrast enhancement in the rat kidney following the agents' administration in vivo.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lakshminarayan, Raghuram, E-mail: raghuram.lakshminarayan@hey.nhs.u; Simpson, James O.; Ettles, Duncan F., E-mail: Duncan.Ettles@hey.nhs.u

Magnetic resonance angiography (MRA) has become an established imaging modality in the management of lower-limb arterial disease, with emerging roles in treatment planning and follow-up. Contrast-enhanced MRA is now the most widely used technique with clinically acceptable results in the majority of patients. Difficulties in imaging and image interpretation are recognised in certain subgroups, including patients with critical limb ischaemia as well as patients with stents. Although newer contrast agents and refined imaging protocols may offer some solutions to these problems, this optimism is balanced by concerns about the toxicity of certain gadolinium chelates. Further development of interventional MRA remainsmore » one of the most significant challenges in the development of magnetic resonance imaging-guided peripheral vascular intervention. The status of MRA in managing patients with lower-limb arterial disease in current clinical practice is reviewed.« less

Yeast respond to hypotonic shock with a calcium pulse

NASA Technical Reports Server (NTRS)

Batiza, A. F.; Schulz, T.; Masson, P. H.

1996-01-01

We have used the transgenic AEQUORIN calcium reporter system to monitor the cytosolic calcium ([Ca2+]cyt) response of Saccharomyces cerevisiae to hypotonic shock. Such a shock generates an almost immediate and transient rise in [Ca2+]cyt which is eliminated by gadolinium, a blocker of stretch-activated channels. In addition, this transient rise in [Ca2+]cyt is initially insensitive to 1,2-bis-(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA), an extracellular calcium chelator. However, BAPTA abruptly attenuates the maintenance of that transient rise. These data show that hypotonic shock generates a stretch-activated channel-dependent calcium pulse in yeast. They also suggest that the immediate calcium influx is primarily generated from intracellular stores, and that a sustained increase in [Ca2+]cyt depends upon extracellular calcium.

Feasibility and accuracy of dual-layer spectral detector computed tomography for quantification of gadolinium: a phantom study.

PubMed

van Hamersvelt, Robbert W; Willemink, Martin J; de Jong, Pim A; Milles, Julien; Vlassenbroek, Alain; Schilham, Arnold M R; Leiner, Tim

2017-09-01

The aim of this study was to evaluate the feasibility and accuracy of dual-layer spectral detector CT (SDCT) for the quantification of clinically encountered gadolinium concentrations. The cardiac chamber of an anthropomorphic thoracic phantom was equipped with 14 tubular inserts containing different gadolinium concentrations, ranging from 0 to 26.3 mg/mL (0.0, 0.1, 0.2, 0.4, 0.5, 1.0, 2.0, 3.0, 4.0, 5.1, 10.6, 15.7, 20.7 and 26.3 mg/mL). Images were acquired using a novel 64-detector row SDCT system at 120 and 140 kVp. Acquisitions were repeated five times to assess reproducibility. Regions of interest (ROIs) were drawn on three slices per insert. A spectral plot was extracted for every ROI and mean attenuation profiles were fitted to known attenuation profiles of water and pure gadolinium using in-house-developed software to calculate gadolinium concentrations. At both 120 and 140 kVp, excellent correlations between scan repetitions and true and measured gadolinium concentrations were found (R > 0.99, P < 0.001; ICCs > 0.99, CI 0.99-1.00). Relative mean measurement errors stayed below 10% down to 2.0 mg/mL true gadolinium concentration at 120 kVp and below 5% down to 1.0 mg/mL true gadolinium concentration at 140 kVp. SDCT allows for accurate quantification of gadolinium at both 120 and 140 kVp. Lowest measurement errors were found for 140 kVp acquisitions. • Gadolinium quantification may be useful in patients with contraindication to iodine. • Dual-layer spectral detector CT allows for overall accurate quantification of gadolinium. • Interscan variability of gadolinium quantification using SDCT material decomposition is excellent.

The dosimetric impact of gadolinium-based contrast media in GBM brain patient plans for a MRI-Linac

NASA Astrophysics Data System (ADS)

Bilal Ahmad, Syed; Paudel, Moti Raj; Sarfehnia, Arman; Kim, Anthony; Pang, Geordi; Ruschin, Mark; Sahgal, Arjun; Keller, Brian M.

2017-08-01

Dosimetric effects of gadolinium based contrast media (Gadovist) were evaluated for the Elekta MRI linear accelerator using the research version of the Monaco treatment planning system (TPS). In order to represent a gadolinium uptake, the contrast was manually assigned to a phantom as well as to the gross tumour volume (GTV) of 6 glioblastoma multiforme (GBM) patients. A preliminary estimate of the dose enhancement, due to gadolinium, was performed using the phantom irradiated with a single beam. A more complicated assessment was performed for the GBM patients using a 7 field IMRT technique. The material table in Monaco was modified in order to identify the presence of a non-biological material. The dose distribution was modelled using GPUMCD (MC algorithm in Monaco) for an unmodified (or default) material table (DMT) as well as for a modified (or custom) material table (CMT) for both the phantom and patients. Various concentrations ranging between 8 and 157 mg ml-1 were used to represent the gadolinium uptake in the patient’s GTV. It was assumed that the gadolinium concentration remained the same for the entire course of radiation treatment. Results showed that at the tissue-Gadovist interface, inside the phantom, dose scored using the DMT was 7% lower compared to that using the CMT for 157 mg ml-1 concentration of gadolinium. Dosimetric differences in the case of the patient study were measured using the DVH parameters. D 50% was higher by 6% when the DMT was used compared to the CMT for dose modelling for a gadolinium concentration of 157 mg ml-1. This difference decreased gradually with decreasing concentration of gadolinium. It was concluded that dosimetric differences can be quantified in Monaco if the tumour-gadolinium concentration is more than 23 mg ml-1. If the gadolinium concentration is lower than 23 mg ml-1, then a correction for the presence of gadolinium may not be necessary in the TPS.

The dosimetric impact of gadolinium-based contrast media in GBM brain patient plans for a MRI-Linac.

PubMed

Ahmad, Syed Bilal; Paudel, Moti Raj; Sarfehnia, Arman; Kim, Anthony; Pang, Geordi; Ruschin, Mark; Sahgal, Arjun; Keller, Brian M

2017-08-01

Dosimetric effects of gadolinium based contrast media (Gadovist) were evaluated for the Elekta MRI linear accelerator using the research version of the Monaco treatment planning system (TPS). In order to represent a gadolinium uptake, the contrast was manually assigned to a phantom as well as to the gross tumour volume (GTV) of 6 glioblastoma multiforme (GBM) patients. A preliminary estimate of the dose enhancement, due to gadolinium, was performed using the phantom irradiated with a single beam. A more complicated assessment was performed for the GBM patients using a 7 field IMRT technique. The material table in Monaco was modified in order to identify the presence of a non-biological material. The dose distribution was modelled using GPUMCD (MC algorithm in Monaco) for an unmodified (or default) material table (DMT) as well as for a modified (or custom) material table (CMT) for both the phantom and patients. Various concentrations ranging between 8 and 157 mg ml -1 were used to represent the gadolinium uptake in the patient's GTV. It was assumed that the gadolinium concentration remained the same for the entire course of radiation treatment. Results showed that at the tissue-Gadovist interface, inside the phantom, dose scored using the DMT was 7% lower compared to that using the CMT for 157 mg ml -1 concentration of gadolinium. Dosimetric differences in the case of the patient study were measured using the DVH parameters. D 50% was higher by 6% when the DMT was used compared to the CMT for dose modelling for a gadolinium concentration of 157 mg ml -1 . This difference decreased gradually with decreasing concentration of gadolinium. It was concluded that dosimetric differences can be quantified in Monaco if the tumour-gadolinium concentration is more than 23 mg ml -1 . If the gadolinium concentration is lower than 23 mg ml -1 , then a correction for the presence of gadolinium may not be necessary in the TPS.

Chelation therapy to treat atherosclerosis, particularly in diabetes: Is it time to reconsider?

PubMed Central

Lamas, Gervasio A; Ergui, Ian

2016-01-01

Summary Reports and case series have suggested a possible beneficial effect of chelation therapy in patients with atherosclerotic disease. Small randomized trials conducted in patients with angina or peripheral artery disease, however, were not sufficiently powered to provide conclusive evidence on clinical outcomes. The Trial to Assess Chelation Therapy (TACT) was the first randomized trial adequately powered to detect the effects of chelation therapy on clinical endpoints. Chelation reduced adverse cardiovascular events in a post myocardial infarction (MI) population. Patients with diabetes demonstrated even greater benefit, with a number needed to treat of 6.5 patients to prevent a cardiac event over 5 years. These results led to the revision of the ACC/AHA guideline recommendations for chelation therapy, changing its classification from class III to class IIb. TACT2, a replicative trial, will assess the effects of chelation therapy on cardiovascular outcomes in diabetic patients with a prior myocardial infarction. PMID:27149141

Lipid-derived free radical production in superantigen-induced interstitial pneumonia

PubMed Central

Miyakawa, Hisako; Mason, Ronald P.; Jiang, JinJie; Kadiiska, Maria B.

2009-01-01

We studied the free radical generation involved in the development of interstitial pneumonia (IP) in an animal model of autoimmune disease. We observed an electron spin resonance (ESR) spectrum of α-(4-pyridyl-1-oxide)-N-tert-butylnitrone (POBN) radical adducts detected in the lipid extract of lungs in autoimmune-prone mice after intratracheal instillation of staphylococcal enterotoxin B. The POBN adducts detected by ESR were paralleled by infiltration of macrophages and neutrophils in the bronchoalveolar lavage fluid. To further investigate the mechanism of free radical generation, mice were pretreated with the macrophage toxicant gadolinium chloride, which significantly suppressed the radical generation. Free radical generation was also decreased by pretreatment with the xanthine oxidase (XO) inhibitor allopurinol, the iron chelator Desferal, and the inducible nitric oxide synthase (iNOS) inhibitor 1400W. Histopathologically, these drugs significantly reduced both the cell infiltration to alveolar septal walls and the synthesis of pulmonary collagen fibers. Experiments with NADPH oxidase knockout mice showed that NADPH oxidase did not contribute to lipid radical generation. These results suggest that lipid-derived carbon-centered free radical production is important in the manifestation of IP and that a macrophage toxicant, an XO inhibitor, an iron chelator, and an iNOS inhibitor protect against both radical generation and the manifestation of IP. PMID:19376221

Gd(III) complexes for electron-electron dipolar spectroscopy: Effects of deuteration, pH and zero field splitting.

PubMed

Garbuio, Luca; Zimmermann, Kaspar; Häussinger, Daniel; Yulikov, Maxim

2015-10-01

Spectral parameters of Gd(III) complexes are intimately linked to the performance of the Gd(III)-nitroxide or Gd(III)-Gd(III) double electron-electron resonance (DEER or PELDOR) techniques, as well as to that of relaxation induced dipolar modulation enhancement (RIDME) spectroscopy with Gd(III) ions. These techniques are of interest for applications in structural biology, since they can selectively detect site-to-site distances in biomolecules or biomolecular complexes in the nanometer range. Here we report relaxation properties, echo detected EPR spectra, as well as the magnitude of the echo reduction effect in Gd(III)-nitroxide DEER for a series of Gadolinium(III) complexes with chelating agents derived from tetraazacyclododecane. We observed that solvent deuteration does not only lengthen the relaxation times of Gd(III) centers but also weakens the DEER echo reduction effect. Both of these phenomena lead to an improved signal-to-noise ratios or, alternatively, longer accessible distance range in pulse EPR measurements. The presented data enrich the knowledge on paramagnetic Gd(III) chelate complexes in frozen solutions, and can help optimize the experimental conditions for most types of the pulse measurements of the electron-electron dipolar interactions. Copyright © 2015 Elsevier Inc. All rights reserved.

Cardiovascular Magnetic Resonance and prognosis in cardiac amyloidosis

PubMed Central

Maceira, Alicia M; Prasad, Sanjay K; Hawkins, Philip N; Roughton, Michael; Pennell, Dudley J

2008-01-01

Background Cardiac involvement is common in amyloidosis and associated with a variably adverse outcome. We have previously shown that cardiovascular magnetic resonance (CMR) can assess deposition of amyloid protein in the myocardial interstitium. In this study we assessed the prognostic value of late gadolinium enhancement (LGE) and gadolinium kinetics in cardiac amyloidosis in a prospective longitudinal study. Materials and methods The pre-defined study end point was all-cause mortality. We prospectively followed a cohort of 29 patients with proven cardiac amyloidosis. All patients underwent biopsy, 2D-echocardiography and Doppler studies, 123I-SAP scintigraphy, serum NT pro BNP assay, and CMR with a T1 mapping method and late gadolinium enhancement (LGE). Results Patients with were followed for a median of 623 days (IQ range 221, 1436), during which 17 (58%) patients died. The presence of myocardial LGE by itself was not a significant predictor of mortality. However, death was predicted by gadolinium kinetics, with the 2 minute post-gadolinium intramyocardial T1 difference between subepicardium and subendocardium predicting mortality with 85% accuracy at a threshold value of 23 ms (the lower the difference the worse the prognosis). Intramyocardial T1 gradient was a better predictor of survival than FLC response to chemotherapy (Kaplan Meier analysis P = 0.049) or diastolic function (Kaplan-Meier analysis P = 0.205). Conclusion In cardiac amyloidosis, CMR provides unique information relating to risk of mortality based on gadolinium kinetics which reflects the severity of the cardiac amyloid burden. PMID:19032744

WE-FG-BRA-07: Theranostic Nanoparticles Improve Clinical MR-Guided Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Detappe, A; Institut Lumiere-Matiere, Lyon, FR; Kunjachan, S

Purpose: MR-guided radiation therapy is a current and emerging clinical reality. We have designed and tested a silica-based gadolinium chelates nanoparticle (AGuIX) for integration with MR-guided radiation therapy. The AGuIX nanoparticles used in this study are a dual-modality probe with radiosensitization properties and better MRI contrast than current FDA-approved gadolinium chelates. In advance of an approved Phase I clinical trial, we report on the efficacy and safety in multiple animal models and clinically relevant radiation conditions. By modeling our study on current clinic workflows, we show compatibility with modern patient care, thus heightening the translational significance of this research. Methods:more » The dual imaging and therapy functionality of AGuIX was investigated in mice with clinical radiation beams while safety was evaluated in mice, and nonhuman primates after systemic injection of 0.25 mg/g of nanoparticles. MRI/ICP-MS were used to measure tumor uptake and biodistribution. Due to their small size (2–3 nm), AGuIX have good renal clearance (t1/2=19min). We performed in vitro cell uptake quantification and radiosensitization studies (clonogenic assays and DNA damage quantification). In vivo radiation therapy studies were performed with both 6MV and 6MV-FFF clinical radiation beams. Histology was performed to measure the increase in DNA damage in the tumor and to evaluate the toxicity in healthy tissues. Results: In vitro and in vivo results demonstrate statistically significant increase (P < 0.01) in DNA damage, tumor growth supression and survival (+100 days) compared to radiation alone. Negligible toxicity was observed in all of the animal models. The combination of 6MV-FFF/AGuIX demonstrated a substantial dose enhancement compared to 6MV/AGuIX (DEF = 1.36 vs. 1.22) due to the higher proportion of low energy photons. Conclusion: With demonstrated efficacy and negligible toxicity in mice and non-human primates, AGuIX is a biocompatible nanoplatform with strong translational potential for MR-guided radiation therapy.« less

Do we need gadolinium-based contrast medium for brain magnetic resonance imaging in children?

PubMed

Dünger, Dennis; Krause, Matthias; Gräfe, Daniel; Merkenschlager, Andreas; Roth, Christian; Sorge, Ina

2018-06-01

Brain imaging is the most common examination in pediatric magnetic resonance imaging (MRI), often combined with the use of a gadolinium-based contrast medium. The application of gadolinium-based contrast medium poses some risk. There is limited evidence of the benefits of contrast medium in pediatric brain imaging. To assess the diagnostic gain of contrast-enhanced sequences in brain MRI when the unenhanced sequences are normal. We retrospectively assessed 6,683 brain MR examinations using contrast medium in children younger than 16 years in the pediatric radiology department of the University Hospital Leipzig to determine whether contrast-enhanced sequences delivered additional, clinically relevant information to pre-contrast sequences. All examinations were executed using a 1.5-T or a 3-T system. In 8 of 3,003 (95% confidence interval 0.12-0.52%) unenhanced normal brain examinations, a relevant additional finding was detected when contrast medium was administered. Contrast enhancement led to a change in diagnosis in only one of these cases. Children with a normal pre-contrast brain MRI rarely benefit from contrast medium application. Comparing these results to the risks and disadvantages of a routine gadolinium application, there is substantiated numerical evidence for avoiding routine administration of gadolinium in a pre-contrast normal MRI examination.

Cardiac phenotyping in ex vivo murine embryos using microMRI.

PubMed

Cleary, Jon O; Price, Anthony N; Thomas, David L; Scambler, Peter J; Kyriakopoulou, Vanessa; McCue, Karen; Schneider, Jürgen E; Ordidge, Roger J; Lythgoe, Mark F

2009-10-01

Microscopic MRI (microMRI) is an emerging technique for high-throughput phenotyping of transgenic mouse embryos, and is capable of visualising abnormalities in cardiac development. To identify cardiac defects in embryos, we have optimised embryo preparation and MR acquisition parameters to maximise image quality and assess the phenotypic changes in chromodomain helicase DNA-binding protein 7 (Chd7) transgenic mice. microMRI methods rely on tissue penetration with a gadolinium chelate contrast agent to reduce tissue T(1), thus improving signal-to-noise ratio (SNR) in rapid gradient echo sequences. We investigated 15.5 days post coitum (dpc) wild-type CD-1 embryos fixed in gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA) solutions for either 3 days (2 and 4 mM) or 2 weeks (2, 4, 8 and 16 mM). To assess penetration of the contrast agent into heart tissue and enable image contrast simulations, T(1) and T(*) (2) were measured in heart and background agarose. Compared to 3-day, 2-week fixation showed reduced mean T(1) in the heart at both 2 and 4 mM concentrations (p < 0.0001), resulting in calculated signal gains of 23% (2 mM) and 29% (4 mM). Using T(1) and T(*) (2) values from 2-week concentrations, computer simulation of heart and background signal, and ex vivo 3D gradient echo imaging, we demonstrated that 2-week fixed embryos in 8 mM Gd-DTPA in combination with optimised parameters (TE/TR/alpha/number of averages: 9 ms/20 ms/60 degrees /7) produced the largest SNR in the heart (23.2 +/- 1.0) and heart chamber contrast-to-noise ratio (CNR) (27.1 +/- 1.6). These optimised parameters were then applied to an MRI screen of embryos heterozygous for the gene Chd7, implicated in coloboma of the eye, heart defects, atresia of the choanae, retardation of growth, genital/urinary abnormalities, ear abnormalities and deafness (CHARGE) syndrome (a condition partly characterised by cardiovascular birth defects in humans). A ventricular septal defect was readily identified in the screen, consistent with the human phenotype. (c) 2009 John Wiley & Sons, Ltd.

Poly(acrylic acid) Bridged Gadolinium Metal-Organic Framework-Gold Nanoparticle Composites as Contrast Agents for Computed Tomography and Magnetic Resonance Bimodal Imaging.

PubMed

Tian, Chixia; Zhu, Liping; Lin, Feng; Boyes, Stephen G

2015-08-19

Imaging contrast agents for magnetic resonance imaging (MRI) and computed tomography (CT) have received significant attention in the development of techniques for early stage cancer diagnosis. Gadolinium (Gd)(III), which has seven unpaired electrons and a large magnetic moment, can dramatically influence the water proton relaxation and hence exhibits excellent MRI contrast. On the other hand, gold (Au), which has a high atomic number and high X-ray attenuation coefficient, is an ideal contrast agent candidate for X-ray-based CT imaging. Gd metal-organic framework (MOF) nanoparticles with tunable size, high Gd(III) loading and multivalency can potentially overcome the limitations of clinically utilized Gd chelate contrast agents. In this work, we report for the first time the integration of GdMOF nanoparticles with gold nanoparticles (AuNPs) for the preparation of a MRI/CT bimodal imaging agent. Highly stable hybrid GdMOF/AuNPs composites have been prepared by using poly(acrylic acid) as a bridge between the GdMOF nanoparticles and AuNPs. The hybrid nanocomposites were then evaluated in MRI and CT imaging. The results revealed high longitudinal relaxivity in MRI and excellent CT imaging performance. Therefore, these GdMOF/AuNPs hybrid nanocomposites potentially provide a new platform for the development of multimodal imaging probes.

Poly(acrylic acid) Bridged Gadolinium Metal-Organic Framework-Gold Nanoparticle Composites as Contrast Agents for Computed Tomography and Magnetic Resonance Bimodal Imaging

PubMed Central

Tian, Chixia; Zhu, Liping; Lin, Feng; Boyes, Stephen G.

2015-01-01

Imaging contrast agents for magnetic resonance imaging (MRI) and computed tomography (CT) have received significant attention in the development of techniques for early-stage cancer diagnosis. Gadolinium (Gd) (III), which has seven unpaired electrons and a large magnetic moment, can dramatically influence the water proton relaxation and hence exhibits excellent MRI contrast. On the other hand, gold (Au), which has a high atomic number and high x-ray attenuation coefficient, is an ideal contrast agent candidate for x-ray based CT imaging. Gd metal organic framework (MOF) nanoparticles with tunable size, high Gd (III) loading and multivalency can potentially overcome the limitations of clinically utilized Gd chelate contrast agents. In this work, we report for the first time the integration of GdMOF nanoparticles with gold nanoparticles (AuNPs) for the preparation of a MRI/CT bimodal imaging agent. Highly stable hybrid GdMOF/AuNPs composites have been prepared by using poly(acrylic acid) as a bridge between the GdMOF nanoparticles and AuNPs. The hybrid nanocomposites were then evaluated in MRI and CT imaging. The results revealed high longitudinal relaxivity in MRI and excellent CT imaging performance. Therefore, these GdMOF/AuNPs hybrid nanocomposites potentially provide a new platform for the development of multi-modal imaging probes. PMID:26147906

Separation of Gd-humic complexes and Gd-based magnetic resonance imaging contrast agent in river water with QAE-Sephadex A-25 for the fractionation analysis.

PubMed

Matsumiya, Hiroaki; Inoue, Hiroto; Hiraide, Masataka

2014-10-01

Gadolinium complexed with naturally occurring, negatively charged humic substances (humic and fulvic acids) was collected from 500 mL of sample solution onto a column packed with 150 mg of a strongly basic anion-exchanger (QAE-Sephadex A-25). A Gd-based magnetic resonance imaging contrast agent (diethylenetriamine-N,N,N',N″,N″-pentaacetato aquo gadolinium(III), Gd-DTPA(2-)) was simultaneously collected on the same column. The Gd-DTPA complex was desorbed by anion-exchange with 50mM tetramethylammonium sulfate, leaving the Gd-humic complexes on the column. The Gd-humic complexes were subsequently dissociated with 1M nitric acid to desorb the humic fraction of Gd. The two-step desorption with small volumes of the eluting agents allowed the 100-fold preconcentration for the fractionation analysis of Gd at low ng L(-1) levels by inductively coupled plasma-mass spectrometry (ICP-MS). On the other hand, Gd(III) neither complexed with humic substances nor DTPA, i.e., free species, was not sorbed on the column. The free Gd in the effluent was preconcentrated 100-fold by a conventional solid-phase extraction with an iminodiacetic acid-type chelating resin and determined by ICP-MS. The proposed analytical fractionation method was applied to river water samples. Copyright © 2014 Elsevier B.V. All rights reserved.

A highly stable gadolinium complex with a fast, associative mechanism of water exchange.

PubMed

Thompson, Marlon K; Botta, Mauro; Nicolle, Gaëlle; Helm, Lothar; Aime, Silvio; Merbach, André E; Raymond, Kenneth N

2003-11-26

The stability and water exchange dynamics of gadolinium (GdIII) complexes are critical characteristics that determine their effectiveness as contrast agents for magnetic resonance imaging (MRI). A new heteropodal GdIII chelate, [Gd-TREN-bis(6-Me-HOPO)-(TAM-TRI)(H2O)2] (Gd-2), is presented which is based on a hydroxypyridinate (HOPO)-terephthalamide (TAM) ligand design. Thermodynamic equilibrium constants for the acid-base properties and the GdIII complexation strength of TREN-bis(6-Me-HOPO)-(TAM-TRI) (2) were measured by potentiometric and spectrophotometric titration techniques, respectively. The pGd of 2 is 20.6 (pH 7.4, 25 degrees C, I = 0.1 M), indicating that Gd-2 is of more than sufficient thermodynamic stability for in vivo MRI applications. The water exchange rate of Gd-2 (kex = 5.3(+/-0.6) x 107 s-1) was determined by variable temperature 17O NMR and is in the fast exchange regime - ideal for MRI. Variable pressure 17O NMR was used to determine the volume of activation (DeltaV) of Gd-2. DeltaV for Gd-2 is -5 cm3 mol-1, indicative of an interchange associative (Ia) water exchange mechanism. The results reported herein are important as they provide insight into the factors influencing high stability and fast water exchange in the HOPO series of complexes, potentially future clinical contrast agents.

Lanthanide Oleates: Chelation, Self-assembly, and Exemplification of Ordered Nanostructured Colloidal Contrast Agents for Medical Imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Guozhen; Conn, Charlotte E.; Drummond, Calum J.

2010-01-12

Eight lanthanide(III) oleates have been prepared and characterized. The chelation and self-assembly structures of these rare-earth oleates have been studied by elemental analysis, Fourier transfer infrared spectroscopy (FTIR), and X-ray powder diffraction (XRD) analysis. Elemental analysis and FTIR results indicate that three oleate anions are complexed with one lanthanide cation and, with the exception of anhydrous cerium(III) oleate, form either a mono- or a hemihydrate. The X-ray analysis showed that the neat lanthanide soaps have a lamellar bilayer structure at room temperature. The thermal behavior has been investigated by cross-polarized optical microscopy (POM), differential scanning calorimetry (DSC), and thermogravimetric analysismore » (TGA). POM scans showed that all the lanthanide oleates form a lamellar phase in the presence of excess water. Small-angle X-ray scattering (SAXS) and XRD were used to investigate the internal structure of the bulk lanthanide oleates in excess water, and these X-ray results confirmed that the lanthanide oleates do not swell in water. Select lanthanide oleates were dispersed in water to form nonswelling lamellar submicrometer particles, confirmed by dynamic light scattering (DLS) and synchrotron SAXS measurements. NMR results indicated that colloidal dispersions of lanthanide oleates containing paramagnetic ions, such as gadolinium(III), terbium(III), and dysprosium(III), have a significant effect on the longitudinal (T{sub 1}) and transverse (T{sub 2}) relaxation times of protons in water. Time-resolved fluorescence measurements have demonstrated that colloidal dispersions of europium(III) oleate exhibit strong luminescence. The rare earth metal soaps exemplify the potential of self-assembled chelating amphiphiles as contrast agents in medical imaging modalities such as magnetic resonance imaging (MRI) and fluorescence imaging.« less

Cloud point extraction: an alternative to traditional liquid-liquid extraction for lanthanides(III) separation.

PubMed

Favre-Réguillon, Alain; Draye, Micheline; Lebuzit, Gérard; Thomas, Sylvie; Foos, Jacques; Cote, Gérard; Guy, Alain

2004-06-17

Cloud point extraction (CPE) was used to extract and separate lanthanum(III) and gadolinium(III) nitrate from an aqueous solution. The methodology used is based on the formation of lanthanide(III)-8-hydroxyquinoline (8-HQ) complexes soluble in a micellar phase of non-ionic surfactant. The lanthanide(III) complexes are then extracted into the surfactant-rich phase at a temperature above the cloud point temperature (CPT). The structure of the non-ionic surfactant, and the chelating agent-metal molar ratio are identified as factors determining the extraction efficiency and selectivity. In an aqueous solution containing equimolar concentrations of La(III) and Gd(III), extraction efficiency for Gd(III) can reach 96% with a Gd(III)/La(III) selectivity higher than 30 using Triton X-114. Under those conditions, a Gd(III) decontamination factor of 50 is obtained.

Gadolinium Deposition in Human Brain Tissues after Contrast-enhanced MR Imaging in Adult Patients without Intracranial Abnormalities.

PubMed

McDonald, Robert J; McDonald, Jennifer S; Kallmes, David F; Jentoft, Mark E; Paolini, Michael A; Murray, David L; Williamson, Eric E; Eckel, Laurence J

2017-11-01

Purpose To determine whether gadolinium deposits in neural tissues of patients with intracranial abnormalities following intravenous gadolinium-based contrast agent (GBCA) exposure might be related to blood-brain barrier integrity by studying adult patients with normal brain pathologic characteristics. Materials and Methods After obtaining antemortem consent and institutional review board approval, the authors compared postmortem neuronal tissue samples from five patients who had undergone four to 18 gadolinium-enhanced magnetic resonance (MR) examinations between 2005 and 2014 (contrast group) with samples from 10 gadolinium-naive patients who had undergone at least one MR examination during their lifetime (control group). All patients in the contrast group had received gadodiamide. Neuronal tissues from the dentate nuclei, pons, globus pallidus, and thalamus were harvested and analyzed with inductively coupled plasma mass spectrometry (ICP-MS), transmission electron microscopy with energy-dispersive x-ray spectroscopy, and light microscopy to quantify, localize, and assess the effects of gadolinium deposition. Results Tissues from the four neuroanatomic regions of gadodiamide-exposed patients contained 0.1-19.4 μg of gadolinium per gram of tissue in a statistically significant dose-dependent relationship (globus pallidus: ρ = 0.90, P = .04). In contradistinction, patients in the control group had undetectable levels of gadolinium with ICP-MS. All patients had normal brain pathologic characteristics at autopsy. Three patients in the contrast group had borderline renal function (estimated glomerular filtration rate <45 mL/min/1.73 m 2 ) and hepatobiliary dysfunction at MR examination. Gadolinium deposition in the contrast group was localized to the capillary endothelium and neuronal interstitium and, in two cases, within the nucleus of the cell. Conclusion Gadolinium deposition in neural tissues after GBCA administration occurs in the absence of intracranial abnormalities that might affect the permeability of the blood-brain barrier. These findings challenge current understanding of the biodistribution of these contrast agents and their safety. © RSNA, 2017.

Chelation therapy to treat atherosclerosis, particularly in diabetes: is it time to reconsider?

PubMed

Lamas, Gervasio A; Ergui, Ian

2016-08-01

Case reports and case series have suggested a possible beneficial effect of chelation therapy in patients with atherosclerotic disease. Small randomized trials conducted in patients with angina or peripheral artery disease, however, were not sufficiently powered to provide conclusive evidence on clinical outcomes. The Trial to Assess Chelation Therapy (TACT) was the first randomized trial adequately powered to detect the effects of chelation therapy on clinical endpoints. We discuss results and future research. Expert commentary: Chelation reduced adverse cardiovascular events in a post myocardial infarction (MI) population. Patients with diabetes demonstrated even greater benefit, with a number needed to treat of 6.5 patients to prevent a cardiac event over 5 years, with a 41% relative reduction in risk of a cardiac event (p = 0.0002). These results led to the revision of the ACC/AHA guideline recommendations for chelation therapy, changing its classification from class III to class IIb. TACT2, a replicative trial, will assess the effects of chelation therapy on cardiovascular outcomes in diabetic patients with a prior myocardial infarction. We are seeking participating sites for TACT2.

Gd-DTPA L-cystine bisamide copolymers as novel biodegradable macromolecular contrast agents for MR blood pool imaging.

PubMed

Kaneshiro, Todd L; Ke, Tianyi; Jeong, Eun-Kee; Parker, Dennis L; Lu, Zheng-Rong

2006-06-01

The purpose of this study was to synthesize biodegradable Gd-DTPA L-cystine bisamide copolymers (GCAC) as safe and effective, macromolecular contrast agents for magnetic resonance imaging (MRI) and to evaluate their biodegradability and efficacy in MR blood pool imaging in an animal model. Three new biodegradable GCAC with different substituents at the cystine bisamide [R = H (GCAC), CH2CH2CH3 (Gd-DTPA L-cystine bispropyl amide copolymers, GCPC), and CH(CH3)2 (Gd-DTPA cystine bisisopropyl copolymers, GCIC)] were prepared by the condensation copolymerization of diethylenetriamine pentaacetic acid (DTPA) dianhydride with cystine bisamide or bisalkyl amides, followed by complexation with gadolinium triacetate. The degradability of the agents was studied in vitro by incubation in 15 microM cysteine and in vivo with Sprague-Dawley rats. The kinetics of in vivo contrast enhancement was investigated in Sprague-Dawley rats on a Siemens Trio 3 T scanner. The apparent molecular weight of the polydisulfide Gd(III) chelates ranged from 22 to 25 kDa. The longitudinal (T1) relaxivities of GCAC, GCPC, and GCIC were 4.37, 5.28, and 5.56 mM(-1) s(-1) at 3 T, respectively. The polymeric ligands and polymeric Gd(III) chelates readily degraded into smaller molecules in incubation with 15 microM cysteine via disulfide-thiol exchange reactions. The in vitro degradation rates of both the polymeric ligands and macromolecular Gd(III) chelates decreased as the steric effect around the disulfide bonds increased. The agents readily degraded in vivo, and the catabolic degradation products were detected in rat urine samples collected after intravenous injection. The agents showed strong contrast enhancement in the blood pool, major organs, and tissues at a dose of 0.1 mmol Gd/kg. The difference of their in vitro degradability did not significantly alter the kinetics of in vivo contrast enhancement of the agents. These novel GCAC are promising contrast agents for cardiovascular and tumor MRI, which are later cleaved into low molecular weight Gd(III) chelates and rapidly cleared from the body.

Self-assembly of PEGylated tetra-phenylalanine derivatives: structural insights from solution and solid state studies

PubMed Central

Diaferia, Carlo; Mercurio, Flavia Anna; Giannini, Cinzia; Sibillano, Teresa; Morelli, Giancarlo; Leone, Marilisa; Accardo, Antonella

2016-01-01

Water soluble fibers of PEGylated tetra-phenylalanine (F4), chemically modified at the N-terminus with the DOTA chelating agent, have been proposed as innovative contrast agent (CA) in Magnetic Resonance Imaging (MRI) upon complexation of the gadolinium ion. An in-depth structural characterization of PEGylated F4-fibers, in presence (DOTA-L6-F4) and in absence of DOTA (L6-F4), is reported in solution and at the solid state, by a multiplicity of techniques including CD, FTIR, NMR, DLS, WAXS and SAXS. This study aims to better understand how the aggregation process influences the performance of nanostructures as MRI CAs. Critical aggregation concentrations for L6-F4 (43 μM) and DOTA-L6-F4 (75 μM) indicate that self-aggregation process occurs in the same concentration range, independently of the presence of the CA. The driving force for the aggregation is the π-stacking between the side chains of the aromatic framework. CD, FTIR and WAXS measurements indicate an antiparallel β-sheet organization of the monomers in the resulting fibers. Moreover, WAXS and FTIR experiments point out that in solution the nanomaterials retain the same morphology and monomer organizations of the solid state, although the addition of the DOTA chelating agent affects the size and the degree of order of the fibers. PMID:27220817

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pierson, Stephen A.; Nacham, Omprakash; Clark, Kevin D.

Magnetic ionic liquids (MILs) are distinguished from traditional ionic liquids (ILs) by the incorporation of a paramagnetic component within their chemical structure. Hydrophobic MILs are novel solvents that can be used in many applications, including liquid–liquid extraction (LLE) and catalysis. Low viscosity and low water solubility are essential features that determine their feasibility in LLE. Here, we synthesized extremely hydrophobic MILs by using transition and rare earth metal hexafluoroacetylacetonate chelated anions paired with the trihexyl(tetradecyl)phosphonium ([P 66614 +]) cation. Hydrophobic MILs exhibiting water solubilities less than 0.01% (v/v) were synthesized in a rapid two-step procedure. Furthermore, the viscosities of themore » MILs are among some of the lowest ever reported for hydrophobic MILs (276.5–927.9 centipoise (cP) at 23.7 °C) dramatically improving the ease of handling these liquids. For the first time, the magnetic properties of MILs possessing hexafluoroacetylacetonate chelated metal anions synthesized in this study are reported using a superconducting quantum interference device (SQUID) magnetometer. We also achieved an effective magnetic moments (μ eff) as high as 9.7 and 7.7 Bohr magnetons (μ B) by incorporating high spin dysprosium and gadolinium ions, respectively, into the anion component of the MIL. The low viscosity, high hydrophobicity, and large magnetic susceptibility of these MILs make them highly attractive and promising solvents for separations and purification, liquid electrochromic materials, catalytic studies, as well as microfluidic applications.« less

Preparation of PEG-conjugated fullerene containing Gd3+ ions for photodynamic therapy.

PubMed

Liu, Jian; Ohta, Shin-Ichi; Sonoda, Akinaga; Yamada, Masatoshi; Yamamoto, Masaya; Nitta, Norihisa; Murata, Kiyoshi; Tabata, Yasuhiko

2007-01-22

A novel photosensitizer with magnetic resonance imaging (MRI) activity was designed from fullerene (C(60)) for efficient photodynamic therapy (PDT) of tumor. After chemical conjugation of polyethylene glycol (PEG) to C(60) (C(60)-PEG), diethylenetriaminepentaacetic acid (DTPA) was subsequently introduced to the terminal group of PEG to prepare PEG-conjugated C(60) (C(60)-PEG-DTPA). The C(60)-PEG-DTPA was mixed with gadolinium acetate solution to obtain Gd(3+)-chelated C(60)-PEG (C(60)-PEG-Gd). Following intravenous injection of C(60)-PEG-Gd into tumor-bearing mice, the PDT anti-tumor effect and the MRI tumor imaging were evaluated. The similar O(2)(*-)generation was observed with or without Gd(3+) chelation upon light irradiation. Both of the C(60)-PEG-Gd and Magnevist(R) aqueous solutions exhibited a similar MRI activity. When intravenously injected into tumor-bearing mice, the C(60)-PEG-Gd maintained an enhanced MRI signal at the tumor tissue for a longer time period than Magnevist(R). Injection of C(60)-PEG-Gd plus light irradiation showed significant tumor PDT effect although the effect depended on the timing of light irradiation. The PDT efficacy of C(60)-PEG-Gd was observed at the time when the tumor accumulation was detected by the enhanced intensity of MRI signal. This therapeutic and diagnostic hybrid system is a promising tool to enhance the PDT efficacy for tumor.

Improved Peritoneal Cavity and Abdominal Organ Imaging Using a Biphasic Contrast Agent Protocol and Spectral Photon Counting Computed Tomography K-Edge Imaging.

PubMed

Si-Mohamed, Salim; Thivolet, Arnaud; Bonnot, Pierre-Emmanuel; Bar-Ness, Daniel; Képénékian, Vahan; Cormode, David P; Douek, Philippe; Rousset, Pascal

2018-05-23

To validate in vitro the capability of a high-spatial-resolution prototype spectral photon-counting computed tomography (SPCCT) scanner to differentiate between 2 contrast agents and to assess in vivo the image quality and the feasibility to image the peritoneal cavity in rats using the 2 contrast agents simultaneously within the vascular and peritoneal compartments. The authors performed SPCCT imaging (100 mAs, 120 kVp) with energy bin thresholds set to 30, 51, 64, 72, and 85 keV in vitro on a custom-made polyoxymethylene cylindrical phantom consisting of tubes with dilutions of both contrast agents and in vivo on 2 groups of adult rats using 2 injection protocols. Approval from the institutional animal ethics committee was obtained. One group received macrocylic gadolinium chelate intraperitoneal (IP) and iodine intravenous (IV) injections (protocol A, n = 3), whereas the second group received iodine IP and gadolinium IV (protocol B, n = 3). Helical scans were performed 35 minutes after IP injection and 20 seconds after IV injection. The SPCCT and contrast material images, that is, iodine and gadolinium maps, were reconstructed with a field of view of 160 mm, an isotropic voxel size of 250 μm, and a matrix size of 640 × 640 pixels using a soft reconstruction kernel. The SPCCT images were reconstructed with 2 different spatial resolutions to compare the image quality (sharpness, diagnostic quality, and organ visualization) of SPCCT (250 μm) with single-energy computed tomography (CT) (600 μm). Two radiologists evaluated the peritoneal opacification index in 13 regions (score = 0-3 per region) on each type of image. Concentrations of contrast agents were measured in the organs of interest. In vitro, the concentration measurements correlated well with the expected concentrations. The linear regressions both had R values of 0.99, slopes of 0.84 and 0.87, and offsets at -0.52 and -0.38 mg/mL for iodine and gadolinium, respectively. In vivo, the SPCCT images were of better diagnostic quality, with increased sharpness compared with the CT-like images (P < 0.0001). Intraperitoneal diffusion was excellent, with similar peritoneal opacification index on SPCCT images and overlay of contrast material maps (P = 1) without a significant difference between protocol A (37.0 ± 1.7) and protocol B (35.3 ± 1.5) (P = 0.34). Only the contrast material maps demonstrated clear visual separation of the contrast agents, allowing specific quantification of the physiological enhancement in the liver, spleen, and kidney and the urinary clearance in the renal pelvis and bladder. Renal excretion of the contrast agents injected IP was observed and was consistent with blood diffusion. Spectral photon-counting CT can be used to perform a complete peritoneal dual-contrast protocol, enabling a good assessment of the peritoneal cavity and abdominal organs in rats.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

Hepatocellular carcinoma metastasizing to the skull base involving multiple cranial nerves.

PubMed

Kim, Soo Ryang; Kanda, Fumio; Kobessho, Hiroshi; Sugimoto, Koji; Matsuoka, Toshiyuki; Kudo, Masatoshi; Hayashi, Yoshitake

2006-11-07

We describe a rare case of HCV-related recurrent multiple hepatocellular carcinoma (HCC) metastasizing to the skull base involving multiple cranial nerves in a 50-year-old woman. The patient presented with symptoms of ptosis, fixation of the right eyeball, and left abducens palsy, indicating disturbances of the right oculomotor and trochlear nerves and bilateral abducens nerves. Brain contrast-enhanced computed tomography (CT) revealed an ill-defined mass with abnormal enhancement around the sella turcica. Brain magnetic resonance imaging (MRI) disclosed that the mass involved the clivus, cavernous sinus, and petrous apex. On contrast-enhanced MRI with gadolinium-chelated contrast medium, the mass showed inhomogeneous intermediate enhancement. The diagnosis of metastatic HCC to the skull base was made on the basis of neurological findings and imaging studies including CT and MRI, without histological examinations. Further studies may provide insights into various methods for diagnosing HCC metastasizing to the craniospinal area.

Applications of optically detected MRI for enhanced contrast and penetration in metal

NASA Astrophysics Data System (ADS)

Ruangchaithaweesuk, Songtham; Yu, Dindi S.; Garcia, Nissa C.; Yao, Li; Xu, Shoujun

2012-10-01

We report quantitative measurements using optically detected magnetic resonance imaging (MRI) for enhanced pH contrast and flow inside porous metals. Using a gadolinium chelate as the pH contrast agent, we show the response is 0.6 s-1 mM-1 per pH unit at the ambient magnetic field for the pH range 6-8.5. A stopped flow scheme was used to directly measure T1 relaxation time to determine the relaxivity. Flow profiles and images were obtained for a series of porous metals with different average pore sizes. The signal amplitudes and spatial distributions were compared. A clogged region in one of the samples was revealed using optically detected MRI but not optical imaging or scanning electron microscopy. These applications will significantly broaden the impact of optically detected MRI in chemical imaging and materials research.

A novel paramagnetic substrate for detecting myeloperoxidase activity in vivo.

PubMed

Shazeeb, Mohammed S; Xie, Yang; Gupta, Suresh; Bogdanov, Alexei A

2012-01-01

Bis-phenylamides and bis-hydroxyindolamides of diethylenetriaminepentaacetic acid-gadolinium (DTPA(Gd)) are paramagnetic reducing substrates of peroxidases that enable molecular imaging of peroxidase activity in vivo. Specifically, gadolinium chelates of bis-5-hydroxytryptamide-DTPA (bis-5HT-DTPA(Gd)) have been used to image localized inflammation in animal models by detecting neutrophil-derived myeloperoxidase (MPO) activity at the inflammation site. However, in other preclinical disease models, bis-5HT-DTPA(Gd) presents technical challenges due to its limited solubility in vivo. Here we report a novel MPO-sensing probe obtained by replacing the reducing substrate serotonin (5-HT) with 5-hydroxytryptophan (HTrp). Characterization of the resulting probe (bis-HTrp-DTPA(Gd)) in vitro using nuclear magnetic resonance spectroscopy and enzyme kinetic analysis showed that bis-HTrp-DTPA(Gd) (1) improves solubility in water; (2) acts as a substrate for both horseradish peroxidase and MPO enzymes; (3) induces cross-linking of proteins in the presence of MPO; (4) produces oxidation products, which bind to plasma proteins; and (5) unlike bis-5HT-DTPA(Gd), does not follow first-order reaction kinetics. In vivo magnetic resonance imaging (MRI) in mice demonstrated that bis-HTrp-DTPA(Gd) was retained for up to 5 days in MPO-containing sites and cleared faster than bis-5HT-DTPA(Gd) from MPO-negative sites. Bis-HTrp-DTPA(Gd) should offer improvements for MRI of MPO-mediated inflammation in vivo, especially in high-field MRI, which requires a higher dose of contrast agent.

Superparamagnetic And Paramagnetic MRI Contrast Agents: Application Of Rapid Magnetic Resonance Imaging To Assess Renal Function

NASA Astrophysics Data System (ADS)

Carvlin, Mark J.; Renshaw, Perry F.; Arger, Peter; Kundel, Harold L.; Dougherty, Larry; Axel, Leon; Kassab, Eleanor; Moore, Bethanne

1988-06-01

The paramagnetic chelate complex, gadolinium-diethylene-triamine-pentaacetic acid, Gd-DTPA, and superparamagnetic particles, such as those composed of dextran coated magnetite, function as magnetic resonance contrast agents by changing the relaxation rates, 1/T1 and 1/T2. The effects that these agents have upon MR signal intensity are determined by: the inherent biophysical properties of the tissue being imaged, the concentration of the contrast agent and the data acquisition scheme (pulse sequence parameters) employed. Following the time course of MR signal change in the first minutes after the injection of contrast agent(s) allows a dynamic assessment of organ functions in a manner analogous to certain nuclear medicine studies. In order to study renal function, sequential MR fast scan images, gradient echo (TR=35/TE=7 msec, flip angle=25 degrees), were acquired, one every 12 seconds, after intravenous injection of Gd-DTPA and/or dextran-magnetite. Gd-DTPA, which is freely filtered at the glomerulus and is neither secreted nor reabsorbed, provides information concerning renal perfusion, glomerular filtration and tubular concentrating ability. Dextran-magnetite (200 A diameter), which is primarily contained within the intravascular space shortly after injection, provides information on blood flow to and distribution within the kidney. The MR signal change observed after administration of contrast agents varied dramatically depending upon the agents injected and the imaging parameters used. Hence a broad range of physiolgic processes may be described using these techniques, i.e. contrast agent enhanced functional MR examinations.

A polymeric micelle magnetic resonance imaging (MRI) contrast agent reveals blood-brain barrier (BBB) permeability for macromolecules in cerebral ischemia-reperfusion injury.

PubMed

Shiraishi, Kouichi; Wang, Zuojun; Kokuryo, Daisuke; Aoki, Ichio; Yokoyama, Masayuki

2017-05-10

Blood-brain barrier (BBB) opening is a key phenomenon for understanding ischemia-reperfusion injuries that are directly linked to hemorrhagic transformation. The recombinant human tissue-type plasminogen activator (rtPA) increases the risk of symptomatic intracranial hemorrhages. Recent imaging technologies have advanced our understanding of pathological BBB disorders; however, an ongoing challenge in the pre-"rtPA treatment" stage is the task of developing a rigorous method for hemorrhage-risk assessments. Therefore, we examined a novel method for assessment of rtPA-extravasation through a hyper-permeable BBB. To examine the image diagnosis of rtPA-extravasation for a rat transient occlusion-reperfusion model, in this study we used a polymeric micelle MRI contrast-agent (Gd-micelles). Specifically, we used two MRI contrast agents at 1h after reperfusion. Gd-micelles provided very clear contrast images in 15.5±10.3% of the ischemic hemisphere at 30min after i.v. injection, whereas a classic gadolinium chelate MRI contrast agent provided no satisfactorily clear images. The obtained images indicate both the hyper-permeable BBB area for macromolecules and the distribution area of macromolecules in the ischemic hemisphere. Owing to their large molecular weight, Gd-micelles remained in the ischemic hemisphere through the hyper-permeable BBB. Our results indicate the feasibility of a novel clinical diagnosis for evaluating rtPA-related hemorrhage risks. Copyright © 2017 Elsevier B.V. All rights reserved.

Oral chelators deferasirox and deferiprone for transfusional iron overload in thalassemia major: new data, new questions

PubMed Central

Neufeld, Ellis J.

2006-01-01

For nearly 30 years, patients with transfusional iron overload have depended on nightly deferoxamine infusions for iron chelation. Despite dramatic gains in life expectancy in the deferoxamine era for patients with transfusion-dependent anemias, the leading cause of death for young adults with thalassemia major and related disorders has been cardiac disease from myocardial iron deposition. Strategies to reduce cardiac disease by improving chelation regimens have been of the highest priority. These strategies have included development of novel oral iron chelators to improve compliance, improved assessment of cardiac iron status, and careful epidemiologic assessment of European outcomes with deferiprone, an oral alternative chelator available for about a decade. Each of these strategies is now bearing fruit. The novel oral chelator deferasirox was recently approved by the Food and Drug Administration (FDA); a randomized clinical trial demonstrates that deferasirox at 20 to 30 mg/kg/d can maintain or improve hepatic iron in thalassemia as well as deferoxamine. A randomized trial based on cardiac T2* magnetic resonance imaging (MRI) suggests that deferiprone can unload myocardial iron faster than deferoxamine. Retrospective epidemiologic data suggest dramatic reductions in cardiac events and mortality in Italian subjects exposed to deferiprone compared with deferoxamine. These developments herald a new era for iron chelation, but many unanswered questions remain. PMID:16627763

Sensitive and transportable gadolinium-core plastic scintillator sphere for neutron detection and counting

NASA Astrophysics Data System (ADS)

Dumazert, Jonathan; Coulon, Romain; Carrel, Frédérick; Corre, Gwenolé; Normand, Stéphane; Méchin, Laurence; Hamel, Matthieu

2016-08-01

Neutron detection forms a critical branch of nuclear-related issues, currently driven by the search for competitive alternative technologies to neutron counters based on the helium-3 isotope. The deployment of plastic scintillators shows a high potential for efficient detectors, safer and more reliable than liquids, more easily scalable and cost-effective than inorganic. In the meantime, natural gadolinium, through its 155 and mostly 157 isotopes, presents an exceptionally high interaction probability with thermal neutrons. This paper introduces a dual system including a metal gadolinium core inserted at the center of a high-scale plastic scintillator sphere. Incident fast neutrons are thermalized by the scintillator shell and then may be captured with a significant probability by gadolinium 155 and 157 nuclei in the core. The deposition of a sufficient fraction of the capture high-energy prompt gamma signature inside the scintillator shell will then allow discrimination from background radiations by energy threshold, and therefore neutron detection. The scaling of the system with the Monte Carlo MCNPX2.7 code was carried out according to a tradeoff between the moderation of incident fast neutrons and the probability of slow neutron capture by a moderate-cost metal gadolinium core. Based on the parameters extracted from simulation, a first laboratory prototype for the assessment of the detection method principle has been synthetized. The robustness and sensitivity of the neutron detection principle are then assessed by counting measurement experiments. Experimental results confirm the potential for a stable, highly sensitive, transportable and cost-efficient neutron detector and orientate future investigation toward promising axes.

The influence of functional groups on the permeation and distribution of antimycobacterial rhodamine chelators.

PubMed

Moniz, T; Leite, A; Silva, T; Gameiro, P; Gomes, M S; de Castro, B; Rangel, M

2017-10-01

We formerly hypothesized a mechanism whereby the antimycobacterial efficiency of a set of rhodamine labelled iron chelators is improved via the rhodamine fluorophore which enhances the chelators' permeation properties through membranes. To validate our hypothesis in a cellular context and to understand the influence of the structure of the fluorophore on the chelator's uptake and distribution within macrophages we now report comparative confocal microscopy studies performed with a set of rhodamine labelled chelators. We identify the functional groups of the chelator's framework that favor uptake by macrophages and conclude that the antimycobacterial effect is strongly related with the capacity of the chelator to distribute within the host cell and its compartments, a property that is closely related with the chelators' ability to interact with membranes. The quantification of the chelators' interaction with membranes was assessed through measurement of the corresponding partition constants in liposomes. The overall results support that the compounds which are preferentially taken up are the most efficient antimycobacterial chelators and for that reason we infer that the biological activity is modulated by the structural features of the fluorophore. Copyright © 2017 Elsevier Inc. All rights reserved.

Dual-contrast agent photon-counting computed tomography of the heart: initial experience.

PubMed

Symons, Rolf; Cork, Tyler E; Lakshmanan, Manu N; Evers, Robert; Davies-Venn, Cynthia; Rice, Kelly A; Thomas, Marvin L; Liu, Chia-Ying; Kappler, Steffen; Ulzheimer, Stefan; Sandfort, Veit; Bluemke, David A; Pourmorteza, Amir

2017-08-01

To determine the feasibility of dual-contrast agent imaging of the heart using photon-counting detector (PCD) computed tomography (CT) to simultaneously assess both first-pass and late enhancement of the myocardium. An occlusion-reperfusion canine model of myocardial infarction was used. Gadolinium-based contrast was injected 10 min prior to PCD CT. Iodinated contrast was infused immediately prior to PCD CT, thus capturing late gadolinium enhancement as well as first-pass iodine enhancement. Gadolinium and iodine maps were calculated using a linear material decomposition technique and compared to single-energy (conventional) images. PCD images were compared to in vivo and ex vivo magnetic resonance imaging (MRI) and histology. For infarct versus remote myocardium, contrast-to-noise ratio (CNR) was maximal on late enhancement gadolinium maps (CNR 9.0 ± 0.8, 6.6 ± 0.7, and 0.4 ± 0.4, p < 0.001 for gadolinium maps, single-energy images, and iodine maps, respectively). For infarct versus blood pool, CNR was maximum for iodine maps (CNR 11.8 ± 1.3, 3.8 ± 1.0, and 1.3 ± 0.4, p < 0.001 for iodine maps, gadolinium maps, and single-energy images, respectively). Combined first-pass iodine and late gadolinium maps allowed quantitative separation of blood pool, scar, and remote myocardium. MRI and histology analysis confirmed accurate PCD CT delineation of scar. Simultaneous multi-contrast agent cardiac imaging is feasible with photon-counting detector CT. These initial proof-of-concept results may provide incentives to develop new k-edge contrast agents, to investigate possible interactions between multiple simultaneously administered contrast agents, and to ultimately bring them to clinical practice.

Enhanced conjugation stability and blood circulation time of macromolecular gadolinium-DTPA contrast agent.

PubMed

Jenjob, Ratchapol; Kun, Na; Ghee, Jung Yeon; Shen, Zheyu; Wu, Xiaoxia; Cho, Steve K; Lee, Don Haeng; Yang, Su-Geun

2016-04-01

In this study, we prepared macromolecular MR T1 contrast agent: pullulan-conjugated Gd diethylene triamine pentaacetate (Gd-DTPA-Pullulan) and estimated residual free Gd(3+), chelation stability in competition with metal ions, plasma and tissue pharmacokinetics, and abdominal MR contrast on rats. Residual free Gd(3+) in Gd-DTPA-Pullulan was measured using colorimetric spectroscopy. The transmetalation of Gd(3+) incubated with Ca(2+) was performed by using a dialysis membrane (MWCO 100-500 Da) and investigated by ICP-OES. The plasma concentration profiles of Gd-DTPA-Pullulan were estimated after intravenous injection at a dose 0.1 mmol/kg of Gd. The coronal-plane abdominal images of normal rats were observed by MR imaging. The content of free Gd(3+), the toxic residual form, was less than 0.01%. Chelation stability of Gd-DTPA-Pullulan was estimated, and only 0.2% and 0.00045% of Gd(3+) were released from Gd-DTPA-Pullulan after 2h incubation with Ca(2+) and Fe(2+), respectively. Gd-DTPA-Pullulan displayed the extended plasma half-life (t1/2,α=0.43 h, t1/2,β=2.32 h), much longer than 0.11h and 0.79 h of Gd-EOB-DTPA. Abdominal MR imaging showed Gd-DTPA-Pullulan maintained initial MR contrast for 30 min. The extended plasma half-life of Gd-DTPA-Pullulan probably allows the prolonged MR acquisition time in clinic with enhanced MR contrast. Copyright © 2016 Elsevier B.V. All rights reserved.

Impact of educational programme regarding chelation therapy on the quality of life for B-thalassemia major children.

PubMed

Abu Samra, Omayma; Auda, Wafaa; Kamhawy, Heba; Al-Tonbary, Youssef

2015-06-01

Objectives Thalassemia is the most common genetic disorder in Egypt, with an estimated carrier rate of 9-10%. It is a genetic blood disorder which can be fatal if proper chelation is not received. The introduction of chelating agents capable of removing excessive iron from the body has dramatically increased life expectancy and improved the overall quality of life. The aim of this study was to assess the impact of educational programmes regarding chelation therapy on the quality of life of thalassemic children. Methods The study was carried out at the Mansoura University Children's Hospital in the period between March 2010 and May 2011. It included 173 B-thalassemia children (84 boys and 89 girls) with age ranging between 8-18 years. The researcher used a predesigned interviewing questionnaire to collect data regarding children's knowledge about thalassemia and its management, especially regarding chelation therapy. The paediatric quality-of-life inventory tool (Peds QL 4.0 generic core) was also used to assess the studied children's quality of life. Results There was a significant statistical difference of the studied children's knowledge regarding chelation therapy and their quality of life. Conclusion There was a positive effect of the educational programme in improving children's knowledge score and their quality of life. Application of educational programmes for thalassemic children and their nurses regarding chelation therapy and its importance in preventing thalassemia complications is established.

Biomedical Nanocrystal Agents: Design, Synthesis, and Applications

NASA Astrophysics Data System (ADS)

Cho, Minjung

In these days, nanomaterials are applied in a variety of biomedical applications including magnetic resonance imaging (MRI), cell imaging, drug delivery, and cell separation. Most MRI contrast agents affect the longitudinal relaxation time (T1) and transverse relaxation time (T2 ) of water protons in the tissue and result in increased positive or negative contrast. Here, we report the optimization of r1 (1/T 1) or r2 (1/T2) relaxivity dynamics with diameter controlled gadolinium oxide nanocrystals (2˜22 nm) and iron based magnetic nanocrystals (4 ˜33 nm). The r1 and r2 MR relaxivity values of hydrated nanocrystals were optimized and examined depending on their core diameter, surface coating, and compositions; the high r1 value of gadolinium oxide was 40-60 S-1mM-1, which is 10-15 fold higher than that of commercial Gd (III) chelates (4.3˜4.6 S-1mM-1). Moreover, in vitro toxicological studies revealed that polymer coated nanocrystals suspensions had no significant effect on human dermal fibroblast (HDF) cells even at high concentration. Towards multimodal imaging or multifunctional ability, we developed the iron oxide/QDs complexes, which consist of cores of iron oxide that act as nucleation sites for fluorescent QDs. The choice of variable QDs helped to visualize and remove large iron oxide materials in a magnetic separation. Additionally, diluted materials concentrated on the magnet could be fluorescently detected even at very low concentration. The designed MRI or multifunctional nanomaterials will give great and powerful uses in biomedical applications.

Crystallography, Spectroscopic Analysis, and Lasing Properties of Nd(3+) :Y3Sc2Al3O12

DTIC Science & Technology

1989-12-01

aluminum garnet (GSAG), are formed from more stable constitu- ent oxides than gallium-containing materials, 2. Experimental Results and such as gadolinium ...the which an assessment can be made regarding aluminum -based systems, such as YAG, YSAG, Nd:YSAG as a laser material. or gadolinium scandium...Structure oxidation state variation or oxygen vacancies, and this problem is greatly reduced in alumi- Yttrium scandium aluminum garnet be- nate systems

The Stoichiometry of Isoquercitrin Complex with Iron or Copper Is Highly Dependent on Experimental Conditions

PubMed Central

Tvrdý, Václav; Karlíčková, Jana; Migkos, Thomas; Mladěnka, Přemysl

2017-01-01

Interaction of flavonoids with transition metals can be partially responsible for their impact on humans. Stoichiometry of the iron/copper complex with a flavonoid glycoside isoquercitrin, a frequent component of food supplements, was assessed using competitive and non-competitive methods in four (patho)physiologically-relevant pH values (4.5. 5.5, 6.8, and 7.5). Isoquercitrin chelated all tested ions (Fe2+, Fe3+, Cu2+, and Cu+) but its affinity for Cu+ ions proved to be very low. In general, the chelation potency dropped with pH lowering. Metal complexes of 1:1 stoichiometry were mostly formed, however, they were not stable and the stoichiometry changed depending on conditions. Isoquercitrin was able to reduce both Cu2+ and Fe3+ ions at low ratios, but its reducing potential was diminished at higher ratios (isoquercitrin to metal) due to the metal chelation. In conclusion, this study emphasizes the need of using multiple different methods for the assessment of chelation potential in moderately-active metal chelators, like flavonoids. PMID:29084179

Gadolinium toxicity and treatment.

PubMed

Ramalho, Joana; Ramalho, Miguel; Jay, Michael; Burke, Lauren M; Semelka, Richard C

2016-12-01

Gadolinium based contrast agents (GBCAs) play an important role in the diagnostic evaluation of many patients. The safety of these agents has been once again questioned after gadolinium deposits were observed and measured in brain and bone of patients with normal renal function. This retention of gadolinium in the human body has been termed "gadolinium storage condition". The long-term and cumulative effects of retained gadolinium in the brain and elsewhere are not as yet understood. Recently, patients who report that they suffer from chronic symptoms secondary to gadolinium exposure and retention created gadolinium-toxicity on-line support groups. Their self-reported symptoms have recently been published. Bone and joint complaints, and skin changes were two of the most common complaints. This condition has been termed "gadolinium deposition disease". In this review we will address gadolinium toxicity disorders, from acute adverse reactions to GBCAs to gadolinium deposition disease, with special emphasis on the latter, as it is the most recently described and least known. Copyright © 2016 Elsevier Inc. All rights reserved.

A choline derivate-modified nanoprobe for glioma diagnosis using MRI

NASA Astrophysics Data System (ADS)

Li, Jianfeng; Huang, Shixian; Shao, Kun; Liu, Yang; An, Sai; Kuang, Yuyang; Guo, Yubo; Ma, Haojun; Wang, Xuxia; Jiang, Chen

2013-04-01

Gadolinium (Gd) chelate contrast-enhanced magnetic resonance imaging (MRI) is a preferred method of glioma detection and preoperative localisation because it offers high spatial resolution and non-invasive deep tissue penetration. Gd-based contrast agents, such as Gd-diethyltriaminepentaacetic acid (DTPA-Gd, Magnevist), are widely used clinically for tumor diagnosis. However, the Gd-based MRI approach is limited for patients with glioma who have an uncompromised blood-brain barrier (BBB). Moreover, the rapid renal clearance and non-specificity of such contrast agents further hinders their prevalence. We present a choline derivate (CD)-modified nanoprobe with BBB permeability, glioma specificity and a long blood half-life. Specific accumulation of the nanoprobe in gliomas and subsequent MRI contrast enhancement are demonstrated in vitro in U87 MG cells and in vivo in a xenograft nude model. BBB and glioma dual targeting by this nanoprobe may facilitate precise detection of gliomas with an uncompromised BBB and may offer better preoperative and intraoperative tumor localization.

Sol-gel synthesis and characterizations of crystalline NaGd(WO4)2 powder for anisotropic transparent ceramic laser application

NASA Astrophysics Data System (ADS)

Durairajan, A.; Thangaraju, D.; Balaji, D.; Moorthy Babu, S.

2013-02-01

NaGd(WO4)2 powders were synthesized at different pH (3.5, 4.5, 5.5, 6.5 and 7.5) values by conventional Pechini method. Sodium and gadolinium nitrate salts and ammonium paratungstate are used as starting precursors. Metal cations were chelated by citric acid and individual citrates were bound together with ethylene glycol. Synthesized gel was analyzed using differential thermal analysis (DTA), thermo gravimetric (TG) and FT-IR spectroscopy to understand the degradation of gel and formation of metal citrates. Calcined powders (250, 600, 700 and 800 °C) were characterized by powder XRD, FT-IR, Raman and FE-SEM analysis. The temperature dependent phase formation was examined by powder XRD. The morphological changes at different pH derived powders were observed with FE-SEM micrographs. Stepwise organic liberation with respect to temperature and presence of carbon content in the pre-fired powder were analyzed using FT-IR analysis. Raman spectrum reveals disordered tungstate vibrations in the NGW matrix.

Towards the Rational Design of MRI Contrast Agents: Electron Spin Relaxation Is Largely Unaffected by the Coordination Geometry of Gadolinium(III)–DOTA-Type Complexes

PubMed Central

Bean, Jonathan F.; Clarkson, Robert B.; Helm, Lothar; Moriggi, Loïck; Sherry, A. Dean

2009-01-01

Electron-spin relaxation is one of the determining factors in the efficacy of MRI contrast agents. Of all the parameters involved in determining relaxivity it remains the least well understood, particularly as it relates to the structure of the complex. One of the reasons for the poor understanding of electron-spin relaxation is that it is closely related to the ligand-field parameters of the Gd3+ ion that forms the basis of MRI contrast agents and these complexes generally exhibit a structural isomerism that inherently complicates the study of electron spin relaxation. We have recently shown that two DOTA-type ligands could be synthesised that, when coordinated to Gd3+, would adopt well defined coordination geometries and are not subject to the problems of intramolecular motion of other complexes. The EPR properties of these two chelates were studied and the results examined with theory to probe their electron-spin relaxation properties. PMID:18283704

In vivo characterization of a smart MRI agent that displays an inverse response to calcium concentration.

PubMed

Mamedov, Ilgar; Canals, Santiago; Henig, Jörg; Beyerlein, Michael; Murayama, Yusuke; Mayer, Hermann A; Logothetis, Nikos K; Angelovski, Goran

2010-12-15

Contrast agents for magnetic resonance imaging (MRI) that exhibit sensitivity toward specific ions or molecules represent a challenging but attractive direction of research. Here a Gd(3+) complex linked to an aminobis(methylenephosphonate) group for chelating Ca(2+) was synthesized and investigated. The longitudinal relaxivity (r(1)) of this complex decreases during the relaxometric titration with Ca(2+) from 5.76 to 3.57 mM(-1) s(-1) upon saturation. The r(1) is modulated by changes in the hydration number, which was confirmed by determination of the luminescence emission lifetimes of the analogous Eu(3+) complex. The initial in vivo characterization of this responsive contrast agent was performed by means of electrophysiology and MRI experiments. The investigated complex is fully biocompatible, having no observable effect on neuronal function after administration into the brain ventricles or parenchyma. Distribution studies demonstrated that the diffusivity of this agent is significantly lower compared with that of gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA).

Gold coated lanthanide phosphate nanoparticles for targeted alpha generator radiotherapy.

PubMed

McLaughlin, Mark F; Woodward, Jonathan; Boll, Rose A; Wall, Jonathan S; Rondinone, Adam J; Kennel, Stephen J; Mirzadeh, Saed; Robertson, J David

2013-01-01

Targeted radiotherapies maximize cytotoxicty to cancer cells. In vivo α-generator targeted radiotherapies can deliver multiple α particles to a receptor site dramatically amplifying the radiation dose delivered to the target. The major challenge with α-generator radiotherapies is that traditional chelating moieties are unable to sequester the radioactive daughters in the bioconjugate which is critical to minimize toxicity to healthy, non-target tissue. The recoil energy of the (225)Ac daughters following α decay will sever any metal-ligand bond used to form the bioconjugate. This work demonstrates that an engineered multilayered nanoparticle-antibody conjugate can deliver multiple α radiations and contain the decay daughters of (225)Ac while targeting biologically relevant receptors in a female BALB/c mouse model. These multi-shell nanoparticles combine the radiation resistance of lanthanide phosphate to contain (225)Ac and its radioactive decay daughters, the magnetic properties of gadolinium phosphate for easy separation, and established gold chemistry for attachment of targeting moieties.

Right ventricular stress-induced perfusion defects and late gadolinium enhancement in coronary artery disease.

PubMed

Milks, Michael Wesley; Upadhya, Bharathi; Hall, Michael E; Vasu, Sujethra; Hundley, William Gregory; Stacey, Richard Brandon

2015-01-01

The assessment of right ventricular (RV) perfusion defects has remained challenging during vasodilator stress perfusion with cardiovascular magnetic resonance (CMR). The significance of RV signal abnormalities during vasodilator stress perfusion and late gadolinium-enhanced CMR is yet uncertain. Among 61 individuals who underwent adenosine CMR stress testing before cardiac catheterization, we assessed the severity of coronary artery stenoses, mortality, the presence of stress and rest perfusion defects, as well as the presence of late gadolinium enhancement (LGE). Right ventricular stress-induced perfusion defects were positively associated with left anterior descending artery and proximal right coronary artery stenoses but were negatively associated with left circumflex artery stenoses. The presence of RVLGE was associated with mortality, but 77% of those with RVLGE also had left ventricular LGE. Proximal right coronary artery and left anterior descending artery stenoses are positively associated, whereas left circumflex artery stenoses are negatively associated with RV stress-induced perfusion defects. Right ventricular LGE was associated with mortality, but further study is needed to determine whether this is independent of left ventricular LGE.

MRI of normal and abnormal duodenum using Half-Fourier Single-Shot RARE and gadolinium-enhanced spoiled gradient echo sequences.

PubMed

Marcos, H B; Semelka, R C; Noone, T C; Woosley, J T; Lee, J K

1999-07-01

The objective of this research was two-fold: First, to describe the normal and abnormal MR appearances of the duodenum using combined Half-Fourier Acquisition Single Shot RARE (HASTE) and gadolinium-enhanced standard and fat suppressed spoiled gradient echo (SGE) sequences. The second objective was to assess the ability of these combined sequences to detect and characterize duodenal diseases. MR examinations were performed on fifty consecutive patients with no clinical history of duodenal diseases, who were 1) imaged with HASTE and gadolinium-enhanced standard and fat suppressed SGE sequences and 2) referred to MR examination for reasons other than duodenal diseases, and were reviewed retrospectively to determine the normal MR appearances of the duodenum. A second population of patients with abnormal duodenum who were imaged with the same MR sequences were included in the second part of this study. This population was composed of 20 consecutive patients with subsequently proven duodenal abnormalities, including: malrotation (2), diverticula (4), intussusception (1), sprue (1), polyps (2), neurofibroma (1), lymphoma (1), Zollinger Ellison syndrome (1), metastatic disease (1), Crohn's disease (1), and wall thickening and duodenitis (5). Normal measurements of the duodenum are described. Abnormalities of wall thickness and duodenal masses required combined HASTE and gadolinium-enhanced SGE images to evaluate well. Abnormalities of the bowel lumen (e.g., diverticula and intussusception), and developmental variants (e.g., malrotation), were sufficiently visualized on HASTE images alone. Bowel inflammation was best shown on gadolinium-enhanced fat suppressed SGE images. HASTE and gadolinium-enhanced fat suppressed SGE sequences are complementary techniques for the demonstration of normal and abnormal duodenum. The combined use of both sequences allows evaluation of different aspects of bowel diseases; abnormalities of position, lumen, and contents are well shown on HASTE, while inflammation is best shown on gadolinium enhanced fat suppressed SGE, and wall thickening and masses are best evaluated with the combined use of both techniques.

Subcellular SIMS imaging of gadolinium isotopes in human glioblastoma cells treated with a gadolinium containing MRI agent

NASA Astrophysics Data System (ADS)

Smith, Duane R.; Lorey, Daniel R.; Chandra, Subhash

2004-06-01

Neutron capture therapy is an experimental binary radiotherapeutic modality for the treatment of brain tumors such as glioblastoma multiforme. Recently, neutron capture therapy with gadolinium-157 has gained attention, and techniques for studying the subcellular distribution of gadolinium-157 are needed. In this preliminary study, we have been able to image the subcellular distribution of gadolinium-157, as well as the other six naturally abundant isotopes of gadolinium, with SIMS ion microscopy. T98G human glioblastoma cells were treated for 24 h with 25 mg/ml of the metal ion complex diethylenetriaminepentaacetic acid Gd(III) dihydrogen salt hydrate (Gd-DTPA). Gd-DTPA is a contrast enhancing agent used for MRI of brain tumors, blood-brain barrier impairment, diseases of the central nervous system, etc. A highly heterogeneous subcellular distribution was observed for gadolinium-157. The nuclei in each cell were distinctly lower in gadolinium-157 than in the cytoplasm. Even within the cytoplasm the gadolinium-157 was heterogeneously distributed. The other six naturally abundant isotopes of gadolinium were imaged from the same cells and exhibited a subcellular distribution consistent with that observed for gadolinium-157. These observations indicate that SIMS ion microscopy may be a viable approach for subcellular studies of gadolinium containing neutron capture therapy drugs and may even play a major role in the development and validation of new gadolinium contrast enhancing agents for diagnostic MRI applications.

Breakthrough reactions of iodinated and gadolinium contrast media after oral steroid premedication protocol.

PubMed

Jingu, Akiko; Fukuda, Junya; Taketomi-Takahashi, Ayako; Tsushima, Yoshito

2014-10-06

Adverse reactions to iodinated and gadolinium contrast media are an important clinical issue. Although some guidelines have proposed oral steroid premedication protocols to prevent adverse reactions, some patients may have reactions to contrast media in spite of premedication (breakthrough reaction; BTR).The purpose of this study was to assess the frequency, type and severity of BTR when following an oral steroid premedication protocol. All iodinated and gadolinium contrast-enhanced radiologic examinations between August 2011 and February 2013 for which the premedication protocol was applied in our institution were assessed for BTRs. The protocol was applied to a total of 252 examinations (153 patients, ages 15-87 years; 63 males, 90 females). Of these, 152 were for prior acute adverse reactions to contrast media, 85 were for a history of bronchial asthma, and 15 were for other reasons. There were 198 contrast enhanced CTs and 54 contrast enhanced MRIs. There were nine BTR (4.5%) for iodinated contrast media, and only one BTR (1.9%) for gadolinium contrast media: eight were mild and one was moderate. No patient who had a mild index reaction (IR) had a severe BTR. Incidence of BTRs when following the premedication protocol was low. This study by no means proves the efficacy of premedication, but provides some support for following a premedication protocol to improve safety of contrast-enhanced examinations when prior adverse reactions are mild, or when there is a history of asthma.

Breakthrough reactions of iodinated and gadolinium contrast media after oral steroid premedication protocol

PubMed Central

2014-01-01

Background Adverse reactions to iodinated and gadolinium contrast media are an important clinical issue. Although some guidelines have proposed oral steroid premedication protocols to prevent adverse reactions, some patients may have reactions to contrast media in spite of premedication (breakthrough reaction; BTR). The purpose of this study was to assess the frequency, type and severity of BTR when following an oral steroid premedication protocol. Methods All iodinated and gadolinium contrast-enhanced radiologic examinations between August 2011 and February 2013 for which the premedication protocol was applied in our institution were assessed for BTRs. Results The protocol was applied to a total of 252 examinations (153 patients, ages 15–87 years; 63 males, 90 females). Of these, 152 were for prior acute adverse reactions to contrast media, 85 were for a history of bronchial asthma, and 15 were for other reasons. There were 198 contrast enhanced CTs and 54 contrast enhanced MRIs. There were nine BTR (4.5%) for iodinated contrast media, and only one BTR (1.9%) for gadolinium contrast media: eight were mild and one was moderate. No patient who had a mild index reaction (IR) had a severe BTR. Conclusion Incidence of BTRs when following the premedication protocol was low. This study by no means proves the efficacy of premedication, but provides some support for following a premedication protocol to improve safety of contrast-enhanced examinations when prior adverse reactions are mild, or when there is a history of asthma. PMID:25287952

A New Approach in the Preparation of Dendrimer-Based Bifunctional Diethylenetriaminepentaacetic Acid MR Contrast Agent Derivatives

PubMed Central

Nwe, Kido; Xu, Heng; Regino, Celeste Aida S.; Bernardo, Marcelino; Ileva, Lilia; Riffle, Lisa; Wong, Karen J.; Brechbiel, Martin W.

2009-01-01

In this paper we report a new method to prepare and characterize a contrast agent based on a fourth-generation (G4) polyamidoamine (PAMAM) dendrimer conjugated to the gadolinium complex of the bifunctional diethylenetriamine pentaacetic acid derivative (1B4M-DTPA). The method involves pre-forming the metal-ligand chelate in alcohol prior to conjugation to the dendrimer. The dendrimer-based agent was purified by a Sephadex® G-25 column and characterized by elemental analysis. The analysis and SEHPLC data gave a chelate to dendrimer ratio of 30:1 suggesting conjugation at approximately every other amine terminal on the dendrimer. Molar relaxivity of the agent measured at pH 7.4 displayed a higher value than that of the analogous G4 dendrimer based agent prepared by the post-metal incorporation method (r1 = 26.9 vs. 13.9 mM-1s-1 at 3T and 22°C). This is hypothesized to be due to the higher hydrophobicity of this conjugate, and the lack of available charged carboxylate groups from non-complexed free ligands that might coordinate to the metal and thus also reduce water exchange sites. Additionally, the distribution populations of compounds that result from the post-metal incorporation route are eliminated from the current product simplifying characterization as quality control issues pertaining to the production of such agents for clinical use as MR contrast agents. In vivo imaging in mice showed a reasonably fast clearance (t1/2 = 24 min) suggesting a viable agent for use in clinical application. PMID:19555072

A new approach in the preparation of dendrimer-based bifunctional diethylenetriaminepentaacetic acid MR contrast agent derivatives.

PubMed

Nwe, Kido; Xu, Heng; Regino, Celeste Aida S; Bernardo, Marcelino; Ileva, Lilia; Riffle, Lisa; Wong, Karen J; Brechbiel, Martin W

2009-07-01

In this paper, we report a new method to prepare and characterize a contrast agent based on a fourth-generation (G4) polyamidoamine (PAMAM) dendrimer conjugated to the gadolinium complex of the bifunctional diethylenetriamine pentaacetic acid derivative (1B4M-DTPA). The method involves preforming the metal-ligand chelate in alcohol prior to conjugation to the dendrimer. The dendrimer-based agent was purified by a Sephadex G-25 column and characterized by elemental analysis. The analysis and SE-HPLC data gave a chelate to dendrimer ratio of 30:1 suggesting conjugation at approximately every other amine terminal on the dendrimer. Molar relaxivity of the agent measured at pH 7.4 displayed a higher value than that of the analogous G4 dendrimer based agent prepared by the postmetal incorporation method (r(1) = 26.9 vs 13.9 mM(-1) s(-1) at 3 T and 22 degrees C). This is hypothesized to be due to the higher hydrophobicity of this conjugate and the lack of available charged carboxylate groups from noncomplexed free ligands that might coordinate to the metal and thus also reduce water exchange sites. Additionally, the distribution populations of compounds that result from the postmetal incorporation route are eliminated from the current product simplifying characterization as quality control issues pertaining to the production of such agents for clinical use as MR contrast agents. In vivo imaging in mice showed a reasonably fast clearance (t(1/2) = 24 min) suggesting a viable agent for use in clinical application.

Effect of Iron Chelation Therapy on Glucose Metabolism in Non-Transfusion-Dependent Thalassaemia.

PubMed

Chuansumrit, Ampaiwan; Pengpis, Pimprae; Mahachoklertwattana, Pat; Sirachainan, Nongnuch; Poomthavorn, Preamrudee; Sungkarat, Witaya; Kadegasem, Praguywan; Khlairit, Patcharin; Wongwerawattanakoon, Pakawan

2017-01-01

To compare insulin sensitivity, β-cell function and iron status biomarkers in non-transfusion-dependent thalassaemia (NTDT) with iron excess during pre- and post-iron chelation. Subjects with NTDT, aged older than 10 years, with serum ferritin >300 ng/ml, were included. Iron chelation with deferasirox (10 mg/kg/day) was prescribed daily for 6 months. Ten patients with a median age of 17.4 years were enrolled. The comparison between pre- and post-chelation demonstrated significantly lower iron load: median serum ferritin (551.4 vs. 486.2 ng/ml, p = 0.047), median TIBC (211.5 vs. 233.5 µg/dl, p = 0.009) and median non-transferrin binding iron (5.5 vs. 1.4 µM, p = 0.005). All patients had a normal oral glucose tolerance test (OGTT) both pre- and post-chelation. However, fasting plasma glucose was significantly reduced after iron chelation (85.0 vs.79.5 mg/dl, p = 0.047). MRI revealed no significant changes of iron accumulation in the heart and liver after chelation, but there was a significantly lower iron load in the pancreas, assessed by higher T2* at post-chelation compared with pre-chelation (41.9 vs. 36.7 ms, p = 0.047). No adverse events were detected. A trend towards improving insulin sensitivity and β-cell function as well as a reduced pancreatic iron load was observed following 6 months of iron chelation (TCTR20160523003). © 2016 S. Karger AG, Basel.

Usefulness of the advanced neuroimaging protocol based on plain and gadolinium-enhanced constructive interference in steady state images for gamma knife radiosurgery and planning microsurgical procedures for skull base tumors.

PubMed

Hayashi, Motohiro; Chernov, Mikhail F; Tamura, Noriko; Yomo, Shoji; Tamura, Manabu; Horiba, Ayako; Izawa, Masahiro; Muragaki, Yoshihiro; Iseki, Hiroshi; Okada, Yoshikazu; Ivanov, Pavel; Régis, Jean; Takakura, Kintomo

2013-01-01

Gamma Knife radiosurgery (GKS) is currently performed with 0.1 mm preciseness, which can be designated microradiosurgery. It requires advanced methods for visualizing the target, which can be effectively attained by a neuroimaging protocol based on plain and gadolinium-enhanced constructive interference in steady state (CISS) images. Since 2003, the following thin-sliced images are routinely obtained before GKS of skull base lesions in our practice: axial CISS, gadolinium-enhanced axial CISS, gadolinium-enhanced axial modified time-of-flight (TOF), and axial computed tomography (CT). Fusion of "bone window" CT and magnetic resonance imaging (MRI), and detailed three-dimensional (3D) delineation of the anatomical structures are performed with the Leksell GammaPlan (Elekta Instruments AB). Recently, a similar technique has been also applied to evaluate neuroanatomy before open microsurgical procedures. Plain CISS images permit clear visualization of the cranial nerves in the subarachnoid space. Gadolinium-enhanced CISS images make the tumor "lucid" but do not affect the signal intensity of the cranial nerves, so they can be clearly delineated in the vicinity to the lesion. Gadolinium-enhanced TOF images are useful for 3D evaluation of the interrelations between the neoplasm and adjacent vessels. Fusion of "bone window" CT and MRI scans permits simultaneous assessment of both soft tissue and bone structures and allows 3D estimation and correction of MRI distortion artifacts. Detailed understanding of the neuroanatomy based on application of the advanced neuroimaging protocol permits performance of highly conformal and selective radiosurgical treatment. It also allows precise planning of the microsurgical procedures for skull base tumors.

Assessment of iron chelates efficiency for photo-Fenton at neutral pH.

PubMed

De Luca, Antonella; Dantas, Renato F; Esplugas, Santiago

2014-09-15

In this study, homogeneous photo-Fenton like at neutral pH was applied to remove sulfamethoxazole from water. The process was performed using different chelating agents in order to solubilize iron in a neutral water solution. The chelating agents tested were: ethylenediaminetetraacetic acid (EDTA); nitrilotriacetic acid (NTA); oxalic acid (OA) and tartaric acid (TA). The iron leaching was monitored over reaction time to evaluate the chelates stability and their resistance to HO· and UV-A radiation. Chelates of EDTA and NTA presented more stability than OA and TA, which also confirmed their higher efficiency. Total Organic Carbon (TOC) analyses were also performed to evaluate the contribution in terms of solution contamination related to the use of chelating agents. The better properties of biodegradability in respect of EDTA combined with better efficiency in terms of microcontaminant removal and the smallest TOC contribution indicate that NTA could represent a useful option to perform photo-Fenton processes at neutral pH. Copyright © 2014 Elsevier Ltd. All rights reserved.

Chelation in root canal therapy reconsidered.

PubMed

Zehnder, Matthias; Schmidlin, Patrick; Sener, Beatrice; Waltimo, Tuomas

2005-11-01

The aim of this study was to assess interactions of EDTA and citric acid (CA) with sodium hypochlorite (NaOCl), the indispensable endodontic irrigant. Other chelators were simultaneously evaluated as possible alternatives: sodium triphosphate (STP), amino tris methylenephosphonic acid (ATMA), and 1- hydroxyethylidene-1, 1-bisphosphonate (HEBP). Available chlorine was titrated in chelator-NaOCl solutions. All chelators other than HEBP and STP caused an almost complete, immediate loss of available chlorine in solution. Atomic absorbtion spectrometry and SEM evaluation of root canal walls of instrumented teeth indicated that NaOCl had no negative effect on calcium-complexing ability of chelators. STP was too weak a complexing agent to warrant further studies. Finally, CA-, EDTA-, and HEBP-NaOCl mixtures were evaluated for their antimicrobial capacity. Again, EDTA and CA negatively interfered with NaOCl, while HEBP did not.

Regional convection-enhanced delivery of gadolinium-labeled albumin in the rat hippocampus in vivo.

PubMed

Astary, Garrett W; Kantorovich, Svetlana; Carney, Paul R; Mareci, Thomas H; Sarntinoranont, Malisa

2010-03-15

Convection-enhanced delivery (CED) has emerged as a promising method of targeted drug delivery for treating central nervous system (CNS) disorders, but the influence of brain structure on infusate distribution is unclear. We have utilized this approach to study extracellular transport and distribution of a contrast agent in the hippocampus, a complex structure susceptible to CNS disorders. The magnetic resonance (MR) contrast agent diethylene triamene penta-acetic acid chelated gadolinium-labeled albumin (Gd-albumin), tagged with Evans blue dye, was directly infused (V(i)=5 microl) into the dorsal and ventral hippocampus of seven male Sprague-Dawley rats. The final distribution profile of the contrast agent, a product of CED and limited diffusion, was observed in vivo using high-resolution T1-weighted MR imaging at 11.1T. Dense cell layers, such as the granule cell layer of the dentate gyrus and the pyramidal cell layer of CA1, appeared to be barriers to transport of the tracer. Three-dimensional distribution shape and volume (V(d)) differences, between the dorsal and ventral hippocampus infusions, were determined from the MR images using a semi-automatic segmentation routine (dorsal V(d)=23.4+/-1.8 microl, ventral V(d)=36.4+/-5.1 microl). Finer structural detail of the hippocampus was obtained using a combination of histological analysis and fluorescence imaging. This study demonstrates that CED has the potential to target all regions of the hippocampus and that tracer distribution is influenced by infusion site, underlying structure and circuitry, and extent of backflow. Therefore, CED, combined with high-resolution MR imaging, may be a useful strategy for delivering therapeutics for the treatment of CNS disorders affecting the hippocampus. Published by Elsevier B.V.

Speciation and isotope dilution analysis of gadolinium-based contrast agents in wastewater.

PubMed

Telgmann, Lena; Wehe, Christoph A; Birka, Marvin; Künnemeyer, Jens; Nowak, Sascha; Sperling, Michael; Karst, Uwe

2012-11-06

The fate of Gadolinium (Gd)-based contrast agents for magnetic resonance imaging (MRI) during sewage treatment was investigated. The total concentration of Gd in influent and effluent 2 and 24 h composite samples was determined by means of isotope dilution analysis. The balancing of Gd input and output of a sewage plant over seven days indicated that approximately 10% of the Gd is removed during treatment. Batch experiments simulating the aeration tank of a sewage treatment plant confirmed the Gd complex removal during activated sludge treatment. For speciation analysis of the Gd complexes in wastewater samples, high performance liquid chromatography (HPLC) was hyphenated to inductively coupled plasma sector field mass spectrometry (ICP-SFMS). Separation of the five predominantly used contrast agents was carried out on a new hydrophilic interaction liquid chromatography stationary phase in less than 15 min. A limit of detection (LOD) of 0.13 μg/L and a limit of quantification of 0.43 μg/L could be achieved for the Gd chelates without having to apply enrichment techniques. Speciation analysis of the 24 h composite samples revealed that 80% of the Gd complexes are present as Gd-BT-DO3A in the sampled treatment plant. The day-of-week dependent variation of the complex load followed the variation of the total Gd load, indicating a similar behavior. The analysis of sewage sludge did not prove the presence of anthropogenic Gd. However, in the effluent of the chamber filter press, which was used for sludge dewatering, two of the contrast agents and three other unknown Gd species were observed. This indicates that species transformation took place during anaerobic sludge treatment.

MRI guided iron assessment and oral chelator use improve iron status in thalassemia major patients

PubMed Central

Nichols-Vinueza, Diana X.; White, Matthew T.; Powell, Andrew J.; Banka, Puja; Neufeld, Ellis J.

2017-01-01

Oral iron chelators and magnetic resonance imaging (MRI) assessment of heart and liver iron burden have become widely available since the mid 2000s, allowing for improved patient compliance with chelation and noninvasive monitoring of iron levels for titration of therapy. We evaluated the impact of these changes in our center for patients with thalassemia major and transfusional iron overload. This single center, retrospective observational study covered the period from 2005 through 2012. Liver iron content (LIC) was estimated both by a T2* method and by R2 (Ferriscan®) technique. Cardiac iron was assessed as cT2*. Forty-two patients (55% male) with transfused thalassemia and at least two MRIs were included (median age at first MRI, 17.5 y). Over a mean follow-up period of 5.2 ± 1.9 y, 190 MRIs were performed (median 4.5 per patient). Comparing baseline to last MRI, 63% of patients remained within target ranges for cT2* and LIC, and 13% improved from high values to the target range. Both the median LIC and cT2* (cR2* = 1000/cT2*) status improved over time: LIC 7.3 to 4.5 mg/g dry weight, P = 0.0004; cR2* 33.4 to 28.3 Hz, P = 0.01. Individual responses varied widely. Two patients died of heart failure during the study period. Annual MRI iron assessments and availability of oral chelators both facilitate changes in chelation dose and strategies to optimize care. PMID:24652616

Investigation of the usefulness of fluorescein sodium fluorescence in stereotactic brain biopsy.

PubMed

Thien, Ady; Han, Julian Xinguang; Kumar, Krishan; Ng, Yew Poh; Rao, Jai Prashanth; Ng, Wai Hoe; King, Nicolas Kon Kam

2018-02-01

Intraoperative frozen section assessment, to confirm acquisition of pathological tissues, is used in stereotactic brain biopsy to minimise sampling errors. Limitations include the dependence on dedicated neuro-oncology pathologists and an increase in operative duration. We investigated the use of intraoperative fluorescein sodium, and compared it to frozen section assessment, for confirming pathological tissue samples in the stereotactic biopsy of gadolinium-contrast-enhancing brain lesions. This prospective observational study consisted of 18 consecutive patients (12 men; median age, 63 years) who underwent stereotactic biopsy of gadolinium-contrast-enhancing brain lesions with intravenous fluorescein sodium administration. Twenty-three specimens were obtained and examined for the presence of fluorescence using a microscope with fluorescence visualisation capability. Positive and negative predictive values were calculated based on the fluorescence status of the biopsy samples with its corresponding intraoperative frozen section and definitive histopathological diagnosis. Nineteen specimens (83%) were fluorescent and four (17%) were non-fluorescent. All 19 fluorescent specimens were confirmed to be lesional on intraoperative frozen section assessment and were suitable for histopathological diagnosis. Three of the non-fluorescent specimens were confirmed to be lesional on intraoperative frozen section assessment. One non-fluorescent specimen was non-diagnostic on frozen section and histological assessments. The positive predictive value was 100% and the negative predictive value was 25%. Fluorescein sodium fluorescence is as accurate as frozen section assessment in confirming sampling of pathological tissue in the stereotactic biopsy of gadolinium-contrast-enhancing brain lesions. Fluorescein sodium fluorescence-guided stereotactic biopsy is a useful addition to the neurosurgical armamentarium.

Comparing potential copper chelation mechanisms in Parkinson's disease protein

NASA Astrophysics Data System (ADS)

Rose, Frisco; Hodak, Miroslav; Bernholc, Jerry

2011-03-01

We have implemented the nudged elastic band (NEB) as a guided dynamics framework for our real-space multigrid method of DFT-based quantum simulations. This highly parallel approach resolves a minimum energy pathway (MEP) on the energy hypersurface by relaxing intermediates in a chain-of-states. As an initial application we present an investigation of chelating agents acting on copper ion bound to α -synuclein, whose misfolding is implicated in Parkinson's disease (PD). Copper ions are known to act as highly effective misfolding agents in a-synuclein and are thus an important target in understanding PD. Furthermore, chelation therapy has shown promise in the treatment of Alzheimer's and other neuro-degenerative diseases with similar metal-correlated pathologies. At present, our candidate chelating agents include nicotine, curcumin and clioquinol. We examine their MEP activation barriers in the context of a PD onset mechanism to assess the viability of various chelators for PD remediation.

Quality-of-life outcomes with a disodium EDTA chelation regimen for coronary disease: results from the trial to assess chelation therapy randomized trial.

PubMed

Mark, Daniel B; Anstrom, Kevin J; Clapp-Channing, Nancy E; Knight, J David; Boineau, Robin; Goertz, Christine; Rozema, Theodore C; Liu, Diane M; Nahin, Richard L; Rosenberg, Yves; Drisko, Jeanne; Lee, Kerry L; Lamas, Gervasio A

2014-07-01

The National Institutes of Health.funded Trial to Assess Chelation Therapy (TACT) randomized 1708 stablecoronary disease patients aged .50 years who were .6 months post.myocardial infarction (2003.2010) to 40 infusions ofa multicomponent EDTA chelation solution or placebo. Chelation reduced the primary composite end point of mortality,recurrent myocardial infarction, stroke, coronary revascularization, or hospitalization for angina (hazard ratio, 0.82; 95%confidence interval, 0.69.0.99; P=0.035). In a randomly selected subset of 911 patients, we prospectively collected a battery of quality-of-life(QOL) instruments at baseline and at 6, 12, and 24 months after randomization. The prespecified primary QOL measures were the Duke Activity Status Index (Table I in the Data Supplement) and the Medical Outcomes Study Short-Form 36 Mental Health Inventory-5. All comparisons were by intention to treat. Baseline clinical and QOL variables were well balanced in the 451 patients randomized to chelation and in the 460 patients randomized to placebo. The Duke Activity Status Index improved in both groups during the first 6 months of therapy, but we found no evidence for a treatment-related difference (mean difference [chelation.placebo] during follow-up, 0.9 [95% confidence interval, .0.7 to 2.6; P=0.27]).There was no statistically significant evidence of a treatment-related difference in the Mental Health Inventory-5 during follow-up (mean difference, 1.0; 95% confidence interval, .0.1 to 2.0; P=0.08). None of the secondary QOL measures showed a consistent treatment-related difference. In stable, predominantly asymptomatic coronary disease patients with a history of myocardial infarction,EDTA chelation therapy did not have a detectable effect on QOL during 2 years of follow-up. URL: http://clinicaltrials.gov. Unique identifier: NCT00044213.

Use of gadolinium-based magnetic resonance imaging contrast agents and awareness of brain gadolinium deposition among pediatric providers in North America.

PubMed

Mithal, Leena B; Patel, Payal S; Mithal, Divakar; Palac, Hannah L; Rozenfeld, Michael N

2017-05-01

Numerous recent articles have reported brain gadolinium deposition when using linear but not macrocyclic gadolinium-based contrast agents (GBCAs). To determine the current landscape of gadolinium use among pediatric institutions and the knowledge base of radiologists and referring providers with regard to GBCAs and brain gadolinium deposition. We e-mailed voluntary closed surveys to 5,390 physicians in various pediatric professional societies between January 2016 and March 2016. We used chi-square and Fisher exact tests to compare response distributions among specialties. We found that 80% of surveyed pediatric hospitals use macrocyclic contrast agents. In the last year, 58% switched their agent, most commonly to gadoterate meglumine, with the most common reason being brain gadolinium deposition. Furthermore, surveys indicated that 23% of hospitals are considering switching, and, of these, 83% would switch to gadoterate meglumine; the most common reasons were brain gadolinium deposition and safety. Radiologists were more aware of brain gadolinium deposition than non-radiologist physicians (87% vs. 26%; P<0.0001). Radiologists and referring providers expressed similar levels of concern (95% and 89%). Twelve percent of radiologists and 2% of referring providers reported patients asking about brain gadolinium deposition. Radiologists were significantly more comfortable addressing patient inquiries than referring pediatric physicians (48% vs. 6%; P<0.0001). The number of MRIs requested by referring pediatric physicians correlated with their knowledge of brain gadolinium deposition, contrast agent used by their hospital, and comfort discussing brain gadolinium deposition with patients (P<0.0001). Since the discovery of brain gadolinium deposition, many pediatric hospitals have switched to or plan to switch to a more stable macrocyclic MR contrast agent, most commonly gadoterate meglumine. Despite this, there is need for substantial further education of radiologists and referring pediatric providers regarding GBCAs and brain gadolinium deposition.

Structural and magnetic phase transitions in gadolinium under high pressures and low temperatures

DOE PAGES

Samudrala, Gopi K.; Tsoi, Georgiy M.; Weir, Samuel T.; ...

2014-11-07

High pressure structural transition studies have been carried out on rare earth metal gadolinium in a diamond anvil cell at room temperature to 169 GPa. Gadolinium has been compressed to 38% of its initial volume at this pressure. With increasing pressure, a crystal structure sequence of hcp → Smtype→ dhcp → fcc → dfcc → monoclinic has been observed in our studies on gadolinium. The measured equation of state of gadolinium is presented to 169 GPa at ambient temperature. Magnetic ordering temperature of gadolinium has been studied using designer diamond anvils to a pressure of 25 GP and a temperaturemore » of 10 K. The magnetic ordering temperature has been determined from the four-point electrical resistivity measurements carried out on gadolinium. Furthermore, our experiments show that the magnetic transition temperature decreases with increasing pressure to 19 GPa and then increases when gadolinium is subjected to higher pressures.« less

Magnetic resonance characteristics and susceptibility weighted imaging of the brain in gadolinium encephalopathy.

PubMed

Samardzic, Dejan; Thamburaj, Krishnamoorthy

2015-01-01

To report the brain imaging features on magnetic resonance imaging (MRI) in inadvertent intrathecal gadolinium administration. A 67-year-old female with gadolinium encephalopathy from inadvertent high dose intrathecal gadolinium administration during an epidural steroid injection was studied with multisequence 3T MRI. T1-weighted imaging shows pseudo-T2 appearance with diffusion of gadolinium into the brain parenchyma, olivary bodies, and membranous labyrinth. Nulling of cerebrospinal fluid (CSF) signal is absent on fluid attenuation recovery (FLAIR). Susceptibility-weighted imaging (SWI) demonstrates features similar to subarachnoid hemorrhage. CT may demonstrate a pseudo-cerebral edema pattern given the high attenuation characteristics of gadolinium. Intrathecal gadolinium demonstrates characteristic imaging features on MRI of the brain and may mimic subarachnoid hemorrhage on susceptibility-weighted imaging. Identifying high dose gadolinium within the CSF spaces on MRI is essential to avoid diagnostic and therapeutic errors. Copyright © 2013 by the American Society of Neuroimaging.

Structural and magnetic phase transitions in gadolinium under high pressures and low temperatures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Samudrala, Gopi K.; Tsoi, Georgiy M.; Weir, Samuel T.

High pressure structural transition studies have been carried out on rare earth metal gadolinium in a diamond anvil cell at room temperature to 169 GPa. Gadolinium has been compressed to 38% of its initial volume at this pressure. With increasing pressure, a crystal structure sequence of hcp → Smtype→ dhcp → fcc → dfcc → monoclinic has been observed in our studies on gadolinium. The measured equation of state of gadolinium is presented to 169 GPa at ambient temperature. Magnetic ordering temperature of gadolinium has been studied using designer diamond anvils to a pressure of 25 GP and a temperaturemore » of 10 K. The magnetic ordering temperature has been determined from the four-point electrical resistivity measurements carried out on gadolinium. Furthermore, our experiments show that the magnetic transition temperature decreases with increasing pressure to 19 GPa and then increases when gadolinium is subjected to higher pressures.« less

Structural and magnetic phase transitions in gadolinium under high pressures and low temperatures

NASA Astrophysics Data System (ADS)

Samudrala, Gopi K.; Tsoi, Georgiy M.; Weir, Samuel T.; Vohra, Yogesh K.

2014-10-01

High pressure structural transition studies have been carried out on rare earth metal gadolinium in a diamond anvil cell at room temperature to 169 GPa. Gadolinium has been compressed to 38% of its initial volume at this pressure. With increasing pressure, a crystal structure sequence of hcp → Sm-type → dhcp → fcc → dfcc → monoclinic has been observed in our studies on gadolinium. The measured equation of state of gadolinium is presented to 169 GPa at ambient temperature. Magnetic ordering temperature of gadolinium has been studied using designer diamond anvils to a pressure of 25 GPa and a temperature of 10 K. The magnetic ordering temperature has been determined from the four-point electrical resistivity measurements carried out on gadolinium. Our experiments show that the magnetic transition temperature decreases with increasing pressure to 19 GPa and then increases when gadolinium is subjected to higher pressures.

Glyphosate, a chelating agent-relevant for ecological risk assessment?

PubMed

Mertens, Martha; Höss, Sebastian; Neumann, Günter; Afzal, Joshua; Reichenbecher, Wolfram

2018-02-01

Glyphosate-based herbicides (GBHs), consisting of glyphosate and formulants, are the most frequently applied herbicides worldwide. The declared active ingredient glyphosate does not only inhibit the EPSPS but is also a chelating agent that binds macro- and micronutrients, essential for many plant processes and pathogen resistance. GBH treatment may thus impede uptake and availability of macro- and micronutrients in plants. The present study investigated whether this characteristic of glyphosate could contribute to adverse effects of GBH application in the environment and to human health. According to the results, it has not been fully elucidated whether the chelating activity of glyphosate contributes to the toxic effects on plants and potentially on plant-microorganism interactions, e.g., nitrogen fixation of leguminous plants. It is also still open whether the chelating property of glyphosate is involved in the toxic effects on organisms other than plants, described in many papers. By changing the availability of essential as well as toxic metals that are bound to soil particles, the herbicide might also impact soil life, although the occurrence of natural chelators with considerably higher chelating potentials makes an additional impact of glyphosate for most metals less likely. Further research should elucidate the role of glyphosate (and GBH) as a chelator, in particular, as this is a non-specific property potentially affecting many organisms and processes. In the process of reevaluation of glyphosate its chelating activity has hardly been discussed.

Role of phenolics from Spondias pinnata bark in amelioration of iron overload induced hepatic damage in Swiss albino mice.

PubMed

Chaudhuri, Dipankar; Ghate, Nikhil Baban; Panja, Sourav; Mandal, Nripendranath

2016-07-26

Crude Spondias pinnata bark extract was previously assessed for its antioxidant, anticancer and iron chelating potentials. The isolated compounds gallic acid (GA) and methyl gallate (MG) were evaluated for their curative potential against iron overload-induced liver fibrosis and hepatocellular damage. In vitro iron chelation property and in vivo ameliorating potential from iron overload induced liver toxicity of GA and MG was assessed by different biochemical assays and histopathological studies. MG and GA demonstrated excellent reducing power activities but iron chelation potential of MG is better than GA. Oral MG treatment in mice displayed excellent efficacy (better than GA) to significantly restore the levels of liver antioxidants, serum markers and cellular reactive oxygen species in a dose-dependent fashion. Apart from these, MG exceptionally prevented lipid peroxidation and protein oxidation whereas GA demonstrated better activity to reduce collagen content, thereby strengthening its position as an efficient drug against hepatic damage/fibrosis, which was further supported by histopathological studies. Alongside, MG efficiently eliminated the cause of liver damage, i.e., excess iron, by chelating free iron and reducing the ferritin-bound iron. The present study confirmed the curative effect of GA and MG against iron overload hepatic damage via their potent antioxidant and iron-chelating potential.

Transfusional Iron Overload in a Cohort of Children with Sickle Cell Disease: Impact of Magnetic Resonance Imaging, Transfusion Method, and Chelation.

PubMed

Stanley, Helen M; Friedman, David F; Webb, Jennifer; Kwiatkowski, Janet L

2016-08-01

Transfusions prevent a number of complications of sickle cell disease (SCD), but cause inevitable iron loading. With magnetic resonance imaging (MRI), liver iron can be monitored noninvasively. Erythrocytapheresis can limit iron loading and oral chelation provides a more tolerable alternative to subcutaneous administration. The impact of these factors on control of iron burden in SCD has not been well studied. Iron monitoring practices, chelation use, and transfusion methods were assessed in our cohort of pediatric patients with SCD receiving chronic transfusion. The impact of these factors on iron burden was assessed. Among 84 subjects, the proportion that underwent appropriate liver iron concentration (LIC) assessment rose from 21% before to 81% after implementation of R2-MRI in 2006. Among subjects with at least two R2-MRI examinations, median LIC improved (13.2-7.9 mg/g dw, P = 0.027) from initial to final study. Most (67.9%) subjects initially received simple transfusions and subsequently transitioned to erythrocytapheresis. After switching, LIC improved from 13.1 to 4.3 mg/g dw (P < 0.001) after a median of 2.7 years and ferritin improved (2,471-392 ng/ml, P < 0.001) after a median of 4.2 years. Final serum ferritin and LIC correlated negatively with the proportion of transfusions administered by erythrocytapheresis and chelation adherence. Routine liver R2-MRI should be performed in individuals with SCD who receive chronic red cell transfusions. Adherence with chelation should be assessed regularly and erythrocytapheresis utilized when feasible to minimize iron loading or reduce iron stores accumulated during periods of simple transfusion. © 2016 Wiley Periodicals, Inc.

Chronic Toxic Metal Exposure and Cardiovascular Disease: Mechanisms of Risk and Emerging Role of Chelation Therapy.

PubMed

Aneni, Ehimen C; Escolar, Esteban; Lamas, Gervasio A

2016-12-01

Over the last few decades, there has been a growing body of epidemiologic evidence linking chronic toxic metal exposure to cardiovascular disease-related morbidity and mortality. The recent and unexpectedly positive findings from a randomized, double-blind, multicenter trial of metal chelation for the secondary prevention of atherosclerotic cardiovascular disease (Trial to Assess Chelation Therapy (TACT)) have focused the discussion on the role of chronic exposure to toxic metals in the development and propagation of cardiovascular disease and the role of toxic metal chelation therapy in the secondary prevention of cardiovascular disease. This review summarizes the most recent evidence linking chronic toxic metal exposure to cardiovascular disease and examines the findings of TACT.

Interventions for improving adherence to iron chelation therapy in people with sickle cell disease or thalassaemia

PubMed Central

Fortin, Patricia M; Madgwick, Karen V; Trivella, Marialena; Hopewell, Sally; Doree, Carolyn; Estcourt, Lise J

2016-01-01

This is the protocol for a review and there is no abstract. The objectives are as follows: To identify and assess the effectiveness of interventions to improve adherence to iron chelation therapy compared to standard care in people with SCD or thalassaemia including: identifying and assessing the effectiveness of different types of interventions (psychological and psychosocial, educational, medication interventions, or multi-component interventions);identifying and assessing the effectiveness of interventions specific to different age groups (children, adolescents, adults). PMID:27713668

Rationale for the Successful Management of EDTA Chelation Therapy in Human Burden by Toxic Metals

PubMed Central

2016-01-01

Exposure to environmental and occupational toxicants is responsible for adverse effects on human health. Chelation therapy is the only procedure able to remove toxic metals from human organs and tissue, aiming to treat damage related to acute and/or chronic intoxication. The present review focuses on the most recent evidence of the successful use of the chelating agent ethylenediaminetetraacetic acid (EDTA). Assessment of toxic-metal presence in humans, as well as the rationale of EDTA therapy in cardiovascular and neurodegenerative diseases, is reported. PMID:27896275

Design and Methodology of the Trial to Assess Chelation Therapy (TACT)

PubMed Central

Lamas, Gervasio A.; Goertz, Christine; Boineau, Robin; Mark, Daniel B.; Rozema, Theodore; Nahin, Richard L.; Drisko, Jeanne A.; Lee, Kerry L.

2011-01-01

The Trial to Assess Chelation Therapy (TACT) is an NIH-sponsored, randomized, double blind, placebo-controlled, 2×2 factorial clinical trial testing the benefits and risks of 40 infusions of a multi-component Na2EDTA-chelation solution compared with placebo, and of an oral, high-dose multivitamin and mineral supplement. TACT has randomized and will follow 1708 patients for an average of approximately 4 years. The primary endpoint is a composite of all cause mortality, myocardial infarction, stroke, coronary revascularization, and hospitalization for angina. A 900 patient substudy will examine quality of life outcomes. The trial is designed to have >85% power to detect a 25% relative reduction in the primary endpoint for each treatment factor. Enrollment began in September 2003 and completed in October 2010. PMID:22172430

Electrical and Structural Substrate of Arrhythmogenic Right Ventricular Cardiomyopathy Determined Using Noninvasive Electrocardiographic Imaging and Late Gadolinium Magnetic Resonance Imaging.

PubMed

Andrews, Christopher M; Srinivasan, Neil T; Rosmini, Stefania; Bulluck, Heerajnarain; Orini, Michele; Jenkins, Sharon; Pantazis, Antonis; McKenna, William J; Moon, James C; Lambiase, Pier D; Rudy, Yoram

2017-07-01

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a significant cause of sudden cardiac death in the young. Improved noninvasive assessment of ARVC and better understanding of the disease substrate are important for improving patient outcomes. We studied 20 genotyped ARVC patients with a broad spectrum of disease using electrocardiographic imaging (a method for noninvasive cardiac electrophysiology mapping) and advanced late gadolinium enhancement cardiac magnetic resonance scar imaging. Compared with 20 healthy controls, ARVC patients had longer ventricular activation duration (median, 52 versus 42 ms; P =0.007) and prolonged mean epicardial activation-recovery intervals (a surrogate for local action potential duration; median, 275 versus 241 ms; P =0.014). In these patients, we observed abnormal and varied epicardial activation breakthrough locations and regions of nonuniform conduction and fractionated electrograms. Nonuniform conduction and fractionated electrograms were present in the early concealed phase of ARVC. Electrophysiological abnormalities colocalized with late gadolinium enhancement scar, indicating a relationship with structural disease. Premature ventricular contractions were common in ARVC patients with variable initiation sites in both ventricles. Premature ventricular contraction rate increased with exercise, and within anatomic segments, it correlated with prolonged repolarization, electric markers of scar, and late gadolinium enhancement (all P <0.001). Electrocardiographic imaging reveals electrophysiological substrate properties that differ in ARVC patients compared with healthy controls. A novel mechanistic finding is the presence of repolarization abnormalities in regions where ventricular ectopy originates. The results suggest a potential role for electrocardiographic imaging and late gadolinium enhancement in early diagnosis and noninvasive follow-up of ARVC patients. © 2017 American Heart Association, Inc.

Liver acquisition with acceleration volume acquisition gadolinium-enhanced magnetic resonance combined with T2 sequences in the diagnosis of local recurrence of rectal cancer.

PubMed

Cao, Wuteng; Li, Fangqian; Gong, Jiaying; Liu, Dechao; Deng, Yanhong; Kang, Liang; Zhou, Zhiyang

2016-11-22

To investigate the efficacy of liver acquisition with acceleration volume acquisition (LAVA) gadolinium-enhanced magnetic resonance (MR) sequences and to assess its added accuracy in diagnosing local recurrence (LR) of rectal cancer with conventional T2-weighted fast spin echo (FSE) sequences. Pelvic MRI, including T2-weighted FSE sequences, gadolinium-enhanced sequences of LAVA and T1-weighted FSE with fat suppression, was performed on 225 patients with postoperative rectal cancer. Two readers evaluated the presence of LR according to "T2" (T2 sequences only), "T2 + LAVA-Gad" (LAVA and T2 imaging), and "T2 + T1-fs-Gad" (T1 fat suppression-enhanced sequence with T2 images). To evaluate diagnostic efficiency, imaging quality with LAVA and T1-fs-Gad by subjective scores and the signal intensity (SI) ratio. In the result, the SI ratio of LAVA was significantly higher than that of T1-fs-Gad (p = 0.0001). The diagnostic efficiency of "T2 + LAVA-Gad" was better than that of "T2 + T1-fs-Gad" (p = 0.0016 for Reader 1, p = 0.0001 for Reader 2) and T2 imaging only (p = 0.0001 for Reader 1; p = 0.0001 for Reader 2). Therefore, LAVA gadolinium-enhanced MR increases the accuracy of diagnosis of LR from rectal cancer and could replace conventional T1 gadolinium-enhanced sequences in the postoperative pelvic follow-up of rectal cancer.

Removal of gadolinium by peritoneal dialysis.

PubMed

Murashima, M; Drott, H R; Carlow, D; Shaw, L M; Milone, M; Bachman, M; Tsai, D E; Yang, S-L; Bloom, R D

2008-05-01

An association between gadolinium-containing contrast and the development of nephrogenic systemic fibrosis (NSF) has been increasingly recognized. For patients receiving hemodialysis (HD) who are exposed to gadolinium, the Federal Drug Administration (FDA) recommends HD to remove this contrast agent in order to minimize the risk of NSF. This study examines if gadolinium can be removed by frequent exchanges by peritoneal dialysis (PD). Following administration of 0.1 mmol/kg of gadodiamide to a patient with end-stage renal disease, the serum clearance of this contrast agent by automated PD was examined. 10 and 15 exchanges of PD using an automated cycler were respectively performed during the first and second 24-hour periods after gadolinium exposure. Serum gadolinium levels were measured 1 hour after the gadolinium administration, then at 24 and 48 hours after PD was initiated. 90% of the gadolinium was removed from the circulation in 2 days with a regimen of 10-15 exchanges per day of PD. For patients on chronic maintenance PD who receive gadolinium, our case suggests that a temporary intensive automated PD regimen, aimed at maximizing clearance of this contrast agent immediately after exposure, could be an effective alternative when institution of HD is problematic.

Neuroprotective effect of gadolinium: a stretch-activated calcium channel blocker in mouse model of ischemia-reperfusion injury.

PubMed

Gulati, Puja; Muthuraman, Arunachalam; Jaggi, Amteshwar S; Singh, Nirmal

2013-03-01

The present study was designed to investigate the potential of gadolinium, a stretch-activated calcium channel blocker in ischemic reperfusion (I/R)-induced brain injury in mice. Bilateral carotid artery occlusion of 12 min followed by reperfusion for 24 h was given to induce cerebral injury in male Swiss mice. Cerebral infarct size was measured using triphenyltetrazolium chloride staining. Memory was assessed using Morris water maze test and motor incoordination was evaluated using rota-rod, lateral push, and inclined beam walking tests. In addition, total calcium, thiobarbituric acid reactive substance (TBARS), reduced glutathione (GSH), and acetylcholinesterase (AChE) activity were also estimated in brain tissue. I/R injury produced a significant increase in cerebral infarct size. A significant loss of memory along with impairment of motor performance was also noted. Furthermore, I/R injury also produced a significant increase in levels of TBARS, total calcium, AChE activity, and a decrease in GSH levels. Pretreatment of gadolinium significantly attenuated I/R-induced infarct size, behavioral and biochemical changes. On the basis of the present findings, we can suggest that opening of stretch-activated calcium channel may play a critical role in ischemic reperfusion-induced brain injury and that gadolinium has neuroprotective potential in I/R-induced injury.

The ubiquitous DOTA and its derivatives: the impact of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid on biomedical imaging.

PubMed

Stasiuk, Graeme J; Long, Nicholas J

2013-04-07

Over the last twenty-five years 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) has made a significant impact on the field of diagnostic imaging. DOTA is not the only metal chelate in use in medical diagnostics, but it is the only one to significantly impact on all of the major imaging modalities Magnetic Resonance (MR), Positron Emission Tomography (PET), Single Photon Emission Computed Tomography (SPECT), and Fluorescence imaging. This crossover of modalities has been possible due to the versatility of DOTA firstly, to complex a variety of metal ions and secondly, the ease with which it can be modified for different disease states. This has driven research over the last two decades into the chemistry of DOTA and the modification of the substituent pendant arms of this macrocycle to create functional, targeted and dual-modal imaging agents. The primary use of DOTA has been with the lanthanide series of metals, gadolinium for MRI, europium and terbium for fluorescence and neodymium for near infra-red imaging. There are now many research groups dedicated to the use of lanthanides with DOTA although other chelates such as DTPA and NOTA are being increasingly employed. The ease with which DOTA can be conjugated to peptides has given rise to targeted imaging agents seen in the PET, SPECT and radiotherapy fields. These modalities use a variety of radiometals that complex with DOTA, e.g.(64)Cu and (68)Ga which are used in clinical PET scans, (111)In, and (90)Y for SPECT and radiotherapy. In this article, we will demonstrate the remarkable versatility of DOTA, how it has crossed the imaging modality boundaries and how it has been successfully transferred into the clinic.

Synthesis and evaluation of gadolinium complexes based on PAMAM as MRI contrast agents.

PubMed

Yan, Guo-Ping; Hu, Bin; Liu, Mai-Li; Li, Li-Yun

2005-03-01

Diethylenetriaminepentaacetic acid (DTPA) and pyridoxamine (PM) were incorporated into the amine groups on the surface of ammonia-core poly(amidoamine) dendrimers (PAMAM, Generation 2.0-5.0) to obtain dendritic ligands. These dendritic ligands were reacted with gadolinium chloride to yield the corresponding dendritic gadolinium (Gd) complexes. The dendritic ligands and their gadolinium complexes were characterized by(1)HNMR, IR, UV and elemental analysis. Relaxivity studies showed that the dendritic gadolinium complexes possessed higher relaxation effectiveness compared with the clinically used Gd-DTPA. After administration of the dendritic gadolinium complexes (0.09 mmol kg(-1) ) to rats, magnetic resonance imaging of the liver indicated that the dendritic gadolinium complexes containing pyridoxamine groups enhanced the contrast of the MR images of the liver, provided prolonged intravascular duration and produced highly contrasted visualization of blood vessels.

Biomolecular imaging of 13C-butyrate with dissolution-DNP: Polarization enhancement and formulation for in vivo studies

NASA Astrophysics Data System (ADS)

Flori, Alessandra; Giovannetti, Giulio; Santarelli, Maria Filomena; Aquaro, Giovanni Donato; De Marchi, Daniele; Burchielli, Silvia; Frijia, Francesca; Positano, Vincenzo; Landini, Luigi; Menichetti, Luca

2018-06-01

Magnetic Resonance Spectroscopy of hyperpolarized isotopically enriched molecules facilitates the non-invasive real-time investigation of in vivo tissue metabolism in the time-frame of a few minutes; this opens up a new avenue in the development of biomolecular probes. Dissolution Dynamic Nuclear Polarization is a hyperpolarization technique yielding a more than four orders of magnitude increase in the 13C polarization for in vivo Magnetic Resonance Spectroscopy studies. As reported in several studies, the dissolution Dynamic Nuclear Polarization polarization performance relies on the chemico-physical properties of the sample. In this study, we describe and quantify the effects of the different sample components on the dissolution Dynamic Nuclear Polarization performance of [1-13C]butyrate. In particular, we focus on the polarization enhancement provided by the incremental addition of the glassy agent dimethyl sulfoxide and gadolinium chelate to the formulation. Finally, preliminary results obtained after injection in healthy rats are also reported, showing the feasibility of an in vivo Magnetic Resonance Spectroscopy study with hyperpolarized [1-13C]butyrate using a 3T clinical set-up.

Synthesis and in vivo magnetic resonance imaging evaluation of biocompatible branched copolymer nanocontrast agents.

PubMed

Jackson, Alexander W; Chandrasekharan, Prashant; Shi, Jian; Rannard, Steven P; Liu, Quan; Yang, Chang-Tong; He, Tao

2015-01-01

Branched copolymer nanoparticles (D(h) =20-35 nm) possessing 1,4,7, 10-tetraazacyclododecane-N,N',N″,N‴-tetraacetic acid macrocycles within their cores have been synthesized and applied as magnetic resonance imaging (MRI) nanosized contrast agents in vivo. These nanoparticles have been generated from novel functional monomers via reversible addition-fragmentation chain transfer polymerization. The process is very robust and synthetically straightforward. Chelation with gadolinium and preliminary in vivo experiments have demonstrated promising characteristics as MRI contrast agents with prolonged blood retention time, good biocompatibility, and an intravascular distribution. The ability of these nanoparticles to perfuse and passively target tumor cells through the enhanced permeability and retention effect is also demonstrated. These novel highly functional nanoparticle platforms have succinimidyl ester-activated benzoate functionalities within their corona, which make them suitable for future peptide conjugation and subsequent active cell-targeted MRI or the conjugation of fluorophores for bimodal imaging. We have also demonstrated that these branched copolymer nanoparticles are able to noncovalently encapsulate hydrophobic guest molecules, which could allow simultaneous bioimaging and drug delivery.

Nanobiotechnology applications of reconstituted high density lipoprotein.

PubMed

Ryan, Robert O

2010-12-01

High-density lipoprotein (HDL) plays a fundamental role in the Reverse Cholesterol Transport pathway. Prior to maturation, nascent HDL exist as disk-shaped phospholipid bilayers whose perimeter is stabilized by amphipathic apolipoproteins. Methods have been developed to generate reconstituted (rHDL) in vitro and these particles have been used in a variety of novel ways. To differentiate between physiological HDL particles and non-natural rHDL that have been engineered to possess additional components/functions, the term nanodisk (ND) is used. In this review, various applications of ND technology are described, such as their use as miniature membranes for solubilization and characterization of integral membrane proteins in a native like conformation. In other work, ND harboring hydrophobic biomolecules/drugs have been generated and used as transport/delivery vehicles. In vitro and in vivo studies show that drug loaded ND are stable and possess potent biological activity. A third application of ND is their use as a platform for incorporation of amphiphilic chelators of contrast agents, such as gadolinium, used in magnetic resonance imaging. Thus, it is demonstrated that the basic building block of plasma HDL can be repurposed for alternate functions.

Chemistry of carcinogenic metals.

PubMed Central

Martell, A E

1981-01-01

The periodic distribution of known and suspected carcinogenic metal ions is described, and the chemical behavior of various types of metal ions is explained in terms of the general theory of hard and soft acids and bases. The chelate effect is elucidated, and the relatively high stability of metal chelates in very dilute solutions is discussed. The concepts employed for the chelate effect are extended to explain the high stabilities of macrocyclic and cryptate complexes. Procedures for the use of equilibrium data to determine the speciation of metal ions and complexes under varying solution conditions are described. Methods for assessing the interferences by hydrogen ion, competing metal ions, hydrolysis, and precipitation are explained, and are applied to systems containing iron(III) chelates of fourteen chelating agents designed for effective binding of the ferric ion. The donor groups available for the building up of multidentate ligands are presented, and the ways in which they may be combined to achieve high affinity and selectivity for certain types of metal ions are explained. PMID:6791915

Thermodynamic properties of gadolinium in Ga-Sn and Ga-Zn eutectic based alloys

NASA Astrophysics Data System (ADS)

Maltsev, Dmitry S.; Volkovich, Vladimir A.; Yamshchikov, Leonid F.; Chukin, Andrey V.

2016-09-01

Thermodynamic properties of gadolinium in Ga-Sn and Ga-Zn eutectic based alloys were studied. Temperature dependences of gadolinium activity in the studied alloys were determined at 573-1073 K employing the EMF method. Solubility of gadolinium in the Ga-Sn and Ga-Zn alloys was measured at 462-1073 K using IMCs sedimentation method. Activity coefficients as well as partial and excess thermodynamic functions of gadolinium in the studied alloys were calculated on the basis of the obtained experimental data.

Spectral presaturation inversion recovery MR imaging sequence after gadolinium injection to differentiate fibrotic scar tissue and neoplastic strands in the mesorectal fat in patients undergoing restaging of rectal carcinoma after neoadjuvant chemo- and radiation therapy.

PubMed

Quaia, Emilio; Ulcigrai, Veronica; Coss, Matteo; De Paoli, Luca; Ukmar, Maja; Zanconati, Fabrizio; De Pellegrin, Alessandro; De Manzini, Nicolò; Cova, Maria Assunta

2011-11-01

To retrospectively assess the value of spectral presaturation by inversion-recovery (SPIR) magnetic resonance (MR) imaging sequence after gadolinium injection to differentiate fibrotic scar tissue and tumoral infiltration within the mesorectal fat in patients with rectal carcinoma undergoing MR restaging after neoadjuvant chemo- and radiation therapy (CRT). Forty-three consecutive patients (mean age, 65.8 years; range, 46-85 years; male:female, 29:14) with locally advanced rectal carcinoma underwent CRT followed by surgery. MR imaging was performed before and after completion of CRT by using T2-weighted turbo spin-echo and T1-weighted SPIR sequences before and after gadolinium injection, and MR images were assessed by two radiologists in consensus. Logistic regression was conducted to test the significance of the MR image findings with histology. After CRT the disease was either limited to the rectal wall (n = 18 patients) or presented perirectal infiltration (n = 25) on histology. In 21 patients, mesorectal enhancing strands were observed. Reticular-shaped enhancing strands reaching the mesorectal fascia presented the highest correlation with tumor infiltration of the mesorectal fat (OR 130.33, 95% CI: 4.1-4220.29; logistic regression), whereas linear-shaped enhancing strands either reaching or not reaching the mesorectal fascia (OR 0.25 or 0.1, 95% CI: 0.024-2.6 or 0.01-1.07) revealed the lowest correlation. Reticular-shaped enhancing strands on SPIR MR imaging after gadolinium injection are associated with tumor infiltration of the mesorectal fat. Copyright © 2011 AUR. Published by Elsevier Inc. All rights reserved.

Gadolinium diethylenetriaminopentaacetic acid-loaded chitosan microspheres for gadolinium neutron-capture therapy.

PubMed

Saha, Tapan Kumar; Ichikawa, Hideki; Fukumori, Yoshinobu

2006-12-11

In order to provide a suitable device that would contain water-soluble drugs, highly water-soluble gadolinium diethylenetriaminopentaacetic acid-loaded chitosan microspheres (CMS-Gd-DTPA) were prepared by the emulsion method using glutaraldehyde as a cross-linker and Span 80 as a surfactant for gadolinium neutron-capture therapy of cancer. The gadolinium content and the mass median diameter of CMS-Gd-DTPA were estimated. The size and morphology of the CMS-Gd-DTPA were strongly influenced by the initial applied weight ratio of Gd-DTPA:chitosan. FTIR spectra showed that the electrostatic interaction between chitosan and Gd-DTPA accelerated the formation of gadolinium-enriched chitosan microspheres. Sufficient amounts of glutaraldehyde and Span 80 were necessary for producing discrete CMS-Gd-DTPA. The CMS-Gd-DTPA having a mass median diameter 11.7microm and 11.6% of gadolinium could be used in Gd-NCT following intratumoral injection.

Phytoextraction of heavy metals from contaminated soil by co-cropping with chelator application and assessment of associated leaching risk.

PubMed

Wei, Z B; Guo, X F; Wu, Q T; Long, X X; Penn, C J

2011-08-01

Phytoextraction using hyperaccumulating plants is generally time-consuming and requires the cessation of agriculture. We coupled chelators and a co-cropping system to enhance phytoextraction rates, while allowing for agricultural production. An experiment on I m3 lysimeter beds was conducted with a co-cropping system consisting of the hyperaccumulator Sedum alfredii and low-accumulating corn (Zea Mays, cv. Huidan-4), with addition ofa mixture of chelators (MC), to assess the efficiency of chelator enhanced co-crop phytoextraction and the leaching risk caused by the chelator. The results showed that the addition of MC promoted the growth of S. alfredii in the first crop (spring-summer season) and significantly increased the metal phytoextraction. The DTPA-extractable and total metal concentrations in the topsoil were also reduced more significantly with the addition of MC compared with the control treatments. However, mono-cropped S. alfredii without MC was more suitable for maximizing S. alfredii growth and therefore phytoextraction of Zn and Cd during the autumn-winter seasons. No adverse impact to groundwater due to MC application was observed during the experiments with three crops and three MC applications. But elevated total Cd and Pb concentrations among subsoils compared to the initial subsoil concentrations were found for the co-crop + MC treatment after the third crop.

Nephrogenic Systemic Fibrosis Manifesting a Decade After Exposure to Gadolinium.

PubMed

Larson, Krista N; Gagnon, Amy L; Darling, Melissa D; Patterson, James W; Cropley, Thomas G

2015-10-01

Nephrogenic systemic fibrosis (NSF) is a fibrosing skin disorder that develops in patients with kidney failure and has been linked to exposure to gadolinium-containing contrast agents. The time between exposure to gadolinium and the initial presentation of NSF is typically weeks to months but has been documented to be as long as 3½ years. We report a case of NSF developing 10 years after exposure to gadolinium. A long-term hemodialysis patient was exposed to gadolinium several times between 1998 and 2004 during magnetic resonance angiography of his abdominal vessels and arteriovenous fistula. In 2014, he was seen at our clinic with new dermal papules and plaques. Biopsy of affected skin showed thickening of collagen, CD34+ spindle cells, and increased mucin in the dermis, supporting the diagnosis of NSF. The clinical history and histopathological features of this case support the diagnosis of NSF 10 years after exposure to gadolinium. Although the use of gadolinium contrast agents in patients with kidney failure has markedly decreased, patients with exposure to gadolinium years to decades previously may manifest the disease.

Increased Uptake of Chelated Copper Ions by Lolium perenne Attributed to Amplified Membrane and Endodermal Damage

PubMed Central

Johnson, Anthea; Singhal, Naresh

2015-01-01

The contributions of mechanisms by which chelators influence metal translocation to plant shoot tissues are analyzed using a combination of numerical modelling and physical experiments. The model distinguishes between apoplastic and symplastic pathways of water and solute movement. It also includes the barrier effects of the endodermis and plasma membrane. Simulations are used to assess transport pathways for free and chelated metals, identifying mechanisms involved in chelate-enhanced phytoextraction. Hypothesized transport mechanisms and parameters specific to amendment treatments are estimated, with simulated results compared to experimental data. Parameter values for each amendment treatment are estimated based on literature and experimental values, and used for model calibration and simulation of amendment influences on solute transport pathways and mechanisms. Modeling indicates that chelation alters the pathways for Cu transport. For free ions, Cu transport to leaf tissue can be described using purely apoplastic or transcellular pathways. For strong chelators (ethylenediaminetetraacetic acid (EDTA) and diethylenetriaminepentaacetic acid (DTPA)), transport by the purely apoplastic pathway is insufficient to represent measured Cu transport to leaf tissue. Consistent with experimental observations, increased membrane permeability is required for simulating translocation in EDTA and DTPA treatments. Increasing the membrane permeability is key to enhancing phytoextraction efficiency. PMID:26512647

Chelation therapy to prevent diabetes-associated cardiovascular events.

PubMed

Diaz, Denisse; Fonseca, Vivian; Aude, Yamil W; Lamas, Gervasio A

2018-05-24

For over 60 years, chelation therapy with disodium ethylene diamine tetraacetic acid (EDTA, edetate) had been used for the treatment of cardiovascular disease (CVD) despite lack of scientific evidence for efficacy and safety. The Trial to Assess Chelation Therapy (TACT) was developed and received funding from the National Institutes of Health (NIH) to ascertain the safety and efficacy of chelation therapy in patients with CVD. This pivotal trial demonstrated an improvement in outcomes in postmyocardial infarction (MI) patients. Interestingly, it also showed a particularly large reduction in CVD events and all-cause mortality in the prespecified subgroup of patients with diabetes. The TACT results may support the concept of metal chelation to reduce metal-catalyzed oxidation reactions that promote the formation of advanced glycation end products, a precursor of diabetic atherosclerosis. In this review, we summarize the epidemiological and basic evidence linking toxic metal accumulation and diabetes-related CVD, supported by the salutary effects of chelation in TACT. If the ongoing NIH-funded TACT2, in diabetic post-MI patients, proves positive, this unique therapy will enter the armamentarium of endocrinologists and cardiologists seeking to reduce the atherosclerotic risk of their diabetic patients.

Structural, optical and magnetic properties of gadolinium sesquioxide nanobars synthesized via thermal decomposition of gadolinium oxalate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Manigandan, R.; Giribabu, K.; Suresh, R.

2013-10-15

Graphical abstract: - Highlights: • The cubic Gd{sub 2}O{sub 3} nanobars are synthesized by decomposition of C{sub 6}H{sub 20}Gd{sub 2}O{sub 22}. • The nanoparticles are rectangular bar shape with high porous surface. • The combination of magnetic and optical properties within a single particle. • The Gd{sub 2}O{sub 3} nanobars have tailorable nanostructure, wide bandgap and are paramagnetic. - Abstract: Gadolinium oxide nanobars were obtained by thermal decomposition of gadolinium oxalate, which was synthesized by the chemical precipitation method along with glycerol. The functional group analysis and formation of gadolinium oxide from gadolinium oxalate were characterized by the Fourier transformmore » infrared spectroscopy and thermo gravimetric analyzer. The crystal structure, average crystallite size, and lattice parameter were analyzed by X-ray diffraction technique. Moreover, Raman shifts, elemental composition and morphology of the gadolinium oxide was widely investigated by the laser Raman microscope, X-ray photoelectron spectroscopy, FE-SEM-EDAX and HR-TEM, respectively. Furthermore, the optical properties like band gap, absorbance measurement of the gadolinium oxide were extensively examined. In addition, the paramagnetic property of gadolinium oxide nanobars was explored by the vibrating sample magnetometer.« less

Pediatric Patients Demonstrate Progressive T1-Weighted Hyperintensity in the Dentate Nucleus following Multiple Doses of Gadolinium-Based Contrast Agent.

PubMed

Roberts, D R; Chatterjee, A R; Yazdani, M; Marebwa, B; Brown, T; Collins, H; Bolles, G; Jenrette, J M; Nietert, P J; Zhu, X

2016-12-01

While there have been recent reports of brain retention of gadolinium following gadolinium-based contrast agent administration in adults, a retrospective series of pediatric patients has not previously been reported, to our knowledge. We investigated the relationship between the number of prior gadolinium-based contrast agent doses and increasing T1 signal in the dentate nucleus on unenhanced T1-weighted MR imaging. We hypothesized that despite differences in pediatric physiology and the smaller gadolinium-based contrast agent doses that pediatric patients are typically administered based on weighted-adjusted dosing, the pediatric brain would also demonstrate dose-dependent increasing T1 signal in the dentate nucleus. We included children with multiple gadolinium-based contrast agent administrations at our institution. A blinded reader placed ROIs within the dentate nucleus and adjacent cerebellar white matter. To eliminate reader bias, we also performed automated ROI delineation of the dentate nucleus, cerebellar white matter, and pons. Dentate-to-cerebellar white matter and dentate-to pons ratios were compared with the number of gadolinium-based contrast agent administrations. During 20 years at our institution, 280 patients received at least 5 gadolinium-based contrast agent doses, with 1 patient receiving 38 doses. Sixteen patients met the inclusion/exclusion criteria for ROI analysis. Blinded reader dentate-to-cerebellar white matter ratios were significantly associated with gadolinium-based contrast agent doses (r s = 0.77, P = .001). The dentate-to-pons ratio and dentate-to-cerebellar white matter ratios based on automated ROI placement were also significantly correlated with gadolinium-based contrast agent doses (t = 4.98, P < .0001 and t = 2.73, P < .02, respectively). In pediatric patients, the number of prior gadolinium-based contrast agent doses is significantly correlated with progressive T1-weighted dentate hyperintensity. Definitive confirmation of gadolinium deposition requires tissue analysis. Any potential clinical sequelae of gadolinium retention in the developing brain are unknown. Given this uncertainty, we suggest taking a cautious stance, including the use, in pediatric patients, of higher stability, macrocyclic agents, which in both human and animal studies have been shown to be associated with lower levels of gadolinium deposition, and detailed documentation of dosing. Most important, a patient should not be deprived of a well-indicated contrasted MR examination. © 2016 by American Journal of Neuroradiology.

Defining serum ferritin thresholds to predict clinically relevant liver iron concentrations for guiding deferasirox therapy when MRI is unavailable in patients with non-transfusion-dependent thalassaemia.

PubMed

Taher, Ali T; Porter, John B; Viprakasit, Vip; Kattamis, Antonis; Chuncharunee, Suporn; Sutcharitchan, Pranee; Siritanaratkul, Noppadol; Origa, Raffaella; Karakas, Zeynep; Habr, Dany; Zhu, Zewen; Cappellini, Maria Domenica

2015-01-01

Liver iron concentration (LIC) assessment by magnetic resonance imaging (MRI) remains the gold standard to diagnose iron overload and guide iron chelation therapy in patients with non-transfusion-dependent thalassaemia (NTDT). However, limited access to MRI technology and expertise worldwide makes it practical to also use serum ferritin assessments. The THALASSA (assessment of Exjade(®) in non-transfusion-dependent THALASSemiA patients) study assessed the efficacy and safety of deferasirox in iron-overloaded NTDT patients and provided a large data set to allow exploration of the relationship between LIC and serum ferritin. Using data from screened patients and those treated with deferasirox for up to 2 years, we identified clinically relevant serum ferritin thresholds (for when MRI is unavailable) for the initiation of chelation therapy (>800 μg/l), as well as thresholds to guide chelator dose interruption (<300 μg/l) and dose escalation (>2000 μg/l). (clinicaltrials.gov identifier: NCT00873041). © 2014 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd.

Chelation therapy and cardiovascular disease: connecting scientific silos to benefit cardiac patients.

PubMed

Peguero, Julio G; Arenas, Ivan; Lamas, Gervasio A

2014-08-01

Medical practitioners have treated atherosclerotic disease with chelation therapy for over 50 years. Lack of strong of evidence led conventional practitioners to abandon its use in the 1960s and 1970s. This relegated chelation therapy to complementary and alternative medicine practitioners, who reported good anecdotal results. Concurrently, the epidemiologic evidence linking xenobiotic metals with cardiovascular disease and mortality gradually accumulated, suggesting a plausible role for chelation therapy. On the basis of the continued use of chelation therapy without an evidence base, the National Institutes of Health released a Request for Applications for a definitive trial of chelation therapy. The Trial to Assess Chelation Therapy (TACT) was formulated as a 2 × 2 factorial randomized controlled trial of intravenous EDTA-based chelation vs. placebo and high-dose oral multivitamins and multiminerals vs. oral placebo. The composite primary endpoint was death, reinfarction, stroke, coronary revascularization, or hospitalization for angina. A total of 1708 post-MI patients who were 50 years or older with a creatinine of 2.0 or less were enrolled and received 55,222 infusions of disodium EDTA or placebo with a median follow-up of 55 months. Patients were on evidence-based post-MI medications including statins. EDTA proved to be safe. EDTA chelation therapy reduced cardiovascular events by 18%, with a 5-year number needed to treat (NNT) of 18. Prespecified subgroup analysis revealed a robust benefit in patients with diabetes mellitus with a 41% reduction in the primary endpoint (5-year NNT = 6.5), and a 43% 5-year relative risk reduction in all-cause mortality (5-year NNT = 12). The magnitude of benefit is such that it suggests urgency in replication and implementation, which could, due to the excellent safety record, occur simultaneously. Copyright © 2014 Elsevier Inc. All rights reserved.

Delayed enhancement cardiac computed tomography for the assessment of myocardial infarction: from bench to bedside

PubMed Central

2017-01-01

A large number of studies support the increasingly relevant prognostic value of the presence and extent of delayed enhancement (DE), a surrogate marker of fibrosis, in diverse etiologies. Gadolinium and iodinated based contrast agents share similar kinetics, thus leading to comparable myocardial characterization with cardiac magnetic resonance (CMR) and cardiac computed tomography (CT) at both first-pass perfusion and DE imaging. We review the available evidence of DE imaging for the assessment of myocardial infarction (MI) using cardiac CT (CTDE), from animal to clinical studies, and from 16-slice CT to dual-energy CT systems (DECT). Although both CMR and gadolinium agents have been originally deemed innocuous, a number of concerns (though inconclusive and very rare) have been recently issued regarding safety issues, including DNA double-strand breaks related to CMR, and gadolinium-associated nephrogenic systemic fibrosis and deposition in the skin and certain brain structures. These concerns have to be considered in the context of non-negligible rates of claustrophobia, increasing rates of patients with implantable cardiac devices, and a number of logistic drawbacks compared with CTDE, such as higher costs, longer scanning times, and difficulties to scan patients with impaired breath-holding capabilities. Overall, these issues might encourage the role of CTDE as an alternative for DE-CMR in selected populations. PMID:28540211

Pathophysiology of gadolinium-associated systemic fibrosis

PubMed Central

Drel, Viktor; Gorin, Yves

2016-01-01

Systemic fibrosis from gadolinium-based magnetic resonance imaging contrast is a scourge for the afflicted. Although gadolinium-associated systemic fibrosis is a rare condition, the threat of litigation has vastly altered clinical practice. Most theories concerning the etiology of the fibrosis are grounded in case reports rather than experiment. This has led to the widely accepted conjecture that the relative affinity of certain contrast agents for the gadolinium ion inversely correlates with the risk of succumbing to the disease. How gadolinium-containing contrast agents trigger widespread and site-specific systemic fibrosis and how chronicity is maintained are largely unknown. This review highlights experimentally-derived information from our laboratory and others that pertain to our understanding of the pathophysiology of gadolinium-associated systemic fibrosis. PMID:27147669

Self-Assembly of Peptide Amphiphiles Designed as Imaging Probes for 19F and Relaxation-Enhanced 1H imaging

NASA Astrophysics Data System (ADS)

Preslar, Adam Truett

This work incorporates whole-body imaging functionality into peptide amphiphile (PA) nanostructures used for regenerative medicine to facilitate magnetic resonance imaging (MRI). Two strategies were employed: 1. Conjugation of gadolinium chelates to peptide nanostructures to monitor biomaterial degradation in vivo with MRI and inductively-coupled plasma-mass spectroscopy (ICP-MS) 2. Synthesis of perfluorinated moiety-bearing peptide amphiphiles for 19F-MRI. The Gd(III) chelate gadoteridol was conjugated by copper-catalyzed "click" chemistry to a series of PAs known to form cylindrical nanostructures. By fitting nuclear magnetic resonance dispersion (NMRD) profiles to the Solomon-Bloembergen-Morgan (SBM) equations, it was observed that the water exchange parameter (tauM) depended on thermal annealing or calcium ion cross-linking. The sequence C16V 3A3E3G(Gd) exhibited an acceleration of nearly 100 ns after thermal annealing and calcium addition. These gadolinium-labeled PAs were used to track in vivo degradation of gels within the tibialis anterior muscle in a murine model. The half-life of biomaterial degradation was determined to be 13.5 days by inductively coupled plasma mass spectrometry (ICP-MS) of Gd(III). Gel implants could be monitored by MRI for eight days before the signal dispersed due to implant degradation and dilution. Additionally, nanostructures incorporating highly fluorinated domains were investigated for use as MRI contrast agents. Short, perfluoroalkyane tails of seven or eight carbon atoms in length were grafted to PA sequences containing a V2A2 beta-sheet forming sequence. The V2A2 sequence is known to drive 1D nanostructure assembly. It was found that the sequences C7F13V2A 2E2 and C7F13V2A 2K3 formed 1D assemblies in water which transition from ribbon-like to cylindrical shape as pH increases from 4.5 to 8.0. Ribbon-like nanostructures had reduced magnetic resonance signal by T 2 relaxation quenching, whereas their cylindrical counterparts exhibited strong signals with signal-to-noise ratios greater than 100. In addition to pH, the effect of divalent calcium ions on NMR signal was probed. C7 V2A2E2 was shown to exhibit the highest sensitivity to calcium in the 1.5 to 6 mM regime. This range corresponded to widening of the C7V2A2E2 nanostructure from 16+/-4 to 22+/-5 nm. It is speculated that increasing ribbon thickness is tied to magnetic resonance signal quenching due to higher local viscosity of the perfluorinated moiety.

Enhancements in hepatobiliary imaging: the spectrum of gadolinium-ethoxybenzyl diethylenetriaminepentaacetic acid usages in hepatobiliary magnetic resonance imaging.

PubMed

Channual, Stephanie; Pahwa, Anokh; Lu, David S; Raman, Steven S

2016-09-01

Gadolinium-ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA) is a unique hepatocyte-specific contrast agent approved for clinical use in the United States in 2008. Gd-EOB-DTPA-enhanced MR has shown to improve detection and characterization of hepatic lesions. Gd-EOB-DTPA is now being routinely used in daily clinical practice worldwide. Therefore, it is important for radiologists to be familiar with the potential uses and pitfalls of Gd-EOB-DTPA, which extends beyond the assessment of focal hepatic lesions. The purpose of this article is to review the various usages of Gd-EOB-DTPA in hepatobiliary MR imaging.

MRI with intrathecal MRI gadolinium contrast medium administration: a possible method to assess glymphatic function in human brain.

PubMed

Eide, Per Kristian; Ringstad, Geir

2015-11-01

Recently, the "glymphatic system" of the brain has been discovered in rodents, which is a paravascular, transparenchymal route for clearance of excess brain metabolites and distribution of compounds in the cerebrospinal fluid. It has already been demonstrated that intrathecally administered gadolinium (Gd) contrast medium distributes along this route in rats, but so far not in humans. A 27-year-old woman underwent magnetic resonance imaging (MRI) with intrathecal administration of gadobutrol, which distributed throughout her entire brain after 1 and 4.5 h. MRI with intrathecal Gd may become a tool to study glymphatic function in the human brain.

Saline as the Sole Contrast Agent for Successful MRI-guided Epidural Injections

DOE Office of Scientific and Technical Information (OSTI.GOV)

Deli, Martin, E-mail: martin.deli@web.de; Fritz, Jan, E-mail: jfritz9@jhmi.edu; Mateiescu, Serban, E-mail: mateiescu@microtherapy.de

Purpose. To assess the performance of sterile saline solution as the sole contrast agent for percutaneous magnetic resonance imaging (MRI)-guided epidural injections at 1.5 T. Methods. A retrospective analysis of two different techniques of MRI-guided epidural injections was performed with either gadolinium-enhanced saline solution or sterile saline solution for documentation of the epidural location of the needle tip. T1-weighted spoiled gradient echo (FLASH) images or T2-weighted single-shot turbo spin echo (HASTE) images visualized the test injectants. Methods were compared by technical success rate, image quality, table time, and rate of complications. Results. 105 MRI-guided epidural injections (12 of 105 withmore » gadolinium-enhanced saline solution and 93 of 105 with sterile saline solution) were performed successfully and without complications. Visualization of sterile saline solution and gadolinium-enhanced saline solution was sufficient, good, or excellent in all 105 interventions. For either test injectant, quantitative image analysis demonstrated comparable high contrast-to-noise ratios of test injectants to adjacent body substances with reliable statistical significance levels (p < 0.001). The mean table time was 22 {+-} 9 min in the gadolinium-enhanced saline solution group and 22 {+-} 8 min in the saline solution group (p = 0.75). Conclusion. Sterile saline is suitable as the sole contrast agent for successful and safe percutaneous MRI-guided epidural drug delivery at 1.5 T.« less

Gadolinium prevents high airway pressure-induced permeability increases in isolated rat lungs.

PubMed

Parker, J C; Ivey, C L; Tucker, J A

1998-04-01

To determine the initial signaling event in the vascular permeability increase after high airway pressure injury, we compared groups of lungs ventilated at different peak inflation pressures (PIPs) with (gadolinium group) and without (control group) infusion of 20 microM gadolinium chloride, an inhibitor of endothelial stretch-activated cation channels. Microvascular permeability was assessed by using the capillary filtration coefficient (Kfc), a measure of capillary hydraulic conductivity. Kfc was measured after ventilation for 30-min periods with 7, 20, and 30 cmH2O PIP with 3 cmH2O positive end-expiratory pressure and with 35 cmH2O PIP with 8 cmH2O positive end-expiratory pressure. In control lungs, Kfc increased significantly to 1.8 and 3.7 times baseline after 30 and 35 cmH2O PIP, respectively. In the gadolinium group, Kfc was unchanged from baseline (0.060 +/- 0.010 ml . min-1 . cmH2O-1 . 100 g-1) after any PIP ventilation period. Pulmonary vascular resistance increased significantly from baseline in both groups before the last Kfc measurement but was not different between groups. These results suggest that microvascular permeability is actively modulated by a cellular response to mechanical injury and that stretch-activated cation channels may initiate this response through increases in intracellular calcium concentration.

In vivo evaluation of neutron capture therapy effectivity using calcium phosphate-based nanoparticles as Gd-DTPA delivery agent.

PubMed

Dewi, Novriana; Mi, Peng; Yanagie, Hironobu; Sakurai, Yuriko; Morishita, Yasuyuki; Yanagawa, Masashi; Nakagawa, Takayuki; Shinohara, Atsuko; Matsukawa, Takehisa; Yokoyama, Kazuhito; Cabral, Horacio; Suzuki, Minoru; Sakurai, Yoshinori; Tanaka, Hiroki; Ono, Koji; Nishiyama, Nobuhiro; Kataoka, Kazunori; Takahashi, Hiroyuki

2016-04-01

A more immediate impact for therapeutic approaches of current clinical research efforts is of major interest, which might be obtained by developing a noninvasive radiation dose-escalation strategy, and neutron capture therapy represents one such novel approach. Furthermore, some recent researches on neutron capture therapy have focused on using gadolinium as an alternative or complementary for currently used boron, taking into account several advantages that gadolinium offers. Therefore, in this study, we carried out feasibility evaluation for both single and multiple injections of gadolinium-based MRI contrast agent incorporated in calcium phosphate nanoparticles as neutron capture therapy agent. In vivo evaluation was performed on colon carcinoma Col-26 tumor-bearing mice irradiated at nuclear reactor facility of Kyoto University Research Reactor Institute with average neutron fluence of 1.8 × 10(12) n/cm(2). Antitumor effectivity was evaluated based on tumor growth suppression assessed until 27 days after neutron irradiation, followed by histopathological analysis on tumor slice. The experimental results showed that the tumor growth of irradiated mice injected beforehand with Gd-DTPA-incorporating calcium phosphate-based nanoparticles was suppressed up to four times higher compared to the non-treated group, supported by the results of histopathological analysis. The results of antitumor effectivity observed on tumor-bearing mice after neutron irradiation indicated possible effectivity of gadolinium-based neutron capture therapy treatment.

Assessment of the body burden of chelatable lead: a model and its application to lead workers.

PubMed Central

Araki, S; Ushio, K

1982-01-01

A hypothetical model was introduced to estimate the body burden of chelatable lead from the mobilisation yield of lead by calcium disodium ethylenediamine tetra-acetate (CaEDTA). It was estimated that, on average, 14 and 19% of the body burden was mobilised into the urine during the 24 hours after an injection of 53.4 mumol (20 mg) and 107 mumol (40 mg) CaEDTA per kg bodyweight, respectively. The body burden of chelatable lead ranged from 4 mumol (0.8 mg) to 120 mumol (24.9 mg) (mean 37 mumol (7.7 mg) in lead workers with blood lead concentrations of 0.3-2.9 mumol/kg (6-60 microgram/100 g) (mean 1.4 mumol/kg (29 microgram/100 g)). There were linear relationships between blood lead concentrations and body burden of chelatable lead on a log scale. PMID:6802167

Growth control in colon epithelial cells: gadolinium enhances calcium-mediated growth regulation.

PubMed

Attili, Durga; Jenkins, Brian; Aslam, Muhammad Nadeem; Dame, Michael K; Varani, James

2012-12-01

Gadolinium, a member of the lanthanoid family of transition metals, interacts with calcium-binding sites on proteins and other biological molecules. The overall goal of the present investigation was to determine if gadolinium could enhance calcium-induced epithelial cell growth inhibition in the colon. Gadolinium at concentrations as low as 1-5 μM combined with calcium inhibits proliferation of human colonic epithelial cells more effectively than calcium alone. Gadolinium had no detectable effect on calcium-induced differentiation in the same cells based on change in cell morphology, induction of E-cadherin synthesis, and translocation of E-cadherin from the cytosol to the cell surface. When the colon epithelial cells were treated with gadolinium and then exposed to increased calcium concentrations, movement of extracellular calcium into the cell was suppressed. In contrast, gadolinium treatment had no effect on ionomycin-induced release of stored intracellular calcium into the cytoplasm. Whether these in vitro observations can be translated into an approach for reducing abnormal proliferation in the colonic mucosa (including polyp formation) is not known. These results do, however, provide an explanation for our recent findings that a multi-mineral supplement containing all of the naturally occurring lanthanoid metals including gadolinium are more effective than calcium alone in preventing colon polyp formation in mice on a high-fat diet.

Gadolinium-enhanced magnetic resonance angiography in renal artery stenosis: comparison with digital subtraction angiography.

PubMed

Law, Y M; Tay, K H; Gan, Y U; Cheah, F K; Tan, B S

2008-04-01

To evaluate the accuracy of gadolinium-enhanced magnetic resonance angiography in assessing renal artery stenosis compared to catheter digital subtraction angiography. Retrospective study. Singapore General Hospital. Records of patients who underwent magnetic resonance angiography as well as digital subtraction angiography for assessment of renal artery stenosis from January 2003 to December 2005 were reviewed. There were 27 patients (14 male, 13 female) with a mean age of 62 (range, 44-77) years. There were 10 patients with renal transplants; their native renal arteries were not evaluated. Each of the two experienced interventional and body magnetic resonance radiologists, who were blinded to the results, reviewed the digital subtraction angiography and magnetic resonance angiography images respectively. Digital subtraction angiography was used as the standard of reference. A total of 39 renal arteries from these 27 patients were evaluated. One of the arteries was previously stented and could not be assessed with magnetic resonance angiography due to severe artefacts. Of the remaining 38 renal arteries, two were graded as normal, seven as having mild stenosis (<50%), eight as having moderate stenosis (> or =50% but <75%), and 21 as having severe stenosis (> or =75%). Magnetic resonance angiography and digital subtraction angiography were concordant in 89% of the arteries; magnetic resonance angiography overestimated the degree of stenosis in 8% and underestimated it in 3% of them. In the evaluation of clinically significant renal artery stenosis (> or =50%) with magnetic resonance angiography, the overall sensitivity, specificity, positive predictive value, and negative predictive value were 97%, 67%, 90%, and 86% respectively. The sensitivity and specificity of magnetic resonance angiography in transplant renal artery stenosis was 100%. CONCLUSION. Our experience suggested that gadolinium-enhanced magnetic resonance angiography is a sensitive non-invasive modality useful in the assessment of clinically significant renal artery stenosis.

The apparent inversion time for optimal delayed enhancement magnetic resonance imaging differs between the right and left ventricles.

PubMed

Desai, Milind Y; Gupta, Sandeep; Bomma, Chandra; Tandri, Harikrishna; Foo, Thomas K; Lima, Joao A C; Bluemke, David A

2005-01-01

Delayed post-contrast magnetic resonance (MR) imaging involves suppression of signal from myocardium using inversion times (TI) between 150-225 ms, when the myocardium appears dark and fibrotic scar appears bright. We noticed that at a TI optimized for signal suppression of the left ventricle (LV), the right ventricle (RV) appeared brighter. The purpose of this study was to evaluate the TI for signal suppression in RV compared to LV, and to try and identify the cause of this observation. Methods. We studied 31 patients (ages ranged from 17-79 years, 11 females) who had an MR scan on a 1.5 T GE scanner. Delayed post-contrast short-axis images were obtained 20 minutes after injection of 0.2 mmol/kg of intravenous gadolinium chelate. TI optimization was performed by acquiring a range of TI times within a single breath hold, in increments of 25 msec. The TI time that resulted in lowest signal for the RV arid LV was recorded. With the imaging sequence employed, the TI leading to LV signal suppression ranged from 150-225 ms. At the TI that resulted in LV signal suppression, the corrected signal from the RV was significantly higher as compared to the LV (29 +/- 13 au vs. 15 +/- 8 au, p < 0.001). The findings were similar using only the body coil. The TI required to suppress the RV was usually < or =150 msec. The observation persisted before and after gadolinium infusion. The TI for myocardial signal suppression appears to be different between LV and RV. Potential mechanisms include partial volume averaging with fat or blood pool (related to increased trabeculation) in the RV. Alternatively, increased blood pool signal (within Thebesian veins or arterioluminal communications) in RV compared to LV leads to altered TI times due to similar partial volume effects.

Ca(2+) regulates fluid shear-induced cytoskeletal reorganization and gene expression in osteoblasts

NASA Technical Reports Server (NTRS)

Chen, N. X.; Ryder, K. D.; Pavalko, F. M.; Turner, C. H.; Burr, D. B.; Qiu, J.; Duncan, R. L.

2000-01-01

Osteoblasts subjected to fluid shear increase the expression of the early response gene, c-fos, and the inducible isoform of cyclooxygenase, COX-2, two proteins linked to the anabolic response of bone to mechanical stimulation, in vivo. These increases in gene expression are dependent on shear-induced actin stress fiber formation. Here, we demonstrate that MC3T3-E1 osteoblast-like cells respond to shear with a rapid increase in intracellular Ca(2+) concentration ([Ca(2+)](i)) that we postulate is important to subsequent cellular responses to shear. To test this hypothesis, MC3T3-E1 cells were grown on glass slides coated with fibronectin and subjected to laminar fluid flow (12 dyn/cm(2)). Before application of shear, cells were treated with two Ca(2+) channel inhibitors or various blockers of intracellular Ca(2+) release for 0. 5-1 h. Although gadolinium, a mechanosensitive channel blocker, significantly reduced the [Ca(2+)](i) response, neither gadolinium nor nifedipine, an L-type channel Ca(2+) channel blocker, were able to block shear-induced stress fiber formation and increase in c-fos and COX-2 in MC3T3-E1 cells. However, 1, 2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-AM, an intracellular Ca(2+) chelator, or thapsigargin, which empties intracellular Ca(2+) stores, completely inhibited stress fiber formation and c-fos/COX-2 production in sheared osteoblasts. Neomycin or U-73122 inhibition of phospholipase C, which mediates D-myo-inositol 1,4,5-trisphosphate (IP(3))-induced intracellular Ca(2+) release, also completely suppressed actin reorganization and c-fos/COX-2 production. Pretreatment of MC3T3-E1 cells with U-73343, the inactive isoform of U-73122, did not inhibit these shear-induced responses. These results suggest that IP(3)-mediated intracellular Ca(2+) release is required for modulating flow-induced responses in MC3T3-E1 cells.

MRI with intrathecal MRI gadolinium contrast medium administration: a possible method to assess glymphatic function in human brain

PubMed Central

Ringstad, Geir

2015-01-01

Recently, the “glymphatic system” of the brain has been discovered in rodents, which is a paravascular, transparenchymal route for clearance of excess brain metabolites and distribution of compounds in the cerebrospinal fluid. It has already been demonstrated that intrathecally administered gadolinium (Gd) contrast medium distributes along this route in rats, but so far not in humans. A 27-year-old woman underwent magnetic resonance imaging (MRI) with intrathecal administration of gadobutrol, which distributed throughout her entire brain after 1 and 4.5 h. MRI with intrathecal Gd may become a tool to study glymphatic function in the human brain. PMID:26634147

Global and Regional Brain Assessment with Quantitative MR Imaging in Patients with Prior Exposure to Linear Gadolinium-based Contrast Agents.

PubMed

Kuno, Hirofumi; Jara, Hernán; Buch, Karen; Qureshi, Muhammad Mustafa; Chapman, Margaret N; Sakai, Osamu

2017-04-01

Purpose To assess the association of global and regional brain relaxation times in patients with prior exposure to linear gadolinium-based contrast agents (GBCAs). Materials and Methods The institutional review board approved this cross-sectional study. Thirty-five patients (nine who had received GBCA gadopentetate dimeglumine injections previously [one to eight times] and 26 patients who did not) who underwent brain magnetic resonance (MR) imaging with a mixed fast spin-echo pulse sequence were assessed. The whole brain was segmented according to white and gray matter by using a dual-clustering algorithm. In addition, regions of interest were measured in the globus pallidus, dentate nucleus, thalamus, and pons. The Mann-Whitney U test was used to assess the difference between groups. Multiple regression analysis was performed to assess the association of T1 and T2 with prior GBCA exposure. Results T1 values of gray matter were significantly shorter for patients with than for patients without prior GBCA exposure (P = .022). T1 of the gray matter of the whole brain (P < .001), globus pallidus (P = .002), dentate nucleus (P = .046), and thalamus (P = .026) and T2 of the whole brain (P = .004), dentate nucleus (P = .023), and thalamus (P = .002) showed a significant correlation with the accumulated dose of previous GBCA administration. There was no significant correlation between T1 and the accumulated dose of previous GBCA injections in the white matter (P = .187). Conclusion Global and regional quantitative assessments of T1 and T2 demonstrated an association with prior GBCA exposure, especially for gray matter structures. The results of this study confirm previous research findings that there is gadolinium deposition in wider distribution throughout the brain. © RSNA, 2016 Online supplemental material is available for this article.

Comparison of macrocyclic and acyclic chelators for gallium-68 radiolabelling.

PubMed

Tsionou, Maria Iris; Knapp, Caroline E; Foley, Calum A; Munteanu, Catherine R; Cakebread, Andrew; Imberti, Cinzia; Eykyn, Thomas R; Young, Jennifer D; Paterson, Brett M; Blower, Philip J; Ma, Michelle T

2017-10-24

Gallium-68 ( 68 Ga) is a positron-emitting isotope used for clinical PET imaging of peptide receptor expression. 68 Ga radiopharmaceuticals used in molecular PET imaging consist of disease-targeting biomolecules tethered to chelators that complex 68 Ga 3+ . Ideally, the chelator will rapidly, quantitatively and stably coordinate 68 Ga 3+ at room temperature, near neutral pH and low chelator concentration, allowing for simple routine radiopharmaceutical formulation. Identification of chelators that fulfil these requirements will facilitate development of kit-based 68 Ga radiopharmaceuticals. Herein the reaction of a range of widely used macrocyclic and acyclic chelators with 68 Ga 3+ is reported. Radiochemical yields have been measured under conditions of varying chelator concentrations, pH (3.5 and 6.5) and temperature (25 and 90 °C). These chelators are: 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA), 1,4,7-triazacyclononane macrocycles substituted with phosphonic (NOTP) and phosphinic (TRAP) groups at the amine, bis(2-hydroxybenzyl)ethylenediaminediacetic acid (HBED), a tris(hydroxypyridinone) containing three 1,6-dimethyl-3-hydroxypyridin-4-one groups (THP) and the hexadentate tris(hydroxamate) siderophore desferrioxamine-B (DFO). Competition studies have also been undertaken to assess relative complexation efficiencies of each chelator for 68 Ga 3+ under different pH and temperature conditions. Performing radiolabelling reactions at pH 6.5, 25 °C and 5-50 μM chelator concentration resulted in near quantitative radiochemical yields for all chelators, except DOTA. Radiochemical yields either decreased or were not substantially improved when the reactions were undertaken at lower pH or at higher temperature, except in the case of DOTA. THP and DFO were the most effective 68 Ga 3+ chelators at near-neutral pH and 25 °C, rapidly providing near-quantitative radiochemical yields at very low chelator concentrations. NOTP and HBED were only slightly less effective under these conditions. In competition studies with all other chelators, THP demonstrated highest reactivity for 68 Ga 3+ complexation under all conditions. These data point to THP possessing ideal properties for rapid, one-step kit-based syntheses of 68 Ga-biomolecules for molecular PET imaging. LC-MS and 1 H, 13 C{ 1 H} and 71 Ga NMR studies of HBED complexes of Ga 3+ showed that under the analytical conditions employed in this study, multiple HBED-bound Ga complexes exist. X-ray diffraction data indicated that crystals isolated from these solutions contained octahedral [Ga(HBED)(H 2 O)], with HBED coordinated in a pentadentate N 2 O 3 mode, with only one phenolic group coordinated to Ga 3+ , and the remaining coordination site occupied by a water molecule.

Growth Control in Colon Epithelial Cells: Gadolinium Enhances Calcium-Mediated Growth Regulation

PubMed Central

Attili, Durga; Jenkins, Brian; Aslam, Muhammad Nadeem; Dame, Michael K.

2013-01-01

Gadolinium, a member of the lanthanoid family of transition metals, interacts with calcium-binding sites on proteins and other biological molecules. The overall goal of the present investigation was to determine if gadolinium could enhance calcium-induced epithelial cell growth inhibition in the colon. Gadolinium at concentrations as low as 1–5 µM combined with calcium inhibits proliferation of human colonic epithelial cells more effectively than calcium alone. Gadolinium had no detectable effect on calcium-induced differentiation in the same cells based on change in cell morphology, induction of E-cadherin synthesis, and translocation of E-cadherin from the cytosol to the cell surface. When the colon epithelial cells were treated with gadolinium and then exposed to increased calcium concentrations, movement of extracellular calcium into the cell was suppressed. In contrast, gadolinium treatment had no effect on ionomycin-induced release of stored intracellular calcium into the cytoplasm. Whether these in vitro observations can be translated into an approach for reducing abnormal proliferation in the colonic mucosa (including polyp formation) is not known. These results do, however, provide an explanation for our recent findings that a multi-mineral supplement containing all of the naturally occurring lanthanoid metals including gadolinium are more effective than calcium alone in preventing colon polyp formation in mice on a high-fat diet. PMID:23008064

Promising Bifunctional Chelators for Copper 64-PET imaging: Practical 64Cu Radiolabeling and High In Vitro and In Vivo Complex Stability

PubMed Central

Wu, Ningjie; Kang, Chi Soo; Sin, Inseok; Ren, Siyuan; Liu, Dijie; Ruthengael, Varyanna C.; Lewis, Michael R.; Chong, Hyun-Soon

2016-01-01

Positron emission tomography (PET) using copper-64 is a sensitive and non-invasive imaging technique for diagnosis and staging of cancer. A bifunctional chelator that can present rapid radiolabeling kinetics and high complex stability with 64Cu is a critical component for targeted PET imaging. Bifunctional chelates 3p-C-NE3TA, 3p-C-NOTA, and 3p-C-DE4TA were evaluated for complexation kinetics and stability with 64Cu in vitro and in vivo. Hexadentate 3p-C-NOTA and heptadentate 3p-C-NE3TA possess a smaller TACN-based macrocyclic backbone, while nonadentate 3p-C-DE4TA is constructed on a larger CYCLEN-based ring. The frequently explored chelates of 64Cu, octadentate C-DOTA and hexadentate C-NOTA were also comparatively evaluated. Radiolabeling kinetics of bifunctional chelators with 64Cu was assessed under mild conditions. All bifunctional chelates instantly bound to 64Cu in excellent radiolabeling efficiency at room temperature. C-DOTA was less efficient in binding 64Cu than all other chelates. All 64Cu-radiolabeled bifunctional chelates remained stable in human serum without any loss of 64Cu for 2 days. When challenged by an excess amount of EDTA, 64Cu complexes of 3p-C-NE3TA and 3p-C-NOTA were shown to be more stable than 64Cu-C-DOTA and 64Cu-C-DE4TA. 3p-C-NE3TA and 3p-C-NOTA displayed comparable in vitro and in vivo complex stability to 64Cu-C-NOTA. In vivo biodistribution result indicates that the 64Cu-radiolabeled complexes of 3p-C-NOTA and 3p-C-NE3TA possess excellent in vivo complex stability, while 64Cu-3p-C-DE4TA was dissociated as evidenced by high renal and liver retention in mice. The results of in vitro and in vivo studies suggest that the bifunctional chelates 3p-C-NOTA and 3p-C-NE3TA offer excellent chelation chemistry with 64Cu for potential PET imaging applications. PMID:26666778

A first principles kinetic Monte Carlo investigation of the adsorption and mobility of gadolinium on the (100) surface of tungsten

NASA Astrophysics Data System (ADS)

Samin, Adib J.; Zhang, Jinsuo

2017-05-01

An accurate characterization of lanthanide adsorption and mobility on tungsten surfaces is important for pyroprocessing. In the present study, the adsorption and diffusion of gadolinium on the (100) surface of tungsten was investigated. It was found that the hollow sites were the most energetically favorable for the adsorption. It was further observed that a magnetic moment was induced following the adsorption of gadolinium on the tungsten surface and that the system with adsorbed hollow sites had the largest magnetization. A pathway for the surface diffusion of gadolinium was determined to occur by hopping between the nearest neighbor hollow sites via the bridge site and the activation energy for the hop was calculated to be 0.75 eV. The surface diffusion process was further assessed using two distinct kinetic Monte Carlo models; one that accounted for lateral adsorbate interactions up to the second nearest neighbor and one that did not account for such interatomic interactions in the adlayer. When the lateral interactions were included in the simulations, the diffusivity was observed to have a strong dependence on coverage (for the coverage values being studied). The effects of lateral interactions were further observed in a one-dimensional simulation of the diffusion equation where the asymmetry in the surface coverage profile upon its approach to a steady state distribution was clear in comparison with the simulations which did not account for those interactions.

Quantitative assessment of the rheumatoid synovial microvascular bed by gadolinium-DTPA enhanced magnetic resonance imaging

PubMed Central

Gaffney, K.; Cookson, J.; Blades, S.; Coumbe, A.; Blake, D.

1998-01-01

OBJECTIVE—To examine the relation between rate of synovial membrane enhancement, intra-articular pressure (IAP), and histologically determined synovial vascularity in rheumatoid arthritis, using gadolinium-DTPA enhanced magnetic resonance imaging (MRI).
METHODS—Dynamic gadolinium-DTPA enhanced MRI was performed in 31 patients with knee synovitis (10 patients IAP study, 21 patients vascular morphometry study). Rate of synovial membrane enhancement was quantified by line profile analysis using the image processing package ANALYZE. IAP was measured using an intra-compartmental pressure monitor system. Multiple synovial biopsy specimens were obtained by a blind biopsy technique. Blood vessels were identified immunohistochemically using the endothelial cell marker QBend30 and quantified (blood vessel numerical density and fractional area).
RESULTS—Median blood vessel numerical density and fractional area were 77.5/mm2 (IQR; 69.3-110.7) and 5.6% (IQR; 3.4-8.5) respectively. The rate of synovial membrane enhancement (median 2.74 signal intensity units/s, IQR 2.0-3.8) correlated with both blood vessel numerical density (r = 0.46, p < 0.05) and blood vessel fractional area (r = 0.55, p < 0.02). IAP did not influence the rate of enhancement.
CONCLUSIONS—Gadolinium-DTPA enhanced MRI may prove to be a valuable technique for evaluating drugs that influence angiogenesis.

 Keywords: magnetic resonance imaging; rheumatoid arthritis; synovitis; vascularity PMID:9640130

Safety and Efficacy of Combined Chelation Therapy with Deferasirox and Deferoxamine in a Gerbil Model of Iron Overload

PubMed Central

Otto-Duessel, Maya; Brewer, Casey; Gonzalez, Ignacio; Nick, Hanspeter; Wood, John C.

2010-01-01

Introduction Combined therapy with deferoxamine (DFO) and deferasirox (DFX) may be performed empirically when DFX monotherapy fails. Given the lack of published data on this therapy, the study goal was to assess the safety and efficacy of combined DFO/DFX therapy in a gerbil model. Methods Thirty-two female Mongolian gerbils 8–10 weeks old were divided into 4 groups (sham chelated, DFO, DFX, DFO/DFX). Each received 10 weekly injections of 200 mg/kg iron dextran prior to initiation of 12 weeks of chelation. Experimental endpoints were heart and liver weights, iron concentration and histology. Results In the heart, there was no significant difference among the treatment groups for wet-to-dry ratio, iron concentration and iron content. DFX-treated animals exhibited lower organ weights relative to sham-chelated animals (less iron-mediated hypertrophy). DFO-treated organs did not differ from sham-chelated organs in any aspects. DFX significantly cleared hepatic iron. No additive effects were observed in the organs of DFO/DFX-treated animals. Conclusions Combined DFO/DFX therapy produced no detectable additive effect above DFX monotherapy in either the liver or heart, suggesting competition with spontaneous iron elimination mechanisms for chelatable iron. Combined therapy was well tolerated, but its efficacy could not be proven due to limitations in the animal model. PMID:19018129

Effects of tillage on the Fe oxides activation in soil

NASA Astrophysics Data System (ADS)

Chi, Guangyu; Chen, Xin; Shi, Yi; Wang, Jun; Zheng, Taihui

2009-07-01

Since mid-1950s, the wetland ecosystems in Sanjiang Plain of Northeast China have been experiencing greater changes in land use, which had negative effects on the soil environments. This study assessed the effects of soil tillage on the activation of soil Fe in the region. The test ecosystems included natural wetland, paddy field and upland field converted from wetland. Soil samples at the depths of 0-10 cm, 10-20 cm, 20-30 cm, 30-40 cm, 40-60 cm, 60-90 cm and 90-120 cm were collected from each of the ecosystems for the analysis of vertical distribution of soil pH, organic carbon, chelate Fe oxides and Fe(II). The results showed that the conversion of wetland into paddy field and upland field induced a decrease of organic carbon content in 0-10 cm soil layer by 61.8% (P <0.05) and 70.0% (P < 0.05), respectively. The correlations among iron forms and soil organic carbon showed that chelate Fe oxides and Fe(II) was correlated positively with soil organic carbon and chelate ratio had a more positive relationship with organic carbon than chelate Fe oxides and Fe(II). The results of chelate Fe oxides, Fe(II) and chelate ratio of Fe suggested that reclamation could prevent the Fe activation and organic matter is credited for having an important influence on the process of Fe activation.

Iron overload in thalassemia and related conditions: therapeutic goals and assessment of response to chelation therapies.

PubMed

Porter, John B; Shah, Farrukh T

2010-12-01

Transfusional iron loading inevitably results in hepatic iron accumulation, with variable extrahepatic distribution that is typically less pronounced in sickle cell disease than in thalassemia disorders. Iron chelation therapy has the goal of preventing iron-mediated tissue damage through controlling tissue iron levels, without incurring chelator-mediated toxicity. Historically, target levels for tissue iron control have been limited by the increased frequency of deferoxamine-mediated toxicity and low levels of iron loading. With newer chelation regimes, these limitations are less evident. The reporting of responses to chelation therapies has typically focused on average changes in serum ferritin in patient populations. This approach has three limitations. First, changes in serum ferritin may not reflect trends in iron balance equally in all patients or for all chelation regimens. Second, this provides no information about the proportion of patients likely respond. Third, this gives insufficient information about iron trends in tissues such as the heart. Monitoring of iron overload has advanced with the increasing use of MRI techniques to estimate iron balance (changes in liver iron concentration) and extrahepatic iron distribution (myocardial T2*). The term nonresponder has been increasingly used to describe individuals who fail to show a downward trend in one or more of these variables. Lack of a response of an individual may result from inadequate dosing, high transfusion requirement, poor treatment adherence, or unfavorable pharmacology of the chelation regime. This article scrutinizes evidence for response rates to deferoxamine, deferiprone (and combinations), and deferasirox. Copyright © 2010 Elsevier Inc. All rights reserved.

Rational Design, Development, and Stability Assessment of a Macrocyclic Four-Hydroxamate-Bearing Bifunctional Chelating Agent for 89 Zr.

PubMed

Seibold, Uwe; Wängler, Björn; Wängler, Carmen

2017-09-21

Zirconium-89 is a positron-emitting radionuclide of high interest for medical imaging applications with positron emission tomography (PET). For the introduction of this radiometal into biologically active targeting vectors, the chelating agent desferrioxamine B (DFO) is commonly applied. However, DFO is known to form 89 Zr complexes of limited in vivo stability. Herein we describe the rational design and chemical development of a new macrocyclic four-hydroxamate-bearing chelating agent-1,10,19,28-tetrahydroxy-1,5,10,14,19,23,28,32-octaazacyclohexatriacontan-2,6,11,15,20,24,29,33-octaone (CTH36)-for the stable complexation of Zr 4+ . For this purpose, we first performed computational studies to determine the optimal chelator geometry before we developed different synthesis pathways toward the target structures. The best results were obtained using an efficient solution-phase-based synthesis strategy toward the target chelating agent. To enable efficient and chemoselective conjugation to biomolecules, a tetrazine-modified variant of CTH36 was also developed. The excellent conjugation characteristics of the so-functionalized chelator were demonstrated on the example of the model peptide TCO-c(RGDfK). We determined the optimal 89 Zr radiolabeling parameters for CTH36 as well as its bioconjugate, and found that 89 Zr radiolabeling proceeds efficiently under very mild reaction conditions. Finally, we performed comparative complex stability tests for 89 Zr-CHT36-c(RGDfK) and 89 Zr-DFO-c(RGDfK), showing improved complex stability for the newly developed chelator CTH36. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Coronary wave energy: a novel predictor of functional recovery after myocardial infarction.

PubMed

De Silva, Kalpa; Foster, Paul; Guilcher, Antoine; Bandara, Asela; Jogiya, Roy; Lockie, Tim; Chowiencyzk, Phil; Nagel, Eike; Marber, Michael; Redwood, Simon; Plein, Sven; Perera, Divaka

2013-04-01

Revascularization after acute coronary syndromes provides prognostic benefit, provided that the subtended myocardium is viable. The microcirculation and contractility of the subtended myocardium affect propagation of coronary flow, which can be characterized by wave intensity analysis. The study objective was to determine in acute coronary syndromes whether early wave intensity analysis-derived microcirculatory (backward) expansion wave energy predicts late viability, defined by functional recovery. Thirty-one patients (58±11 years) were enrolled after non-ST elevation myocardial infarction. Regional left ventricular function and late-gadolinium enhancement were assessed by cardiac magnetic resonance imaging, before and 3 months after revascularization. The backward-traveling (microcirculatory) expansion wave was derived from wave intensity analysis of phasic coronary pressure and velocity in the infarct-related artery, whereas mean values were used to calculate hyperemic microvascular resistance. Twelve-hour troponin T, left ventricular ejection fraction, and percentage late-gadolinium enhancement mass were 1.35±1.21 µg/L, 56±11%, and 8.4±6.0%, respectively. The infarct-related artery backward-traveling (microcirculatory) expansion wave was inversely correlated with late-gadolinium enhancement infarct mass (r=-0.81; P<0.0001) and strongly predicted regional left ventricular recovery (r=0.68; P=0.001). By receiver operating characteristic analysis, a backward-traveling (microcirculatory) expansion wave threshold of 2.8 W m(-2) s(-2)×10(5) predicted functional recovery with sensitivity and specificity of 0.91 and 0.82 (AUC 0.88). Hyperemic microvascular resistance correlated with late-gadolinium enhancement mass (r=0.48; P=0.03) but not left ventricular recovery (r=-0.34; P=0.07). The microcirculation-derived backward expansion wave is a new index that correlates with the magnitude and location of infarction, which may allow for the prediction of functional myocardial recovery. Coronary wave intensity analysis may facilitate myocardial viability assessment during cardiac catheterization.

In vitro comparison of intracranial stent visibility using various concentrations of gadolinium contrast agent under 1.5 T and 3 T MR angiography.

PubMed

Chiang, Chen-Hua; Tseng, Ying-Chi; Chen, Ai-Chi; Huang, Yen-Lin; Chen, David Yen-Ting; Chen, Chi-Jen; Lin, Yen-Kuang; Hsu, Hui-Ling

2017-04-01

MR angiography (MRA) is an increasingly used evaluation method following intracranial stenting. However, the various artifacts created by the stent limit this technique. The purpose of this study was to investigate the effects of various concentrations of gadolinium contrast agent on the visibility and signal characteristics of two stents using the a contrast enhanced MRA technique. Two intracranial stents (Enterprise and Helistent) were placed in polyvinyl chloride tubes as vascular phantoms. They were filled with six different doses of gadolinium contrast agent (1.0, 2.0, 4.0, 6.0, 8.0, and 10.0 mmol/L dimeglumine gadopentetate, respectively) and imaged using 3 T and 1.5 T MR systems. Relative in-stent signal (RIS) was calculated and artificial luminal narrowing (ALN) was obtained using pixel by pixel analysis. The Enterprise stent, performed in both 1.5 T and 3 T MR systems, showed mean RIS values much less than those for the Helistent for all different doses of gadolinium solution. Increased gadolinium concentration resulted in a gradual reduction in RIS values in the Enterprise group. Also, ALN in the Enterprise group showed no or little change with various gadolinium doses. The Enterprise stent demonstrated good luminal visibility regardless of gadolinium concentration. The relative in-stent signals were more predictable in the Enterprise stent with various doses of gadolinium. Therefore, the Enterprise stent has been shown to provide better in-stent visibility compared with the Helistent using various gadolinium doses. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Gadolinium Use in Spine Pain Management Procedures for Patients with Contrast Allergies: Results in 527 Procedures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Safriel, Yair; Ang, Roberto; Ali, Muhammed

2008-03-15

Introduction. To review the safety and efficacy of gadolinium in spine pain management procedures in patients at high risk for a contrast reaction and who are not suitable candidates for the use of standard non-ionic contrast. Methods. We reviewed records over a 61-month period of all image-guided spinal pain management procedures where patients had allergies making them unsuitable candidates for standard non-ionic contrast and where gadolinium was used to confirm needle tip placement prior to injection of medication. Results. Three hundred and four outpatients underwent 527 procedures. A spinal needle was used in all but 41 procedures. Gadolinium was visualizedmore » using portable C-arm fluoroscopy in vivo allowing for confirmation of needle tip location. The gadolinium dose ranged from 0.2 to 10 ml per level. The highest dose received by one patient was 15.83 ml intradiscally during a three-level discogram. Three hundred and one patients were discharged without complication or known delayed complications. One patient had documented intrathecal injection but without sequelae and 2 patients who underwent cervical procedures experienced seizures requiring admission to the intensive care unit. Both the latter patients were discharged without any further complications. Conclusion. Based on our experience we recommend using gadolinium judiciously for needle tip confirmation. We feel more confident using gadolinium in the lumbar spine and in cervical nerve blocks. Gadolinium should probably not be used as an injectate volume expander. The indications for gadolinium use in cervical needle-guided spine procedures are less clear and use of a blunt-tipped needle should be considered.« less

Gd-labeled glycol chitosan as a pH-responsive magnetic resonance imaging agent for detecting acidic tumor microenvironments.

PubMed

Nwe, Kido; Huang, Ching-Hui; Tsourkas, Andrew

2013-10-24

Neoplastic lesions can create a hostile tumor microenvironment with low extracellular pH. It is commonly believed that these conditions can contribute to tumor progression as well as resistance to therapy. We report the development and characterization of a pH-responsive magnetic resonance imaging contrast agent for imaging the acidic tumor microenvironment. The preparation included the conjugation of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid 1-(2,5-dioxo-1-pyrrolidinyl) ester (DOTA-NHS) to the surface of a water-soluble glycol chitosan (GC) polymer, which contains pH-titrable primary amines, followed by gadolinium complexation (GC-NH2-GdDOTA). GC-NH2-GdDOTA had a chelate-to-polymer ratio of approximately1:24 and a molar relaxivity of 9.1 mM(-1) s(-1). GC-NH2-GdDOTA demonstrated pH-dependent cellular association in vitro compared to the control. It also generated a 2.4-fold enhancement in signal in tumor-bearing mice 2 h postinjection. These findings suggest that glycol chitosan coupled with contrast agents can provide important diagnostic information about the tumor microenvironment.

Identification and characterization of gadolinium(III) complexes in biological tissue extracts.

PubMed

Kahakachchi, Chethaka L; Moore, Dennis A

2010-07-01

The gadolinium species present in a rat kidney following intravenous administration of a gadolinium-based magnetic resonance contrast agent (Optimark™, Gadoversetamide injection) to a rat was examined in the present study. The major gadolinium species in the supernatant of the rat kidney tissue extracts was determined by reversed-phase liquid chromatography with online inductively coupled plasma optical emission spectrometry (HPLC-ICP-OES). The identity of the compound was established by liquid chromatography electrospray ionization mass spectrometry (LC-ESI-MS) detection. The principal gadolinium(III) complex in a rat kidney tissue extract was identified as Gd-DTPA-BMEA 24 Hrs and 7 days after a single intravenous injection of Optimark™ (gadoversetamide; Gd-DTPA-BMEA) at a dose of 5 mmol Gd/kg body weight. The study demonstrated for the first time the feasibility of the use of two complementary techniques, HPLC-ICP-OES and HPLC-ESI-MS to study the in vivo behavior of gadolinium-based magnetic resonance contrast media.

Assessment of the Efficacy of Chelate-Assisted Phytoextraction of Lead by Coffeeweed (Sesbania exaltata Raf.)

PubMed Central

Miller, Gloria; Begonia, Gregorio; Begonia, Maria; Ntoni, Jennifer; Hundley, Oscar

2008-01-01

Lead (Pb), depending upon the reactant surface, pH, redox potential and other factors can bind tightly to the soil with a retention time of many centuries. Soil-metal interactions by sorption, precipitation and complexation processes, and differences between plant species in metal uptake efficiency, transport, and susceptibility make a general prediction of soil metal bioavailability and risks of plant metal toxicity difficult. Moreover, the tight binding characteristic of Pb to soils and plant materials make a significant portion of Pb unavailable for uptake by plants. This experiment was conducted to determine whether the addition of ethylenediaminetetraacetic acid (EDTA), ethylene glycol tetraacetic acid (EGTA), or acetic acid (HAc) can enhance the phytoextraction of Pb by making the Pb soluble and more bioavailable for uptake by coffeeweed (Sesbania exaltata Raf.). Also we wanted to assess the efficacy of chelates in facilitating translocation of the metal into the above-ground biomass of this plant. To test the effect of chelates on Pb solubility, 2 g of Pb-spiked soil (1000 mg Pb/kg dry soil) were added to each 15 mL centrifuge tube. Chelates (EDTA, EGTA, HAc) in a 1:1 ratio with the metal, or distilled deionized water were then added. Samples were shaken on a platform shaker then centrifuged at the end of several time periods. Supernatants were filtered with a 0.45 μm filter and quantified by inductively coupled plasma-optical emission spectrometry (ICP-OES) to determine soluble Pb concentrations. Results revealed that EDTA was the most effective in bringing Pb into solution, and that maximum solubility was reached 6 days after chelate amendment. Additionally, a greenhouse experiment was conducted by planting Sesbania seeds in plastic tubes containing top soil and peat (2:1, v:v) spiked with various levels (0, 1000, 2000 mg Pb/kg dry soil) of lead nitrate. At six weeks after emergence, aqueous solutions of EDTA and/or HAc (in a 1:1 ratio with the metal) or distilled deionized water were applied to the root zones. Plants were harvested at 6 days after chelate addition to coincide with the duration of maximum metal solubility previously determined in this study. Results of the greenhouse experiment showed that coffeeweed was relatively tolerant to moderate levels of Pb and chelates as shown by very slight reductions in root and no discernable effects on shoot biomass. Root Pb concentrations increased with increasing levels of soil-applied Pb. Further increases in root Pb concentrations were attributed to chelate amendments. In the absence of chelates, translocation of Pb from roots to shoots was minimal. However, translocation dramatically increased in treatments with EDTA alone or in combination with HAc. Overall, the results of this study indicated that depending on the nature and type of Pb-contaminated soil being remediated, the bioavailability and uptake of Pb by coffeeweed can be enhanced by amending the soil with chelates especially after the plants have reached maximum biomass. PMID:19151439

Density of Gadolinium Nitrate Solutions for the High Flux Isotope Reactor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Taylor, Paul Allen; Lee, Denise L

2009-05-01

In late 1992, the High Flux Isotope Reactor (HFIR) was planning to switch the solution contained in the poison injection tank from cadmium nitrate to gadolinium nitrate. The poison injection system is an emergency system used to shut down the reactor by adding a neutron poison to the cooling water. This system must be able to supply a minimum of 69 pounds of gadolinium to the reactor coolant system in order to guarantee that the reactor would become subcritical. A graph of the density of gadolinium nitrate solutions over a concentration range of 5 to 30 wt% and a temperaturemore » range of 15 to 40{sup o}C was prepared. Routine density measurements of the solution in the poison injection tank are made by HFIR personnel, and an adaptation of the original graph is used to determine the gadolinium nitrate concentration. In late 2008, HFIR personnel decided that the heat tracing that was present on the piping for the poison injection system could be removed without any danger of freezing the solution; however, the gadolinium nitrate solution might get as cold as 5{sup o}C. This was outside the range of the current density-concentration correlation, so the range needed to be expanded. This report supplies a new density-concentration correlation that covers the extended temperature range. The correlation is given in new units, which greatly simplifies the calculation that is required to determine the pounds of gadolinium in the tank solution. The procedure for calculating the amount of gadolinium in the HFIR poison injection system is as follows: (1) Calculate the usable volume in the system; (2) Measure the density of the solution; (3) Calculate the gadolinium concentration using the following equation: Gd(lb/ft{sup 3}) = measured density (g/mL) x 34.681 - 34.785; (4) Calculate the amount of gadolinium in the system using the following equation: Amount of Gd(lb) = Gd concentration (lb/ft{sup 3}) x usable volume (ft{sup 3}). The equation in step 3 is exact for a temperature of 5{sup o}C, and overestimates the gadolinium concentration at all higher temperatures. This guarantees that the calculation is conservative, in that the actual concentration will be at least as high as that calculated. If an additional safety factor is desired, it is recommended that an administrative control limit be set that is higher than the required minimum amount of gadolinium.« less

Synergistic effect of chelators and Herbaspirillum sp. GW103 on lead phytoextraction and its induced oxidative stress in Zea mays.

PubMed

Govarthanan, Muthusamy; Kamala-Kannan, Seralathan; Kim, Seol Ah; Seo, Young-Seok; Park, Jung-Hee; Oh, Byung-Taek

2016-10-01

Phytoremediation is an in situ, low-cost strategy for cleanup of the sites contaminated with heavy metals. Experiments were conducted to assess the impact of synthetic chelators and plant growth-promoting rhizosphere bacteria (Herbaspirillum sp. GW103) on heavy metal lead (Pb) uptake in Z. mays cultivated in Pb-contaminated soil. The present study investigated the Pb phytoaccumulation rate and plant antioxidant enzyme activities in Z. mays exposed to 100 mg/kg of PbNO3. The combination of gluconic acid (GA) with Herbaspirillum sp. GW103 treatment showed higher Pb solubility (18.9 mg/kg) compared with other chelators. The chemical chelators showed the significant difference in phytoaccumulation as well as antioxidant enzyme activities. The antioxidant enzymes such as catalase, peroxidase and superoxide dismutase activities changed under Pb stress. The study indicated that increased activity of antioxidant enzymes may play as signal inducers to fight against Pb.

High specific heat superconducting composite

DOEpatents

Steyert, Jr., William A.

1979-01-01

A composite superconductor formed from a high specific heat ceramic such as gadolinium oxide or gadolinium-aluminum oxide and a conventional metal conductor such as copper or aluminum which are insolubly mixed together to provide adiabatic stability in a superconducting mode of operation. The addition of a few percent of insoluble gadolinium-aluminum oxide powder or gadolinium oxide powder to copper, increases the measured specific heat of the composite by one to two orders of magnitude below the 5.degree. K. level while maintaining the high thermal and electrical conductivity of the conventional metal conductor.

Gadolinium-based magnetic resonance imaging contrast agents in interventional radiology.

PubMed

Atar, Eli

2004-07-01

Gadolinium-based agents are widely used in magnetic resonance imaging as contrast agents. These agents are radio-opaque enough for diagnostic imaging of the vascular tree by using digitally subtracted images as well as for imaging of the biliary system and the urinary tract. The recommended doses for gadolinium do not impair renal function or cause adverse reactions in patients with iodine sensitivity; thus patients with such conditions can safely undergo diagnostic angiography, either by MRI angiography or by catheterization using gadolinium as contrast agent, for diagnostic and therapeutic purposes.

Rare-Earth Ion-Host Lattice Interactions: 15. Analysis of the Spectra of Nd3+ in Gd3Sc2Ga3O12.

DTIC Science & Technology

1984-05-01

Luminescence of Cr3+ Ions in Gadolinium Gallium and Gadolinium Scandium Gallium Garnet CT’stals, Soy. J. Quant. Electron. 12 (1982), 1124. 6M. Dutoit, J. C...Shcherbakov, Absolute Quantum Efficiency of the Luminescence of Cr3+ Ions in Gadolinium Gallium and Gadolinium Scandium Gallium Garnet Crystals, Soy. J...HDL Project: 324332 19. KEY WORDS (Continue on reverse side it necessary end Identify by block number) Rare earth Mixed garnet Spectra Laser Judd-Ofelt

Theoretical study of structure and stability of small gadolinium carboxylate complexes in liquid scintillator solvents.

PubMed

Huang, Pin-Wen

2014-09-01

The structural properties of three small gadolinium carboxylate complexes in three liquid scintillator solvents (pseudocumene, linear alkylbenzene, and phenyl xylylethane) were theoretically investigated using density functional theory (B3LYP/LC-RECP) and polarizable continuum model (PCM). The average interaction energy between gadolinium atom and carboxylate ligand (E(int)) and the energy difference of the highest singly occupied molecular orbital and lowest unoccupied molecular orbital (Δ(SL)) were calculated to evaluate and compare the relative stability of these complexes in solvents. The calculation results show that the larger (with a longer alkyl chain) gadolinium carboxylate complex has greater stability than the smaller one, while these gadolinium carboxylates in linear alkylbenzene were found to have greater stability than those in the other two solvents.

The Effect of Pressure and Temperature on Separation of Free Gadolinium(III) From Gd-DTPA Complex by Nanofiltration-Complexation Method

NASA Astrophysics Data System (ADS)

Rahayu, Iman; Anggraeni, Anni; Ukun, MSS; Bahti, Husein H.

2017-05-01

Nowdays, the utilization of rare earth elements has been carried out widely in industry and medicine, one of them is gadolinium in Gd-DTPA complex is used as a contrast agent in a magnetic resonance imaging (MRI) diagnostic to increase the visual contrast between normal tissue and diseased. Although the stability of a given complex may be high enough, the complexation step couldnot have been completed, so there is possible to gadolinium(III) in the complex compound. Therefore, the function of that compounds should be dangerous because of the toxicity of gadolinium(III) in human body. So, it is necessarry to separate free gadolinium(III) from Gd-DTPA complex by nanofiltration-complexation. The method of this study is complexing of Gd2O3 with DTPA ligand by reflux and separation of Gd-DTPA complex from gadolinium(III) with a nanofiltration membrane on the variation of pressures(2, 3, 4, 5, 6 bars) and temperature (25, 30, 35, 40 °C) and determined the flux and rejection. The results of this study are the higher of pressures and temperatures, permeation flux are increasing and ion rejections are decreasing and gave the free gadolinium(III) rejection until 86.26%.

Helium defectoscopy of cerium gadolinium ceramics Ce0.8Gd0.2O1.9 with a submicrocrystalline structure in the impurity disorder region

NASA Astrophysics Data System (ADS)

Koromyslov, A. V.; Zhiganov, A. N.; Kovalenko, M. A.; Kupryazhkin, A. Ya.

2013-12-01

The concentration of impurity anion vacancies formed upon the dissociation of gadolinium-vacancy complexes has been determined using helium defectoscopy of the cerium gadolinium ceramics Ce0.8Gd0.2O1.9 with a submicrocrystalline structure in the temperature range T = 740-1123 K and at saturation pressures ranging from 0.05 to 15 MPa. It has been found that the energy of dissociation of gadoliniumvacancy complexes is E {eff/ D }= 0.26 ± 0.06 eV, and the energy of dissolution of helium in anion vacancies in the impurity disorder region is E P = -0.31 ± 0.09 eV. The proposed mechanism of dissolution has been confirmed by the investigation of the electrical conductivity of the cerium gadolinium ceramics, as well as by the high-speed molecular dynamics simulation of the dissociation of gadolinium-vacancy complexes. It has been assumed that a decrease in the effective dissolution energy in comparison with the results of the previously performed low-temperature investigations is caused by the mutual repulsion of vacancies formed upon the dissociation of gadolinium-vacancy complexes in highly concentrated solutions of gadolinium in CeO2 with increasing temperature.

Synthesis and radiolabeling of chelator-RNA aptamer bioconjugates with copper-64 for targeted molecular imaging

PubMed Central

Rockey, William M.; Huang, Ling; Kloepping, Kyle C.; Baumhover, Nicholas J.; Giangrande, Paloma H.; Schultz, Michael K.

2014-01-01

Ribonucleic acid (RNA) aptamers with high affinity and specificity for cancer-specific cell-surface antigens are promising reagents for targeted molecular imaging of cancer using positron emission tomography (PET). For this application, aptamers must be conjugated to chelators capable of coordinating PET-radionuclides (e.g. copper-64, 64Cu) to enable radiolabeling for in vivo imaging of tumors. This study investigates the choice of chelator and radiolabeling parameters such as pH and temperature for the development of 64Cu-labeled RNA-based targeted agents for PET imaging. The characterization and optimization of labeling conditions are described for four chelator-aptamer complexes. Three commercially available bifunctional macrocyclic chelators (1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid mono N-hydroxysuccinimide [DOTA-NHS]; S-2-(4-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid [p-SCN-Bn-NOTA]; and p-SCN-Bn-3,6,9,15-tetraazabicyclo [9.3.1]pentadeca-1(15),11,13-triene-3,6,9-triacetic acid [p-SCN-Bn-PCTA]), as well as the polyamino-macrocyclic diAmSar (3,6,10,13,16,19-hexaazabicyclo[6.6.6] icosane-1,8-diamine) were conjugated to A10–3.2, a RNA aptamer which has been shown to bind specifically to a prostate cancer-specific cell-surface antigen (PSMA). Although a commercial bifunctional version of diAmSar was not available, RNA conjugation with this chelator was achieved in a two-step reaction by the addition of a disuccinimidyl suberate linker. Radiolabeling parameters (e.g. pH, temperature, and time) for each chelator-RNA conjugate were assessed in order to optimize specific activity and RNA stability. Furthermore, the radiolabeled chelator-coupled RNA aptamers were evaluated for binding specificity to their target antigen. In summary, key parameters were established for optimal radiolabeling of RNA aptamers for eventual PET imaging with 64Cu. PMID:21658962

Differential targeting of the cyclin-dependent kinase inhibitor, p21CIP1/WAF1, by chelators with anti-proliferative activity in a range of tumor cell-types

PubMed Central

Moussa, Rayan S.; Kovacevic, Zaklina; Richardson, Des R.

2015-01-01

Chelators such as 2-hydroxy-1-napthylaldehyde isonicotinoyl hydrazone (311) and di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT) target tumor cell iron pools and inhibit proliferation. These agents also modulate multiple targets, one of which is the cyclin-dependent kinase inhibitor, p21. Hence, this investigation examined the mechanism of action of these compounds in targeting p21. All the chelators up-regulated p21 mRNA in the five tumor cell-types assessed. In contrast, examining their effect on total p21 protein levels, these agents induced either: (1) down-regulation in MCF-7 cells; (2) up-regulation in SK-MEL-28 and CFPAC-1 cells; or (3) had no effect in LNCaP and SK-N-MC cells. The nuclear localization of p21 was also differentially affected by the ligands depending upon the cell-type, with it being decreased in MCF-7 cells, but increased in SK-MEL-28 and CFPAC-1 cells. Further studies assessing the mechanisms responsible for these effects demonstrated that p21 expression was not correlated with p53 status, suggesting a p53-independent mechanism. Considering this, we examined proteins that modulate p21 independently of p53, namely NDRG1, MDM2 and ΔNp63. These studies demonstrated that a dominant negative MDM2 isoform (p75MDM2) closely resembled p21 expression in response to chelation in three cell lines. These data suggest MDM2 may be involved in the regulation of p21 by chelators. PMID:26335183

Why the NIH Trial to Assess Chelation Therapy (TACT) Should Be Abandoned

PubMed Central

Atwood, Kimball C.; Woeckner, Elizabeth; Baratz, Robert S.; Sampson, Wallace I.

2008-01-01

The National Institutes of Health (NIH) Trial to Assess Chelation Therapy (TACT) was begun in 2003 and is expected to be completed in 2009. It is a trial of office-based, intravenous disodium ethylene-diamine-tetra-acetic acid (Na2EDTA) as a treatment for coronary artery disease (CAD). A few case series in the 1950s and early 1960s had found Na2EDTA to be ineffective for CAD or peripheral vascular disease (PVD). Nevertheless, a few hundred physicians, almost all of whom advocate other dubious treatments, continued to peddle chelation as an office treatment. They claim that chelation dramatically improves symptoms and prolongs life in 80% to 90% of patients. In response, academics performed 4 controlled trials during the 1990s. None favored chelation, but chelationists repudiated those findings. We have investigated the method and the trial. We present our findings in 4 parts: history, origin and nature of the TACT, state of the evidence, and risks. We present evidence that chelationists and their organization, the American College for Advancement in Medicine, used political connections to pressure the NIH to fund the TACT. The TACT protocols justified the trial by misrepresenting case series and by ignoring evidence of risks. The trial employs nearly 100 unfit co-investigators. It conflates disodium EDTA and another, somewhat safer drug. It lacks precautions necessary to minimize risks. The consent form reflects those shortcomings and fails to disclose apparent proprietary interests. The trial's outcome will be unreliable and almost certainly equivocal, thus defeating its stated purpose. We conclude that the TACT is unethical, dangerous, pointless, and wasteful. It should be abandoned. PMID:18596934

Experimental lead intoxication in dogs: a comparison of blood lead and urinary delta-aminolevulinic acid following intoxication and chelation therapy.

PubMed Central

Green, R A; Selby, L A; Zumwalt, R W

1978-01-01

Intravenous lead administration to dogs produced an acute syndrome of lead intoxication charcterized by depression, vomiting, anorexia and weight loss. The effect of chelation therapy with calcium disodium ethylene diamine tetraacetate, penicillamine or both was determined by serially monitoring changes in blood lead and urine delta-aminolevulinic acid. Following therapy, blood lead values were significantly lower in chelated dogs than non-treated lead exposed dogs on days 7 and 10. Urine delta-aminolevulinic acid at day 7 was significantly higher in untreated lead exposed dogs than in other groups. There was no significant difference in blood lead or urine delta-aminolevulinic acid between lead intoxicated dogs which underwent the indicated chelation therapy protocols. There was, however, a trend for higher urinary delta-aminolevulinic acid excretion in those intoxicated dogs undergoing calcium disodium ethylene diamine tetraacetate therapy as opposed to those undergoing penicilamine therapy. There was no significant correlation between blood lead and urinary delta-aminolevulinic acid previous to lead exposure. However, after lead exposure significant correlation was present at days 4, 7, 10 and 14. Certain lead exposed dogs following chelation therapy were noted to have normal blood lead levels but elevated urinary delta-aminolevulinic acid suggesting that blood lead does not always correlate with metabolic effects of lead in the body. Urinary delta-aminolevulinic acid was therefore recommended as an additional laboratory parameter which improved assessment of lead exposure in dogs, particularly in determining adequacy of chelation therapy. PMID:667707

Lanthanide ion (III) complexes of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraaminophosphonate (DOTA-4AmP8−) for dual biosensing of pH with CEST (chemical exchange saturation transfer) and BIRDS (biosensor imaging of redundant deviation in shifts)

PubMed Central

Huang, Yuegao; Coman, Daniel; Ali, Meser M.; Hyder, Fahmeed

2014-01-01

Relaxivity based magnetic resonance of phosphonated ligands chelated with gadolinium (Gd3+) shows promise for pH imaging. However instead of monitoring the paramagnetic effect of lanthanide complexes on the relaxivity of water protons, biosensor (or molecular) imaging with magnetic resonance is also possible by detecting either the non-exchangeable or the exchangeable protons on the lanthanide complexes themselves. The non-exchangeable protons (e.g., –CHx, where 3≥x≥1) are detected using a three-dimensional chemical shift imaging method called Biosensor Imaging of Redundant Deviation in Shifts (BIRDS), whereas the exchangeable protons (e.g., –OH or –NHy, where 2≥y≥1) are measured with Chemical Exchange Saturation Transfer (CEST) contrast. Here we tested the feasibility of BIRDS and CEST for pH imaging of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraaminophosphonate (DOTA-4AmP8−) chelated with thulium (Tm3+) and ytterbium (Yb3+). BIRDS and CEST experiments show that both complexes are responsive to pH and temperature changes. Higher pH and temperature sensitivities are obtained with BIRDS for either complex when using the chemical shift difference between two proton resonances vs. using the chemical shift of a single proton resonance, thereby eliminating the need to use water resonance as reference. While CEST contrast for both agents is linearly dependent on pH within a relatively large range (i.e., 6.3-7.9), much stronger CEST contrast is obtained with YbDOTA-4AmP5− than with TmDOTA-4AmP5−. In addition, we demonstrate the prospect of using BIRDS to calibrate CEST as new platform for quantitative pH imaging. PMID:24801742

Lanthanide ion (III) complexes of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraaminophosphonate for dual biosensing of pH with chemical exchange saturation transfer (CEST) and biosensor imaging of redundant deviation in shifts (BIRDS).

PubMed

Huang, Yuegao; Coman, Daniel; Ali, Meser M; Hyder, Fahmeed

2015-01-01

Relaxivity-based magnetic resonance of phosphonated ligands chelated with gadolinium (Gd(3+)) shows promise for pH imaging. However instead of monitoring the paramagnetic effect of lanthanide complexes on the relaxivity of water protons, biosensor (or molecular) imaging with magnetic resonance is also possible by detecting either the nonexchangeable or the exchangeable protons on the lanthanide complexes themselves. The nonexchangeable protons (e.g. -CHx, where 3 ≥ x ≥ 1) are detected using a three-dimensional chemical shift imaging method called biosensor imaging of redundant deviation in shifts (BIRDS), whereas the exchangeable protons (e.g. -OH or -NHy , where 2 ≥ y ≥ 1) are measured with chemical exchange saturation transfer (CEST) contrast. Here we tested the feasibility of BIRDS and CEST for pH imaging of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraaminophosphonate (DOTA-4AmP(8-)) chelated with thulium (Tm(3+) ) and ytterbium (Yb(3+)). BIRDS and CEST experiments show that both complexes are responsive to pH and temperature changes. Higher pH and temperature sensitivities are obtained with BIRDS for either complex when using the chemical shift difference between two proton resonances vs using the chemical shift of a single proton resonance, thereby eliminating the need to use water resonance as reference. While CEST contrast for both agents is linearly dependent on pH within a relatively large range (i.e. 6.3-7.9), much stronger CEST contrast is obtained with YbDOTA-4AmP(5-) than with TmDOTA-4AmP(5-). In addition, we demonstrate the prospect of using BIRDS to calibrate CEST as new platform for quantitative pH imaging. Copyright © 2014 John Wiley & Sons, Ltd.

The Effect of gadolinium on the ESR response of alanine and ammonium tartrate exposed to thermal neutrons.

PubMed

Marrale, Maurizio; Brai, Maria; Gennaro, Gaetano; Bartolotta, Antonio; D'Oca, Maria Cristina

2008-02-01

Many efforts have been made to develop neutron capture therapy (NCT) for cancer treatment. Among the challenges in using NCT is the characterization of the features of the mixed radiation field and of its components. In this study, we examined the enhancement of the ESR response of pellets of alanine and ammonium tartrate with gadolinium oxide exposed to a thermal neutron beam. In particular, the ESR response of these dosimeters as a function of the gadolinium content inside the dosimeter was analyzed. We found that the addition of gadolinium improves the sensitivity of both alanine and ammonium tartrate. However, the use of gadolinium reduces or abolishes tissue equivalence because of its high atomic number (Z(Gd) = 64). Therefore, it is necessary to find the optimum compromise between the sensitivity to thermal neutrons and the reduction of tissue equivalence. Our analysis showed that a low concentration of gadolinium oxide (of the order of 5% of the total mass of the dosimeter) can enhance the thermal neutron sensitivity more than 13 times with an insignificant reduction of tissue equivalence.

Iron-Chelating Therapy for Transfusional Iron Overload

PubMed Central

Brittenham, Gary M.

2011-01-01

A 16-year-old boy with sickle cell anemia undergoes routine screening with transcranial Doppler ultrasonography to assess the risk of stroke. This examination shows an abnormally elevated blood-flow velocity in the middle cerebral artery. The hemoglobin level is 7.2 g per deciliter, the reticulocyte count is 12.5%, and the fetal hemoglobin level is 8.0%. Long-term treatment with red-cell transfusion is initiated to prevent stroke. A hematologist recommends prophylactic iron-chelating therapy. PMID:21226580

Clinical application of a gadolinium-based capsule as an MRI contrast agent in slow transit constipation diagnostics.

PubMed

Zhi, M; Zhou, Z; Chen, H; Xiong, F; Huang, J; He, H; Zhang, M; Su, M; Gao, X; Hu, P

2017-06-01

As a traditional method for the assessment of colon dynamics, radio-opaque markers (ROMs) are limited in clinical use because of their ionizing radiation. We compared the accuracy and applicability of gadolinium-based capsules with ROMs in the measurement of colon dynamics in healthy controls and slow transit constipation (STC) patients. Seven patients with STC and nine healthy controls under a normal diet orally consumed ROMs and gadolinium-based capsules simultaneously. All subjects underwent X-ray and magnetic resonance imaging (MRI). Healthy control images were acquired at 12, 24, and 48 h, and STC patient images were acquired at 24, 48, and 72 h. The scores based on the position of the labeling capsules and ROMs in the colon and the colon transit times (CTTs) in the two groups were compared. The CTTs obtained via the ROMs were 34.7±17.4 and 67.3±6.5 h in the healthy controls and STC patients, respectively (P<.05). The CTTs obtained via MRI were 30.9±15.9 and 74.1±7.2 h in the healthy controls and STC patients, respectively (P<.05). The CTTs of the STC patients were significantly longer than the healthy controls. The correlation (r s ) between the scores based on the position of the labeling capsule and ROMs in the healthy group and the STC patients was .880 (P<.05) and .889 (P<.05), respectively. As a MRI contrast label, gadolinium-based capsules exhibit results comparable to ROMs in colon motility measurements. © 2017 John Wiley & Sons Ltd.

Polyethylene glycol and contrast-enhanced MRI of Crohn's disease in children: preliminary experience.

PubMed

Magnano, Gianmichele; Granata, Claudio; Barabino, Arrigo; Magnaguagno, Francesca; Rossi, Umberto; Calevo, Maria Grazia; Toma, Paolo

2003-06-01

To assess the ability of MRI to detect bowel abnormalities in children affected by Crohn's disease (CD). We studied 22 children (age range 8-18 years) referred to us with a known history of CD. MRI was carried out using a 1.5-T unit with a maximum gradient field strength of 16 mT and a phased-array body coil. The sequences performed were breath-hold coronal and axial T2-weighted, express fat saturation, followed by T1-weighted, spoiled gradient, fast fat saturation after IV injection of gadolinium chelate (0.3 mmol/kg) for contrast enhancement of the bowel wall. Bowel distension was achieved using oral administration of isosmotic polyethylene glycol solution. Ileo-colonoscopy was considered the gold standard for evaluation of superficial abnormalities and stenoses of the colon and terminal ileum. MRI findings of bowel-wall thickening, increased vascularisation and extramural involvement were compared with the findings using B-mode and Doppler US. Concordance between MRI and endoscopy, B-mode US and Doppler US findings was determined by the Kappa statistical method. Superficial lesions were not shown by MRI. MR enteroclysis easily detected stenoses, thickening and hyperaemia of bowel wall. Concordance of findings between MRI and endoscopy was 90% (K=0.79, substantial concordance). Concordance of findings between MRI and US concerning bowel-wall thickening and increased vascularisation was 95% (K=0.875, excellent concordance) and 80% (K=0.6, fairly good concordance), respectively. Our initial results show that MRI can detect intra- and extra-mural lesions of CD. The high concordance observed between MRI, endoscopy, US and Doppler US findings suggests that MRI is at least comparable for diagnostic capability with these techniques offering, thanks to multiplanar projections, an improved visualisation of the bowel without ionising radiation.

Enhancing Potentially Plant-Available Lead Concentrations in Contaminated Residential Soils Using a Biodegradable Chelating Agent

NASA Astrophysics Data System (ADS)

Andra, S.; Datta, R.; Sarkar, D.; Saminathan, S.

2007-12-01

Chelation of heavy metals is an important factor in enhancing metal solubility and, hence, metal availability to plants to promote phytoremediation. In the present study, we compared the effects of application of a biodegradable chelating agent, namely, ethylenediaminedisuccinic acid (EDDS) on enhancing plant available form of lead (Pb) in Pb-based paint contaminated residential soils compared to that of a more commonly used, but non-biodegradable chelate, i.e., ethylenediaminetetraacetic acid (EDTA). Development of a successful phytoremediation model for metals such as Pb depends on a thorough understanding of the physical and chemical properties of the soil, along with the optimization of a chelate treatment to mobilize Pb from `unavailable' pools to potentially plant available fraction. In this context, we set out to perform batch incubation experiments to investigate the effectiveness of the two aforementioned chelates in enhancing plant available Pb at four different concentrations (0, 5, 10 and 15 mM/kg soil) and three treatment durations (0, 10 and 30 days). We selected 12 contaminated residential soils from two major metropolitan areas (San Antonio, TX and Baltimore, MD) with varying soil physico-chemical properties - the soils from San Antonio were primarily alkaline and those from Baltimore were typically acidic. Total soil Pb concentrations ranged between 256 mg/kg and 4,182 mg/kg. Our results show that both chelates increased the solubility of Pb, otherwise occluded in the complex soil matrix. For both EDTA and EDDS, the exchangeable concentrations of soil Pb also increased with increase in chelate concentration and incubation time. The most effective treatment was 15 mM chelate kg-1 soil incubated for 30 days, which caused many fold increase in potentially plant available Pb (a combination of the soluble and exchangeable fractions) relative to the unamended controls. Step wise multiple linear regression analysis using chelate-extractable Pb and soil properties showed that plant available Pb fraction could be assessed from the two inter-related soil parameters: soil organic matter and soil pH. Although EDTA was more effective in Pb solubilization than EDDS, the rapid kinetics of the Pb-EDTA complexation process and the prolonged persistence of EDTA in soils pose a potential groundwater contamination problem via metal leaching. In contrast to EDTA, EDDS addition caused relatively slow release of Pb from the soil matrix. The biodegradable nature (and short half life) of EDDS in soils makes it a promising chelating agent for use as soil amendment to enhance Pb solubilization and hence, potential plant uptake.

Ab Initio Assessment of the Thermoelectric Performance of Ruthenium-Doped Gadolinium Orthotantalate

NASA Technical Reports Server (NTRS)

Goldsby, Jon

2016-01-01

Solid state energy harvesting using waste heat available in gas turbine engine, offers potential for power generation to meet growing power needs of aircraft. Thermoelectric material advances offer new opportunities. Weight-optimized integrated turbine engine structure incorporating energy conversion devices.

Novel cardiac magnetic resonance biomarkers: native T1 and extracellular volume myocardial mapping.

PubMed

Cannaò, Paola Maria; Altabella, Luisa; Petrini, Marcello; Alì, Marco; Secchi, Francesco; Sardanelli, Francesco

2016-04-28

Cardiac magnetic resonance (CMR) is a non-invasive diagnostic tool playing a key role in the assessment of cardiac morphology and function as well as in tissue characterization. Late gadolinium enhancement is a fundamental CMR technique for detecting focal or regional abnormalities such as scar tissue, replacement fibrosis, or inflammation using qualitative, semi-quantitative, or quantitative methods, but not allowing for evaluating the whole myocardium in the presence of diffuse disease. The novel T1 mapping approach permits a quantitative assessment of the entire myocardium providing a voxel-by-voxel map of native T1 relaxation time, obtained before the intravenous administration of gadolinium-based contrast material. Combining T1 data obtained before and after contrast injection, it is also possible to calculate the voxel-by-voxel extracellular volume (ECV), resulting in another myocardial parametric map. This article describes technical challenges and clinical perspectives of these two novel CMR biomarkers: myocardial native T1 and ECV mapping.

Retention of Gadolinium-Based Contrast Agents in Multiple Sclerosis: Retrospective Analysis of an 18-Year Longitudinal Study.

PubMed

Forslin, Y; Shams, S; Hashim, F; Aspelin, P; Bergendal, G; Martola, J; Fredrikson, S; Kristoffersen-Wiberg, M; Granberg, T

2017-07-01

Gadolinium-based contrast agents have been associated with lasting high T1-weighted signal intensity in the dentate nucleus and globus pallidus, with histopathologically confirmed gadolinium retention. We aimed to longitudinally investigate the relationship of multiple gadolinium-based contrast agent administrations to the Signal Intensity Index in the dentate nucleus and globus pallidus and any associations with cognitive function in multiple sclerosis. The Signal Intensity Index in the dentate nucleus and globus pallidus was retrospectively evaluated on T1-weighted MR imaging in an 18-year longitudinal cohort study of 23 patients with MS receiving multiple gadolinium-based contrast agent administrations and 23 healthy age- and sex-matched controls. Participants also underwent comprehensive neuropsychological testing. Patients with MS had a higher Signal Intensity Index in the dentate nucleus ( P < .001), but not in the globus pallidus ( P = .19), compared with non-gadolinium-based contrast agent-exposed healthy controls by an unpaired t test. Increasing numbers of gadolinium-based contrast agent administrations were associated with an increased Signal Intensity Index in the dentate nucleus (β = 0.45, P < .001) and globus pallidus (β = 0.60, P < .001). This association remained stable with corrections for the age, disease duration, and physical disability for both the dentate nucleus (β = 0.43, P = .001) and globus pallidus (β = 0.58, P < .001). An increased Signal Intensity Index in the dentate nucleus among patients with MS was associated with lower verbal fluency scores, which remained significant after correction for several aspects of disease severity (β = -0.40 P = .013). Our data corroborate previous reports of lasting gadolinium retention in brain tissues. An increased Signal Intensity Index in the dentate nucleus and globus pallidus was associated with lower verbal fluency, which does not prove causality but encourages further studies on cognition and gadolinium-based contrast agent administration. © 2017 by American Journal of Neuroradiology.

Distribution and chemical forms of gadolinium in the brain: a review.

PubMed

Kanda, Tomonori; Nakai, Yudai; Hagiwara, Akifumi; Oba, Hiroshi; Toyoda, Keiko; Furui, Shigeru

2017-11-01

In the 3 years since residual gadolinium-based contrast agent (GBCA) in the brain was first reported, much has been learned about its accumulation, including the pathway of GBCA entry into the brain, the brain distribution of GBCA and its excretion. Here we review recent progress in understanding the routes of gadolinium deposition in brain structures.

Gadolinium Distribution in Cerebrospinal Fluid after Administration of a Gadolinium-based MR Contrast Agent in Humans.

PubMed

Berger, Florian; Kubik-Huch, Rahel A; Niemann, Tilo; Schmid, Hans Ruedi; Poetzsch, Michael; Froehlich, Johannes M; Beer, Jürg H; Thali, Michael J; Kraemer, Thomas

2018-05-08

Purpose To evaluate whether gadolinium penetrates human cerebrospinal fluid (CSF) after MR imaging (MRI) with a gadolinium-based contrast agent (GBCA). Materials and Methods For this retrospective study, the authors analyzed 60 CSF samples from 57 patients (median age, 50 years; range, 3-92 years) who underwent one contrast material-enhanced MRI examination with gadoterate meglumine within 60 days of CSF extraction between January and December 2016. CSF samples from patients who underwent MRI without contrast material administration (n = 22) or those who underwent contrast-enhanced MRI at least 1 year before extraction (n = 2) were analyzed and used as control samples. CSF measurements were performed with inductively coupled plasma mass spectrometry by monitoring the gadolinium 158 isotope. Statistical analyses were performed by using a preliminary Kruskal-Wallis test. Results Higher CSF gadolinium concentrations were detected within the first 8 hours after GBCA administration (mean concentration, 1152 ng/mL ± 734.6). Concentrations were lower between 8 and 48 hours (872 ng/mL ± 586). After 48 hours, gadolinium was almost completely cleared from CSF (121 ng/mL ± 296.3). All but two samples from the 24 control patients (median age, 60.5 years; range, 19-79 years) were negative for the presence of gadolinium. Those samples were from patients who had undergone GBCA-enhanced MRI examination more than a year before CSF extraction (0.1 and 0.2 ng/mL after 1 and 3 years, respectively). The concentrations in patients with chronic renal insufficiency (n = 3), cerebral toxoplasmosis (n = 1), and liver cirrhosis (n = 1) were higher than the mean concentrations. Conclusion Gadoterate meglumine can be detected in human CSF after intravenous administration. © RSNA, 2018.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wielopolski, L.; Ancona, R.C.; Mossey, R.T.

Hepatic iron stores were measured noninvasively in 31 patients (thalassemia, hemodialysis, hemosiderosis, refractory anemia) with suspected iron overload, employing a nuclear resonance scattering (NRS) technique. The thalassemia patients were undergoing desferrioxamine chelation therapy during the NRS measurements. The hemodialysis patients were measured before chelation therapy. Iron levels measured by NRS were in general agreement with those determined in liver biopsies by atomic absorption spectroscopy. In addition, NRS measurements from the thorax of some of these patients suggest that this method may also prove useful for clinical assessment of cardiac iron.

Alkali metal and alkali earth metal gadolinium halide scintillators

DOEpatents

Bourret-Courchesne, Edith; Derenzo, Stephen E.; Parms, Shameka; Porter-Chapman, Yetta D.; Wiggins, Latoria K.

2016-08-02

The present invention provides for a composition comprising an inorganic scintillator comprising a gadolinium halide, optionally cerium-doped, having the formula A.sub.nGdX.sub.m:Ce; wherein A is nothing, an alkali metal, such as Li or Na, or an alkali earth metal, such as Ba; X is F, Br, Cl, or I; n is an integer from 1 to 2; m is an integer from 4 to 7; and the molar percent of cerium is 0% to 100%. The gadolinium halides or alkali earth metal gadolinium halides are scintillators and produce a bright luminescence upon irradiation by a suitable radiation.

Compensated gadolinium-loaded plastic scintillators for thermal neutron detection (and counting)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dumazert, Jonathan; Coulon, Romain; Bertrand, Guillaume H. V.

2015-07-01

Plastic scintillator loading with gadolinium-rich organometallic complexes shows a high potential for the deployment of efficient and cost-effective neutron detectors. Due to the low-energy photon and electron signature of thermal neutron capture by gadolinium-155 and gadolinium-157, alternative treatment to Pulse Shape Discrimination has to be proposed in order to display a trustable count rate. This paper discloses the principle of a compensation method applied to a two-scintillator system: a detection scintillator interacts with photon radiation and is loaded with gadolinium organometallic compound to become a thermal neutron absorber, while a non-gadolinium loaded compensation scintillator solely interacts with the photon partmore » of the incident radiation. Posterior to the nonlinear smoothing of the counting signals, a hypothesis test determines whether the resulting count rate after photon response compensation falls into statistical fluctuations or provides a robust image of a neutron activity. A laboratory prototype is tested under both photon and neutron irradiations, allowing us to investigate the performance of the overall compensation system in terms of neutron detection, especially with regards to a commercial helium-3 counter. The study reveals satisfactory results in terms of sensitivity and orientates future investigation toward promising axes. (authors)« less

Mercury intracellular partitioning and chelation in a salt marsh plant, Halimione portulacoides (L.) Aellen: strategies underlying tolerance in environmental exposure.

PubMed

Válega, M; Lima, A I G; Figueira, E M A P; Pereira, E; Pardal, M A; Duarte, A C

2009-01-01

In the presence of metal stress, plants can resort to a series of tolerance mechanisms. Therefore field studies should be undertaken in order to evaluate the real role of these mechanisms in stress coping. The aim of this paper was to clarify the biochemical processes behind mercury tolerance in Halimione portulacoides (L.) Aellen (Caryophyllales: Chenopodiaceae) collected in a mercury contaminated salt marsh. Different fractions of mercury were separated: buffer-soluble (mainly cytosolic) and insoluble mercury (mainly associated with membranes and cell walls). The amounts in each fraction of metal were compared and related to metal distribution within plant organs. Protein-mercury complexes were isolated and analysed for their thiol content in order to assess wether the tolerance of this salt marsh plant was associated with the induction of metal chelation by phytochelatins. Overall, the mercury tolerance strategies of the plant are likely to involve root cell wall immobilization as a major mechanism of metal resistance, rather than metal chelation in the cytosolic fraction. Nevertheless, phytochelatins were demonstrated to chelate mercury under environmental exposure.

Synthesis, characterization and in vitro anticancer evaluations of two novel derivatives of deferasirox iron chelator.

PubMed

Salehi, Samie; Saljooghi, Amir Sh; Shiri, Ali

2016-06-15

Iron (Fe) chelation therapy was initially designed to alleviate the toxic effects of excess Fe evident in Fe-overload diseases. However, the novel toxicological properties of some Fe chelator-metal complexes have shifted significant attention to their application in cancer chemotherapy. The present study investigates the new role of deferasirox as an anticancer agent due to its ability to chelate with iron. Because of aminoacids antioxidant effect, deferasirox and its two novel amino acid derivatives have been synthesized through the treatment of deferasirox with DCC as well as glycine or phenylalanine methyl ester. All new compounds have been characterized by elemental analysis, FT-IR NMR and mass spectrometry. Therefore, the cytotoxicity of these compounds was screened for antitumor activity against some cell lines using cisplatin as a comparative standard by MTT assay and Flow cytometry. The impact of iron in the intracellular generation of reactive oxygen species was assessed on HT29 and MDA-MB-231 cells. The potential of the synthesized iron chelators for their efficacy to protect cells against model oxidative injury induced was compared. The reactive oxygen species intracellular fluorescence intensity were measured and the result showed that the reactive oxygen species intensity after iron incubation increased while after chelators incubation the reactive oxygen species intensity were decreased significantly. Besides, the effect of the synthesized compounds on mouse fibroblast cell line (L929) was simultaneously evaluated as control. The pharmacological results showed that deferasirox and its two novel aminoacid derivatives were potent anticancer agents. Copyright © 2016 Elsevier B.V. All rights reserved.

Theoretical analysis of the influence of chelate-ring size and vicinal effects on electronic circular dichroism spectra of cobalt(III) EDDA-type complexes.

PubMed

Wang, Ai; Wang, Yuekui; Jia, Jie; Feng, Lixia; Zhang, Chunxia; Liu, Linlin

2013-06-20

To assess the contributions of configurational and vicinal effects as well as chelate-ring size to rotational strengths, the geometries of a series of cobalt(III) complexes [Co(EDDA-type)(L)](±) with the tetradentate EDDA-type ligands, EDDA (ethylenediamine-N,N'-diacetate), DMEDDA (N,N'-dimethylethylenediamine-N,N'-diacetate), DEEDDA (N,N'-diethylethylenediamine-N,N'-diacetate), and a bidentate ancillary ligand L (L = ethylenediamine, oxalate, carbonate, (S)-alanine, and malonate) in aqueous solution have been optimized at the DFT/B3LYP/6-311++G(2d,p) level of theory. Based on the optimized geometries, the excitation energies and oscillator and rotational strengths have been calculated using the time-dependent density functional theory (TDDFT) method with the same functional and basis set. The calculated circular dichroism (CD) curves are in excellent agreement with the observed ones except for some small red or blue shifts in peak wavelengths. For the influence of chelate-ring size of the bidentate ligands on the CD intensities, a qualitative analysis together with the quantitative TDDFT calculation reveal that it depends on the symmetry of the cobalt-EDDA backbone. For the s-cis-isomers, the influence is negligible due to the perturbation is symmetric. For the uns-cis-isomers, the perturbation is unsymmetric. Since a small ring size means a large perturbation, this leads to the integral CD intensities decreasing with increasing the chelate ring size. The vicinal effects of asymmetric nitrogens incorporate both the substitutent effects and conformational relaxation effects, with the former being dominant. By analyzing the contributions of chiral arrays to rotational strengths, we found that the part of contributions dominated by the S-type chiral nitrogens could be considered as a good measure for the vicinal effects of chiral nitrogens. In addition, we found that the twist form (δ/λ) of the backbone ethylenediamine ring (E-ring) of the coordinated EDDA-type ligands is a key factor to understand the properties of these chelates, because it not only dominates the relative stabilities of the s-cis-Λ(SS)-diastereoisomers with the result that λ > δ but also affects the major CD band by changing the order of the first two transitions. Moreover, the twist angle of E-ring is inversely related to the vicinal effect of chiral nitrogens. These findings may help us to understand the chelate ring size as well as vicinal effect related chiroptical phenomenon of the cobalt EDDA-type chelates.

Safety assessment of nanoparamagnetic contrast agents with different coatings for molecular MRI

NASA Astrophysics Data System (ADS)

Azizian, Gholamreza; Riyahi-Alam, Nader; Haghgoo, Soheila; Saffari, Mojtaba; Zohdiaghdam, Reza; Gorji, Ensieh

2013-04-01

Despite the wide application of gadolinium as a contrast agent for magnetic resonance imaging (MRI), there is a serious lack of information on its toxicity. Gadolinium and gadolinium oxide (Gd-oxide) are used as contrast agents for magnetic resonance imaging (MRI). There are methods for reducing toxicity of these materials, such as core nanoparticles coating or conjugating. Therefore, for toxicity evaluation, we compared the viability of commercial contrast agents in MRI (Gd-DTPA) and three nanoparticles with the same core Gd2O3 and small particulate gadolinium oxide or SPGO (< 40 nm) but different coatings of diethyleneglycol (DEG) as Gd2O3-DEG and methoxy polyethylene glycol-silane (mPEG-silane: 550 and 2000 Dalton) as SPGO-mPEG-silane550 and SPGO-mPEG-silane2000, respectively, in the SK-MEL3 cell line, by light microscopy, MTT assay using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide, and the LDH assay detecting lactate dehydrogenase activity. The viability values were not statistically different between the three nanoparticles and Gd-DTPA. The MTT and LDH assay results showed that Gd2O3-DEG nanoparticles were more toxic than Gd-DTPA and other nanoparticles. Also, SPGO-mPEG-silane2000 was more biocompatible than other nanoparticles. The obtained results did not show any significant increase in cytotoxicity of the nanoparticles and Gd-DTPA, neither dose-dependent nor time-dependent. Therefore, DEG and PEG, due to their considerable properties and irregular sizes (different molecular weights), were selected as the useful surface covering materials of nanomagnetic particles that could reveal noticeable relaxivity and biocompatibility characteristics.

Revised Recommendations of the Consortium of MS Centers Task Force for a Standardized MRI Protocol and Clinical Guidelines for the Diagnosis and Follow-Up of Multiple Sclerosis

PubMed Central

Traboulsee, A.; Simon, J.H.; Stone, L.; Fisher, E.; Jones, D.E.; Malhotra, A.; Newsome, S.D.; Oh, J.; Reich, D.S.; Richert, N.; Rammohan, K.; Khan, O.; Radue, E.-W.; Ford, C.; Halper, J.; Li, D.

2016-01-01

SUMMARY An international group of neurologists and radiologists developed revised guidelines for standardized brain and spinal cord MR imaging for the diagnosis and follow-up of MS. A brain MR imaging with gadolinium is recommended for the diagnosis of MS. A spinal cord MR imaging is recommended if the brain MR imaging is nondiagnostic or if the presenting symptoms are at the level of the spinal cord. A follow-up brain MR imaging with gadolinium is recommended to demonstrate dissemination in time and ongoing clinically silent disease activity while on treatment, to evaluate unexpected clinical worsening, to re-assess the original diagnosis, and as a new baseline before starting or modifying therapy. A routine brain MR imaging should be considered every 6 months to 2 years for all patients with relapsing MS. The brain MR imaging protocol includes 3D T1-weighted, 3D T2-FLAIR, 3D T2-weighted, post-single-dose gadolinium-enhanced T1-weighted sequences, and a DWI sequence. The progressive multifocal leukoencephalopathy surveillance protocol includes FLAIR and DWI sequences only. The spinal cord MR imaging protocol includes sagittal T1-weighted and proton attenuation, STIR or phase-sensitive inversion recovery, axial T2- or T2*-weighted imaging through suspicious lesions, and, in some cases, postcontrast gadolinium-enhanced T1-weighted imaging. The clinical question being addressed should be provided in the requisition for the MR imaging. The radiology report should be descriptive, with results referenced to previous studies. MR imaging studies should be permanently retained and available. The current revision incorporates new clinical information and imaging techniques that have become more available. PMID:26564433

Survey of gadolinium-based contrast agent utilization among the members of the Society for Pediatric Radiology: a Quality and Safety Committee report.

PubMed

Blumfield, Einat; Moore, Michael M; Drake, Mary K; Goodman, Thomas R; Lewis, Kristopher N; Meyer, Laura T; Ngo, Thang D; Sammet, Christina; Stanescu, Arta Luana; Swenson, David W; Slovis, Thomas L; Iyer, Ramesh S

2017-05-01

Gadolinium-based contrast agents (GBCAs) have been used for magnetic resonance (MR) imaging over the last three decades. Recent reports demonstrated gadolinium retention in patients' brains following intravenous administration. Since gadolinium is a highly toxic heavy metal, there is a potential for adverse effects from prolonged retention or deposition, particularly in children. For this reason, the Society (SPR) for Pediatric Radiology Quality and Safety committee conducted a survey to evaluate the current status of GBCAs usage among pediatric radiologists. To assess the usage of GBCAs among SPR members. An online 15-question survey was distributed to SPR members. Survey questions pertained to the type of GBCAs used, protocoling workflow, requirement of renal function or pregnancy tests, and various clinical indications for contrast-enhanced MRI examinations. A total of 163 survey responses were compiled (11.1% of survey invitations), the majority of these from academic institutions in the United States. Ninety-four percent reported that MR studies are always or usually protocoled by pediatric radiologists. The most common GBCA utilized by survey respondents were Eovist (60.7%), Ablavar (45.4%), Gadovist (38.7%), Magnevist (34.4%) and Dotarem (32.5%). For several clinical indications, survey responses regarding GBCA administration were concordant with American College of Radiology (ACR) Appropriateness Criteria, including seizures, headache and osteomyelitis. For other indications, including growth hormone deficiency and suspected vascular ring, survey responses revealed potential overutilization of GBCAs when compared to ACR recommendations. Survey results demonstrate that GBCAs are administered judiciously in children, yet there is an opportunity to improve their utilization with the goal of reducing potential future adverse effects.

Modeling the effect of succimer (DMSA; dimercaptosuccinic acid) chelation therapy in patients poisoned by lead.

PubMed

van Eijkeren, Jan C H; Olie, J Daniël N; Bradberry, Sally M; Vale, J Allister; de Vries, Irma; Clewell, Harvey J; Meulenbelt, Jan; Hunault, Claudine C

2017-02-01

Kinetic models could assist clinicians potentially in managing cases of lead poisoning. Several models exist that can simulate lead kinetics but none of them can predict the effect of chelation in lead poisoning. Our aim was to devise a model to predict the effect of succimer (dimercaptosuccinic acid; DMSA) chelation therapy on blood lead concentrations. We integrated a two-compartment kinetic succimer model into an existing PBPK lead model and produced a Chelation Lead Therapy (CLT) model. The accuracy of the model's predictions was assessed by simulating clinical observations in patients poisoned by lead and treated with succimer. The CLT model calculates blood lead concentrations as the sum of the background exposure and the acute or chronic lead poisoning. The latter was due either to ingestion of traditional remedies or occupational exposure to lead-polluted ambient air. The exposure duration was known. The blood lead concentrations predicted by the CLT model were compared to the measured blood lead concentrations. Pre-chelation blood lead concentrations ranged between 99 and 150 μg/dL. The model was able to simulate accurately the blood lead concentrations during and after succimer treatment. The pattern of urine lead excretion was successfully predicted in some patients, while poorly predicted in others. Our model is able to predict blood lead concentrations after succimer therapy, at least, in situations where the duration of lead exposure is known.

Iron-chelating effect of silymarin in patients with β-thalassemia major: A crossover randomised control trial.

PubMed

Darvishi-Khezri, Hadi; Salehifar, Ebrahim; Kosaryan, Mehrnoush; Karami, Hossein; Mahdavi, Mohammadreza; Alipour, Abbas; Aliasgharian, Aily

2018-03-01

This study aimed to determine the potential iron-chelating effects of silymarin in patients with β-thalassemia major receiving standard iron-chelation therapy. We evaluated whether addition of silymarin to standard iron-chelation therapy could improve iron burden markers and liver and cardiac function in these patients, via a placebo-controlled, crossover clinical study. Silymarin (140 mg) or placebo were administered thrice daily to all patients (n = 82) for 12 weeks, and after a 2-week washout period, patients were crossed over to the other groups. Silymarin efficacy was assessed by measuring serum iron level, ferritin level, total iron-binding capacity and liver and cardiac function on magnetic resonance imaging. Silymarin treatment resulted in a negative change in the serum iron and ferritin levels and a positive change in the total iron-binding capacity levels (treatment effect, p < .001, p = .06, and p = .05, respectively). Silymarin treatment led to positive changes in cardiac and liver function in both treatment sequences of study; however, this was not statistically significant. There was a negative change in liver iron concentration in both treatment sequences (treatment effect, p = .02). In conclusion, combined iron-chelation and silymarin therapy was effective for improving the iron-burden status in patients with β-thalassemia major. Copyright © 2017 John Wiley & Sons, Ltd.

ZnO:Gd nanocrystals for fluorescent applications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Divya, N. K., E-mail: divyank90@gmail.com; Pradyumnan, P. P.

2016-05-23

Gadolinium doped ZnO crystals within the solubility limit of gadolinium in ZnO matrix were prepared by solid state reaction technique. The method is relatively less expense and enables the production in large scale. The samples were characterised by X-ray diffraction (XRD), energy dispersive X-ray spectroscopy (EDS), scanning electron microscopy (SEM), UV/Vis diffuse reflectance spectroscopy and photoluminescence techniques. Fluorescent property studies of gadolinium doped ZnO at room temperature show enhanced visible light emission due to the defects and oxygen vacancies produced via doping. This work reports the impact of gadolinium doping in the structural, optical and luminescent properties of ZnO inmore » detail.« less

Are gadolinium-based contrast media nephrotoxic? A renal biopsy study.

PubMed

Akgun, Hulya; Gonlusen, Gulfiliz; Cartwright, Joiner; Suki, Wadi N; Truong, Luan D

2006-09-01

Gadolinium-based contrast media were originally introduced as alternatives to iodinated media for magnetic resonance imaging. Although originally thought to be nonnephrotoxic, gadolinium-based contrast media have recently been reported to be associated with acute renal failure; the mechanism and the underlying renal injury are not completely understood. We report what is, to our knowledge, the first renal biopsy in this context. A 56-year-old patient underwent 2 consecutive vascular imaging procedures in conjunction with gadolinium-based contrast medium administration. A few days later, the patient developed acute renal failure. A renal biopsy showed acute tubular cell injury including patchy tubular cell necrosis, tubular cell degeneration, and marked proliferation of tubular cells, together with mild interstitial edema and interstitial inflammation, but without significant glomerular or vascular changes. During supportive therapy, renal function was partially regained. This case emphasizes the potential nephrotoxicity of gadolinium-based contrast media and suggests that the nephrotoxicity is related to potentially reversible acute tubular cell injury.

Fluid extraction using carbon dioxide and organophosphorus chelating agents

DOEpatents

Smart, N.G.; Wai, C.M.; Lin, Y.; Kwang, Y.H.

1998-11-24

Methods for extracting metalloid and metal species from a solid or liquid material by exposing the material to a fluid solvent, particularly supercritical CO{sub 2}, and a chelating agent are described. The chelating agent forms a chelate with the species, the chelate being soluble in the fluid to allow removal of the species from the material. In preferred embodiments the extraction solvent is supercritical CO{sub 2} and the chelating agent comprises an organophosphorous chelating agent, particularly sulfur-containing organophosphorous chelating agents, including mixtures of chelating agents. Examples of chelating agents include monothiophosphinic acid, di-thiophosphinic acid, phosphine sulfite, phosphorothioic acid, and mixtures thereof. The method provides an environmentally benign process for removing metal and metalloids from industrial waste solutions, particularly acidic solutions. Both the chelate and the supercritical fluid can be regenerated and the contaminant species recovered to provide an economic, efficient process. 1 fig.

Fluid extraction using carbon dioxide and organophosphorus chelating agents

DOEpatents

Smart, Neil G.; Wai, Chien M.; Lin, Yuehe; Kwang, Yak Hwa

1998-01-01

Methods for extracting metalloid and metal species from a solid or liquid material by exposing the material to a fluid solvent, particularly supercritical CO.sub.2, and a chelating agent are described. The chelating agent forms a chelate with the species, the chelate being soluble in the fluid to allow removal of the species from the material. In preferred embodiments the extraction solvent is supercritical CO.sub.2 and the chelating agent comprises an organophosphorous chelating agent, particularly sulfur-containing organophosphorous chelating agents, including mixtures of chelating agents. Examples of chelating agents include monothiophosphinic acid, di-thiophosphinic acid, phosphine sulfite, phosphorothioic acid, and mixtures thereof. The method provides an environmentally benign process for removing metal and metalloids from industrial waste solutions, particularly acidic solutions. Both the chelate and the supercritical fluid can be regenerated and the contaminant species recovered to provide an economic, efficient process.

In vitro study of novel gadolinium-loaded liposomes guided by GBI-10 aptamer for promising tumor targeting and tumor diagnosis by magnetic resonance imaging.

PubMed

Gu, Meng-Jie; Li, Kun-Feng; Zhang, Lan-Xin; Wang, Huan; Liu, Li-Si; Zheng, Zhuo-Zhao; Han, Nan-Yin; Yang, Zhen-Jun; Fan, Tian-Yuan

2015-01-01

Novel gadolinium-loaded liposomes guided by GBI-10 aptamer were developed and evaluated in vitro to enhance magnetic resonance imaging (MRI) diagnosis of tumor. Nontargeted gadolinium-loaded liposomes were achieved by incorporating amphipathic material, Gd (III) [N,N-bis-stearylamidomethyl-N'-amidomethyl] diethylenetriamine tetraacetic acid, into the liposome membrane using lipid film hydration method. GBI-10, as the targeting ligand, was then conjugated onto the liposome surface to get GBI-10-targeted gadolinium-loaded liposomes (GTLs). Both nontargeted gadolinium-loaded liposomes and GTLs displayed good dispersion stability, optimal size, and zeta potential for tumor targeting, as well as favorable imaging properties with enhanced relaxivity compared with a commercial MRI contrast agent (CA), gadopentetate dimeglumine. The use of GBI-10 aptamer in this liposomal system was intended to result in increased accumulation of gadolinium at the periphery of C6 glioma cells, where the targeting extracellular matrix protein tenascin-C is overexpressed. Increased cellular binding of GTLs to C6 cells was confirmed by confocal microscopy, flow cytometry, and MRI, demonstrating the promise of this novel delivery system as a carrier of MRI contrast agent for the diagnosis of tumor. These studies provide a new strategy furthering the development of nanomedicine for both diagnosis and therapy of tumor.

Tracing gadolinium-based contrast agents from surface water to drinking water by means of speciation analysis.

PubMed

Birka, Marvin; Wehe, Christoph A; Hachmöller, Oliver; Sperling, Michael; Karst, Uwe

2016-04-01

In recent decades, a significant amount of anthropogenic gadolinium has been released into the environment as a result of the broad application of contrast agents for magnetic resonance imaging (MRI). Since this anthropogenic gadolinium anomaly has also been detected in drinking water, it has become necessary to investigate the possible effect of drinking water purification on these highly polar microcontaminats. Therefore, a novel highly sensitive method for speciation analysis of gadolinium is presented. For that purpose, the hyphenation of hydrophilic interaction liquid chromatography (HILIC) and inductively coupled plasma-mass spectrometry (ICP-MS) was employed. In order to enhance the detection power, sample introduction was carried out by ultrasonic nebulization. In combination with a novel HILIC method using a diol-based stationary phase, it was possible to achieve superior limits of detection for frequently applied gadolinium-based contrast agents below 20pmol/L. With this method, the contrast agents Gd-DTPA, Gd-DOTA and Gd-BT-DO3A were determined in concentrations up to 159pmol/L in samples from several waterworks in a densely populated region of Germany alongside the river Ruhr as well as from a waterworks near a catchment lake. Thereby, the direct impact of anthropogenic gadolinium species being present in the surface water on the amount of anthropogenic gadolinium in drinking water was shown. There was no evidence for the degradation of contrast agents, the release of Gd(3+) or the presence of further Gd species. Copyright © 2016 Elsevier B.V. All rights reserved.

Imaging transplanted stem cells in real time using an MRI dual-contrast method

PubMed Central

Ngen, Ethel J.; Wang, Lee; Kato, Yoshinori; Krishnamachary, Balaji; Zhu, Wenlian; Gandhi, Nishant; Smith, Barbara; Armour, Michael; Wong, John; Gabrielson, Kathleen; Artemov, Dmitri

2015-01-01

Stem cell therapies are currently being investigated for the repair of brain injuries. Although exogenous stem cell labelling with superparamagnetic iron oxide nanoparticles (SPIONs) prior to transplantation provides a means to noninvasively monitor stem cell transplantation by magnetic resonance imaging (MRI), monitoring cell death is still a challenge. Here, we investigate the feasibility of using an MRI dual-contrast technique to detect cell delivery, cell migration and cell death after stem cell transplantation. Human mesenchymal stem cells were dual labelled with SPIONs and gadolinium-based chelates (GdDTPA). The viability, proliferation rate, and differentiation potential of the labelled cells were then evaluated. The feasibility of this MRI technique to distinguish between live and dead cells was next evaluated using MRI phantoms, and in vivo using both immune-competent and immune-deficient mice, following the induction of brain injury in the mice. All results were validated with bioluminescence imaging. In live cells, a negative (T2/T2*) MRI contrast predominates, and is used to track cell delivery and cell migration. Upon cell death, a diffused positive (T1) MRI contrast is generated in the vicinity of the dead cells, and serves as an imaging marker for cell death. Ultimately, this technique could be used to manage stem cell therapies. PMID:26330231

Twisting integrin receptors increases endothelin-1 gene expression in endothelial cells

NASA Technical Reports Server (NTRS)

Chen, J.; Fabry, B.; Schiffrin, E. L.; Wang, N.; Ingber, D. E. (Principal Investigator)

2001-01-01

A magnetic twisting stimulator was developed based on the previously published technique of magnetic twisting cytometry. Using ligand-coated ferromagnetic microbeads, this device can apply mechanical stresses with varying amplitudes, duration, frequencies, and waveforms to specific cell surface receptors. Biochemical and biological responses of the cells to the mechanical stimulation can be assayed. Twisting integrin receptors with RGD (Arg-Gly-Asp)-containing peptide-coated beads increased endothelin-1 (ET-1) gene expression by >100%. In contrast, twisting scavenger receptors with acetylated low-density lipoprotein-coated beads or twisting HLA antigen with anti-HLA antibody-coated beads did not lead to alterations in ET-1 gene expression. In situ hybridization showed that the increase in ET-1 mRNA was localized in the cells that were stressed with the RGD-coated beads. Blocking stretch-activated ion channels with gadolinium, chelating Ca2+ with EGTA, or inhibiting tyrosine phosphorylation with genistein abolished twist-induced ET-1 mRNA elevation. Abolishing cytoskeletal tension with an inhibitor of the myosin ATPase, with an inhibitor of myosin light chain kinase, or with an actin microfilament disrupter blocked twisted-induced increases in ET-1 expression. Our results are consistent with the hypothesis that the molecular structural linkage of integrin-cytoskeleton is an important pathway for stress-induced ET-1 gene expression.

Producing >60,000-fold room-temperature 89Y NMR signal enhancement

NASA Astrophysics Data System (ADS)

Lumata, Lloyd; Jindal, Ashish; Merritt, Matthew; Malloy, Craig; Sherry, A. Dean; Kovacs, Zoltan

2011-03-01

89 Y in chelated form is potentially valuable in medical imaging because its chemical shift is sensitive to local factors in tumors such as pH. However, 89 Y has a low gyromagnetic ratio γn thus its NMR signal is hampered by low thermal polarization. Here we show that we can enhance the room-temperature NMR signal of 89 Y up to 65,000 times the thermal signal, which corresponds to 10 % nuclear polarization, via fast dissolution dynamic nuclear polarization (DNP). The relatively long spin-lattice relaxation time T1 (~ 500 s) of 89 Y translates to a long polarization lifetime. The 89 Y NMR enhancement is optimized by varying the glassing matrices and paramagnetic agents as well as doping the samples with a gadolinium relaxation agent. Co-polarization of 89 Y-DOTA with a 13 C sample shows that both nuclear spin species acquire the same spin temperature Ts , consistent with thermal mixing mechanism of DNP. The high room-temperature NMR signal enhancement places 89 Y, one of the most challenging nuclei to detect by NMR, in the list of viable magnetic resonance imaging (MRI) agents when hyperpolarized under optimized conditions. This work is supported in part by the National Institutes of Health grant numbers 1R21EB009147-01 and RR02584.

Imaging transplanted stem cells in real time using an MRI dual-contrast method.

PubMed

Ngen, Ethel J; Wang, Lee; Kato, Yoshinori; Krishnamachary, Balaji; Zhu, Wenlian; Gandhi, Nishant; Smith, Barbara; Armour, Michael; Wong, John; Gabrielson, Kathleen; Artemov, Dmitri

2015-09-02

Stem cell therapies are currently being investigated for the repair of brain injuries. Although exogenous stem cell labelling with superparamagnetic iron oxide nanoparticles (SPIONs) prior to transplantation provides a means to noninvasively monitor stem cell transplantation by magnetic resonance imaging (MRI), monitoring cell death is still a challenge. Here, we investigate the feasibility of using an MRI dual-contrast technique to detect cell delivery, cell migration and cell death after stem cell transplantation. Human mesenchymal stem cells were dual labelled with SPIONs and gadolinium-based chelates (GdDTPA). The viability, proliferation rate, and differentiation potential of the labelled cells were then evaluated. The feasibility of this MRI technique to distinguish between live and dead cells was next evaluated using MRI phantoms, and in vivo using both immune-competent and immune-deficient mice, following the induction of brain injury in the mice. All results were validated with bioluminescence imaging. In live cells, a negative (T2/T2*) MRI contrast predominates, and is used to track cell delivery and cell migration. Upon cell death, a diffused positive (T1) MRI contrast is generated in the vicinity of the dead cells, and serves as an imaging marker for cell death. Ultimately, this technique could be used to manage stem cell therapies.

Gadolinium accumulation in organs of Sprague-Dawley® rats after implantation of a biodegradable magnesium-gadolinium alloy.

PubMed

Myrissa, Anastasia; Braeuer, Simone; Martinelli, Elisabeth; Willumeit-Römer, Regine; Goessler, Walter; Weinberg, Annelie Martina

2017-01-15

Biodegradable magnesium implants are under investigation because of their promising properties as medical devices. For enhancing the mechanical properties and the degradation resistance, rare earth elements are often used as alloying elements. In this study Mg10Gd pins were implanted into Sprague-Dawley® rats. The pin volume loss and a possible accumulation of magnesium and gadolinium in the rats' organs and blood were investigated in a long-term study over 36weeks. The results showed that Mg10Gd is a fast disintegrating material. Already 12weeks after implantation the alloy is fragmented to smaller particles, which can be found within the intramedullary cavity and the cortical bones. They disturbed the bone remodeling until the end of the study. The results concerning the elements' distribution in the animals' bodies were even more striking, since an accumulation of gadolinium could be observed in the investigated organs over the whole time span. The most affected tissue was the spleen, with up to 3240μgGd/kg wet mass, followed by the lung, liver and kidney (up to 1040, 685 and 207μgGd/kg). In the brain, muscle and heart, the gadolinium concentrations were much smaller (less than 20μg/kg), but an accumulation could still be detected. Interestingly, blood serum samples showed no accumulation of magnesium and gadolinium. This is the first time that an accumulation of gadolinium in animal organs was observed after the application of a gadolinium-containing degradable magnesium implant. These findings demonstrate the importance of future investigations concerning the distribution of the constituents of new biodegradable materials in the body, to ensure the patients' safety. In the last years, biodegradable Mg alloys are under investigation due to their promising properties as orthopaedic devices used for bone fracture stabilization. Gadolinium as Rare Earth Element enhances the mechanical properties of Mg-Gd alloys but its toxicity in humans is still questionable. Up to now, there is no study investigating the elements' metabolism of a REE-containing Magnesium alloy in an animal model. In this study, we examined the gadolinium distribution and accumulation in rat organs during the degradation of Mg10Gd. Our findings showed that Gd is accumulating in the animal organs, especially in spleen, liver and kidney. This study is of crucial benefit regarding a safe application of REE-containing Magnesium alloys in humans. Copyright © 2016. Published by Elsevier Ltd.

Magnetic resonance and confocal imaging of solute penetration into the lens reveals a zone of restricted extracellular space diffusion.

PubMed

Vaghefi, Ehsan; Walker, Kerry; Pontre, Beau P; Jacobs, Marc D; Donaldson, Paul J

2012-06-01

It has been proposed that in the absence of blood supply, the ocular lens operates an internal microcirculation system that delivers nutrients to internalized fiber cells faster and more efficiently than would occur by passive diffusion alone. To visualize the extracellular space solute fluxes potentially generated by this system, bovine lenses were organ cultured in artificial aqueous humor (AAH) for 4 h in the presence or absence of two gadolinium-based contrast agents, ionic Gd(3+), or a chelated form of Gd(3+), Gd-diethylenetriamine penta-acetic acid (Gd-DTPA; mol mass = 590 Da). Contrast reagent penetration into the lens core was monitored in real time using inversion recovery-spin echo (IR-SE) magnetic resonance imaging (MRI), while steady-state accumulation of [Gd-DTPA](-2) was also determined by calculating T1 values. After incubation, lenses were fixed and cryosectioned, and sections were labeled with the membrane marker wheat germ agglutinin (WGA). Sections were imaged by confocal microscopy using standard and reflectance imaging modalities to visualize the fluorescent WGA label and gadolinium reagents, respectively. Real-time IR-SE MRI showed rapid penetration of Gd(3+) into the outer cortex of the lens and a subsequent bloom of signal in the core. These two areas of signal were separated by an area in the inner cortex that limited entry of Gd(3+). Similar results were obtained for Gd-DTPA, but the penetration of the larger negatively charged molecule into the core could only be detected by calculating T1 values. The presence of Gd-DTPA in the extracellular space of the outer cortex and core, but its apparent absence from the inner cortex was confirmed using reflectance imaging of equatorial sections. In axial sections, Gd-DTPA was associated with the sutures, suggesting these structures provide a pathway from the surface, across the inner cortex barrier to the lens core. Our studies have revealed inner and outer boundaries of a zone within which a narrowing of the extracellular space restricts solute diffusion and acts to direct fluxes into the lens core via the sutures.

Liposome encapsulation of chelating agents

DOEpatents

Rahman, Yueh Erh

1976-01-13

A method for transferring a chelating agent across a cellular membrane by encapsulating the charged chelating agent within liposomes and carrying the liposome-encapsulated chelating agent to the cellular membrane where the liposomes containing the chelating agent will be taken up by the cells, thereby transferring the chelating agent across the cellular membrane. A chelating agent can be introduced into the interior of a cell of a living organism wherein the liposomes will be decomposed, releasing the chelating agent to the interior of the cell. The released chelating agent will complex intracellularly deposited toxic heavy metals, permitting the more soluble metal complex to transfer across the cellular membrane from the cell and subsequently be removed from the living organism.

Chelation technology: a promising green approach for resource management and waste minimization.

PubMed

Chauhan, Garima; Pant, K K; Nigam, K D P

2015-01-01

Green chemical engineering recognises the concept of developing innovative environmentally benign technologies to protect human health and ecosystems. In order to explore this concept for minimizing industrial waste and for reducing the environmental impact of hazardous chemicals, new greener approaches need to be adopted for the extraction of heavy metals from industrial waste. In this review, a range of conventional processes and new green approaches employed for metal extraction are discussed in brief. Chelation technology, a modern research trend, has shown its potential to develop sustainable technology for metal extraction from various metal-contaminated sites. However, the interaction mechanism of ligands with metals and the ecotoxicological risk associated with the increased bioavailability of heavy metals due to the formation of metal-chelant complexes is still not sufficiently explicated in the literature. Therefore, a need was felt to provide a comprehensive state-of-the-art review of all aspects associated with chelation technology to promote this process as a green chemical engineering approach. This article elucidates the mechanism and thermodynamics associated with metal-ligand complexation in order to have a better understanding of the metal extraction process. The effects of various process parameters on the formation and stability of complexes have been elaborately discussed with respect to optimizing the chelation efficiency. The non-biodegradable attribute of ligands is another important aspect which is currently of concern. Therefore, biotechnological approaches and computational tools have been assessed in this review to illustrate the possibility of ligand degradation, which will help the readers to look for new environmentally safe mobilizing agents. In addition, emerging trends and opportunities in the field of chelation technology have been summarized and the diverse applicability of chelation technology in metal extraction from contaminated sites has also been reviewed.

EDTA Chelation Therapy Alone and in Combination with Oral High-Dose Multivitamins and Minerals for Coronary Disease: The Factorial Group Results of the Trial to Assess Chelation Therapy

PubMed Central

Lamas, Gervasio A.; Boineau, Robin; Goertz, Christine; Mark, Daniel B.; Rosenberg, Yves; Stylianou, Mario; Rozema, Theodore; Nahin, Richard L.; Chappell, L. Terry; Lindblad, Lauren; Lewis, Eldrin F.; Drisko, Jeanne; Lee, Kerry L.

2014-01-01

Background Disodium ethylene diamine tetraacetic acid (EDTA) reduced adverse cardiac outcomes in a factorial trial also testing oral vitamins. Objective This report describes the intent-to-treat comparison of the 4 factorial groups overall and in patients with diabetes. Methods Double-blind placebo-controlled 2 × 2 factorial multicenter randomized trial of 1708 post-MI patients ≥ 50 years and creatinine ≤2.0 mg/dL randomized to receive 40 EDTA chelation or placebo infusions plus 6 caplets daily of a 28-component multivitaminmultimineral mixture or placebo. Primary endpoint was a composite of total mortality, MI, stroke, coronary revascularization, or hospitalization for angina. Results Median age was 65 years, 18% female, 94% Caucasian, 37% diabetic, 83% prior coronary revascularization, and 73% on statins. Five-year Kaplan-Meier estimates for the primary endpoint in the chelation + high-dose vitamin group was 31.9%, in the chelation + placebo vitamin group 33.7%, in the placebo infusion + active vitamin group 36.6%, and in the placebo infusions + placebo vitamin group 40.2 %. The reduction in primary endpoint by double active treatment compared with double placebo was significant (HR 0.74, 95% CI (0.57,0.95); p=0.016). In patients with diabetes, the primary endpoint reduction of double active compared with double placebo was more pronounced (HR 0.49, 95% CI (0.33,0.75), p<0.001). Conclusions In stable post- MI patients on evidence-based medical therapy, the combination of oral high-dose vitamins and chelation therapy compared with double placebo reduced clinically important cardiovascular events to an extent that was both statistically significant and of potential clinical relevance. PMID:24952858

The Effect of an EDTA-based Chelation Regimen on Patients with Diabetes and Prior Myocardial Infarction in TACT

PubMed Central

Escolar, Esteban; Lamas, Gervasio A.; Mark, Daniel B.; Boineau, Robin; Goertz, Christine; Rosenberg, Yves; Nahin, Richard L.; Ouyang, Pamela; Rozema, Theodore; Magaziner, Allan; Nahas, Richard; Lewis, Eldrin F.; Lindblad, Lauren; Lee, Kerry L.

2014-01-01

Background The Trial to Assess Chelation Therapy (TACT) showed clinical benefit of an ethylene diamine tetraacetic acid (EDTA-based) infusion regimen in patients 50 years or older with prior myocardial infarction (MI). Diabetes prior to enrollment was a pre-specified subgroup. Methods and Results Patients received 40 infusions of EDTA chelation or placebo. 633 (37%) had diabetes (322 EDTA, 311 placebo). EDTA reduced the primary endpoint (death, reinfarction, stroke, coronary revascularization, or hospitalization for angina) [25% vs 38%, hazard ratio (HR) 0.59, 95% confidence interval (CI) (0.44, 0.79), p<0.001] over 5 years. The result remained significant after Bonferroni adjustment for multiple subgroups (99.4% CI (0.39, 0.88), adjusted p=0.002). All-cause mortality was reduced by EDTA chelation [10% vs 16%, HR 0.57, 95% CI (0.36, 0.88) p=0.011], as was the secondary endpoint (cardiovascular death, reinfarction, or stroke) [11% vs 17% HR 0.60, 95% CI (0.39, 0.91), p=0.017]. After adjusting for multiple subgroups, however, those results were no longer significant. The number needed to treat to reduce one primary endpoint was 6.5 over 5 years (95% CI (4.4, 12.7). There was no reduction in events in non-diabetics (n=1075, p=0.877), resulting in a treatment by diabetes interaction (p=0.004). Conclusions Post-MI diabetic patients age 50 or older demonstrated a marked reduction in cardiovascular events with EDTA chelation. These findings support efforts to replicate these findings and define the mechanisms of benefit. They do not, however, constitute sufficient evidence to indicate the routine use of chelation therapy for all post-MI diabetic patients. PMID:24254885

Profound Morphological Changes in the Erythrocytes and Fibrin Networks of Patients with Hemochromatosis or with Hyperferritinemia, and Their Normalization by Iron Chelators and Other Agents

PubMed Central

Pretorius, Etheresia; Bester, Janette; Vermeulen, Natasha; Lipinski, Boguslaw; Gericke, George S.; Kell, Douglas B.

2014-01-01

It is well-known that individuals with increased iron levels are more prone to thrombotic diseases, mainly due to the presence of unliganded iron, and thereby the increased production of hydroxyl radicals. It is also known that erythrocytes (RBCs) may play an important role during thrombotic events. Therefore the purpose of the current study was to assess whether RBCs had an altered morphology in individuals with hereditary hemochromatosis (HH), as well as some who displayed hyperferritinemia (HF). Using scanning electron microscopy, we also assessed means by which the RBC and fibrin morphology might be normalized. An important objective was to test the hypothesis that the altered RBC morphology was due to the presence of excess unliganded iron by removing it through chelation. Very striking differences were observed, in that the erythrocytes from HH and HF individuals were distorted and had a much greater axial ratio compared to that accompanying the discoid appearance seen in the normal samples. The response to thrombin, and the appearance of a platelet-rich plasma smear, were also markedly different. These differences could largely be reversed by the iron chelator desferal and to some degree by the iron chelator clioquinol, or by the free radical trapping agents salicylate or selenite (that may themselves also be iron chelators). These findings are consistent with the view that the aberrant morphology of the HH and HF erythrocytes is caused, at least in part, by unliganded (‘free’) iron, whether derived directly via raised ferritin levels or otherwise, and that lowering it or affecting the consequences of its action may be of therapeutic benefit. The findings also bear on the question of the extent to which accepting blood donations from HH individuals may be desirable or otherwise. PMID:24416376

Iron chelating active packaging: Influence of competing ions and pH value on effectiveness of soluble and immobilized hydroxamate chelators.

PubMed

Ogiwara, Yoshiko; Roman, Maxine J; Decker, Eric A; Goddard, Julie M

2016-04-01

Many packaged foods utilize synthetic chelators (e.g. ethylenediaminetetraacetic acid, EDTA) to inhibit iron-promoted oxidation or microbial growth which would result in quality loss. To address consumer demands for all natural products, we have previously developed a non-migratory iron chelating active packaging material by covalent immobilization of polyhydroxamate and demonstrated its efficacy in delaying lipid oxidation. Herein, we demonstrate the ability of this hydroxamate-functionalized iron chelating active packaging to retain iron chelating capacity; even in the presence of competing ions common in food. Both immobilized and soluble hydroxamate chelators retained iron chelating capacity in the presence of calcium, magnesium, and sodium competing ions, although at pH 5.0 the presence of calcium reduced immobilized hydroxamate iron chelation. A strong correlation was found between colorimetric and mass spectral analysis of iron chelation by the chelating packaging material. Such chelating active packaging may support reducing additive use in product formulations, while retaining quality and shelf life. Copyright © 2015 Elsevier Ltd. All rights reserved.

Silica nanoparticle-based dual imaging colloidal hybrids: cancer cell imaging and biodistribution

PubMed Central

Lee, Haisung; Sung, Dongkyung; Kim, Jinhoon; Kim, Byung-Tae; Wang, Tuntun; An, Seong Soo A; Seo, Soo-Won; Yi, Dong Kee

2015-01-01

In this study, fluorescent dye-conjugated magnetic resonance (MR) imaging agents were investigated in T mode. Gadolinium-conjugated silica nanoparticles were successfully synthesized for both MR imaging and fluorescence diagnostics. Polyamine and polycarboxyl functional groups were modified chemically on the surface of the silica nanoparticles for efficient conjugation of gadolinium ions. The derived gadolinium-conjugated silica nanoparticles were investigated by zeta potential analysis, transmission electron microscopy, inductively coupled plasma mass spectrometry, and energy dispersive x-ray spectroscopy. MR equipment was used to investigate their use as contrast-enhancing agents in T1 mode under a 9.4 T magnetic field. In addition, we tracked the distribution of the gadolinium-conjugated nanoparticles in both lung cancer cells and organs in mice. PMID:26357472

Satisfaction and adherence in patients with iron overload receiving iron chelation therapy as assessed by a newly developed patient instrument.

PubMed

Rofail, Diana; Abetz, Linda; Viala, Muriel; Gait, Claire; Baladi, Jean-Francois; Payne, Krista

2009-01-01

This study assesses satisfaction with iron chelation therapy (ICT) based on a reliable and valid instrument, and explores the relationship between satisfaction and adherence to ICT. Patients in the USA and UK completed a new "Satisfaction with ICT" (SICT) instrument consisting of 28 items, three pertaining to adherence. Simple and multivariate regression analyses assessed the relationship between satisfaction with different aspects of ICT and adherence. First assessments of the SICT instrument indicate its validity and reliability. Recommended thresholds for internal consistency, convergent validity, discriminant validity, and floor and ceiling effects were met. A number of variables were identified in the simple linear regression analyses as significant predictors of "never thinking about stopping ICT," a proxy for adherence. These significant variables were entered into the multivariate model to assess the combined factor effects, explaining 42% of the total variance of "never thinking about stopping ICT." A significant and positive relationship was demonstrated between "never thinking about stopping ICT" and age (P = 0.04), Perceived Effectiveness of ICT (P = 0.003), low Burden of ICT (P = 0.002), and low Side Effects of ICT (P = 0.01). The SICT is a reliable and valid instrument which will be useful in ICT clinical trials. Furthermore, the administration of ICT by slow subcutaneous infusion negatively impacts on satisfaction with ICT which was shown to be a determinant of adherence. This points to the need for new more convenient and less burdensome oral iron chelators to increase adherence, and ultimately to improve patient outcomes.

A phase 1 dose-escalation study: safety, tolerability, and pharmacokinetics of FBS0701, a novel oral iron chelator for the treatment of transfusional iron overload.

PubMed

Rienhoff, Hugh Young; Viprakasit, Vip; Tay, Lay; Harmatz, Paul; Vichinsky, Elliott; Chirnomas, Deborah; Kwiatkowski, Janet L; Tapper, Amy; Kramer, William; Porter, John B; Neufeld, Ellis J

2011-04-01

There is still a clinical need for a well-tolerated and safe iron chelator for the treatment of transfusional iron overload. We describe the pharmacokinetic properties and safety data after 7 days of dosing of FBS0701, a novel oral, once-daily iron chelator. This phase 1b dose-escalation study to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of FBS0701, a novel oral iron chelator for the treatment of transfusional iron overload, was conducted in 16 adult patients with iron overloaded consequent to transfusions. FBS0701 was given daily for 7 days at doses up to 32 mg/kg and was well tolerated at all dose levels. Pharmacokinetics showed dose-proportionality. The maxium plasma concentration (C(max)) was reached within 60-90 minutes of dosing and the drug was rapidly distributed at the predicted therapeutic doses. The plasma elimination half-life (t(1/2)) was approximately 19 hours. There were no serious adverse events associated with the drug. Conclusions On the basis of these safety and pharmacokinetic data, FBS0701 warrants further clinical evaluation in patients with transfusional iron overload. (Clinicaltrials.gov identifier: NCT01186419).

Deferasirox: a review of its use for chronic iron overload in patients with non-transfusion-dependent thalassaemia.

PubMed

Shirley, Matt; Plosker, Greg L

2014-06-01

Deferasirox (Exjade(®)) is a once-daily orally administered iron chelator which has been approved for use in the treatment of transfusional-dependent chronic iron overload since 2005. Based primarily on the findings of the THALASSA (Assessment of Exjade(®) in Non-Transfusion-Dependent THALASSemiA) trial, the approval for deferasirox has recently been expanded to include the management of chronic iron overload in patients with non-transfusion-dependent thalassaemia (NTDT) syndromes. Despite the lack of regular blood transfusions, NTDT patients can still develop clinically relevant iron overload, primarily due to increased gastrointestinal absorption secondary to ineffective erythropoiesis, and may require chelation therapy. The THALASSA trial, the first placebo-controlled clinical trial of an iron chelator in NTDT patients, demonstrated that deferasirox was effective in reducing liver iron and serum ferritin levels in this population. Deferasirox has an acceptable tolerability profile, with the most common adverse events reported in the THALASSA trial being related to mild to moderate gastrointestinal disorders. Although further long-term studies will be required to clearly demonstrate the clinical benefit of chelation therapy in NTDT patients, deferasirox presents a useful tool in the management of iron overload in this population.

New tris(dopamine) derivative as an iron chelator. Synthesis, solution thermodynamic stability, and antioxidant research.

PubMed

Zhang, Qingchun; Jin, Bo; Shi, Zhaotao; Wang, Xiaofang; Lei, Shan; Tang, Xingyan; Liang, Hua; Liu, Qiangqiang; Gong, Mei; Peng, Rufang

2017-06-01

A new tris(dopamine) derivative, containing three dopamine chelate moieties which were attached to a trimesic acid molecular scaffold, has been prepared and fully characterized by NMR, FTIR and HRMS. The solution thermodynamic stability of the chelator with Fe(III), Mg(II), Zn(II) and Fe(II) ions was investigated. Results demonstrated that the chelator exhibited effective binding ability and improved selectivity to Fe(III) ion. The chelator possessed affinity similar to that of diethylenetriaminepentaacetic acid chelator for Fe(III) ion. The high affinity could be attributed to the favorable geometric arrangement between the chelator and Fe(III) ion coordination preference. The chelator also exhibited high antioxidant activity and nontoxicity to neuron-like rat pheochromocytoma cells. Hence, the chelator could be used as chelating agent for iron overload situations without depleting essential metal ions, such as Mg(II) and Zn(II) ions. Copyright © 2017. Published by Elsevier Inc.

Influence of delayed gadolinium enhanced MRI of cartilage (dGEMRIC) protocol on T2-mapping: is it possible to comprehensively assess knee cartilage composition in one post-contrast MR examination at 3 Tesla?

PubMed

Verschueren, J; van Tiel, J; Reijman, M; Bron, E E; Klein, S; Verhaar, J A N; Bierma-Zeinstra, S M A; Krestin, G P; Wielopolski, P A; Oei, E H G

2017-09-01

To evaluate the possibility of assessing knee cartilage with T2-mapping and delayed gadolinium enhanced magnetic resonance imaging (MRI) of cartilage (dGEMRIC) in one post-contrast MR examination at 3 Tesla (T). T2 mapping was performed in 10 healthy volunteers at baseline; directly after baseline; after 10 min of cycling; and after 90 min delay, and in 16 osteoarthritis patients before and after intravenous administration of a double dose gadolinium dimeglumine contrast agent, reflecting key dGEMRIC protocol elements. Differences in T2 relaxation times between each timepoint and baseline were calculated for 6 cartilage regions using paired t tests or Wilcoxon signed-rank tests and the smallest detectable change (SDC). After cycling, a significant change in T2 relaxation times was found in the lateral weight-bearing tibial plateau (+1.0 ms, P = 0.04). After 90 min delay, significant changes were found in the lateral weight-bearing femoral condyle (+1.2 ms, P = 0.03) and the lateral weight-bearing tibial plateau (+1.3 ms, P = 0.01). In these regions of interests (ROIs), absolute differences were small and lower than the corresponding SDCs. T2-mapping after contrast administration only showed statistically significantly lower T2 relaxation times in the medial posterior femoral condyle (-2.4 ms, P < 0.001) with a change exceeding the SDC. Because dGEMRIC protocol elements resulted in only small differences in T2 relaxation times that were not consistent and lower than the SDC in the majority of regions, our results suggest that T2-mapping and dGEMRIC can be performed reliably in a single imaging session to assess cartilage biochemical composition in knee osteoarthritis (OA) at 3 T. Copyright © 2017 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

A study on the imaging characteristics of Gold nanoparticles as a contrast agent in X-ray computed tomography

NASA Astrophysics Data System (ADS)

Mesbahi, Asghar; Famouri, Fatemeh; Ahar, Mohammad Johari; Ghaffari, Maryam Olade; Ghavami, Seyed Mostafa

2017-03-01

Aim: In the current study, some imaging characteristics of AuNPs were quantitatively analyzed and compared with two conventional contrast media (CM) including Iodine and Gadolinium by using of a cylindrical phantom. Methods: AuNPs were synthesized with the mean diameter of 16 nm and were equalized to the concentration of 0.5, 1, 2 and 4 mg/mL in the same volumes. A cylindrical phantom resembling the head and neck was fabricated and drilled to contain small tubes filled with Iodine, Gadolinium, and AuNPs as contrast media. The phantom was scanned in different exposure techniques and CT numbers of three studied contrast media inside test tubes were measured in terms of Hounsfield Unit (HU). The imaging parameters of the noise and contrast to noise ratios (CNR) were calculated for all studied CMs. Results: AuNPs showed 128% and 166% higher CT number in comparison with Iodine and Gadolinium respectively. Also, Iodine had a greater CT number than Gadolinium for the same exposure techniques and concentration. The maximum CT number for AuNPs and studied contrast materials was obtained at the highest mAs and the lowest tube potential. The maximum CT number were 1033±11 (HU) for AuNP, 565±10 (HU) for Iodine, 458±11 for Gadolinium. Moreover, the maximum CNRs of 433±117, 203±53, 145±37 were found for AuNPs, Iodine and Gadolinium respectively. Conclusion: The contrast agent based on AuNPs showed higher imaging quality in terms of contrast and noise relative to other iodine and gadolinium based contrast media in X-ray computed tomography. Application of the AuNPs as a contrast medium in x-ray CT is recommended.

Polythermal investigation of viscosity of solution of metal carboxylates in VIK-grade mixed carboxylic acids: Yttrium and gadolinium carboxylates

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mezhov, E.A.; Samatov, A.V.; Troyanovskii, L.V.

Kinematic viscosities have been measured for solutions of yttrium and gadolinium carboxylates in grade VIK mixed carboxylic acids (MCA). It has been established that the optimal fluidity of these metal carboxylate solutions for application to articles is reached at 333 K. A regression model has been developed to describe the concentration and temperature dependences of the viscosity of yttrium- and gadolinium-containing MCA solutions. 2 refs., 3 tabs.

Gadolinium deposition disease: Initial description of a disease that has been around for a while.

PubMed

Semelka, Richard C; Ramalho, Joana; Vakharia, Ami; AlObaidy, Mamdoh; Burke, Lauren M; Jay, Michael; Ramalho, Miguel

2016-12-01

To describe the clinical manifestations of presumed gadolinium toxicity in patients with normal renal function. Participants were recruited from two online gadolinium toxicity support groups. The survey was anonymous and individuals were instructed to respond to the survey only if they had evidence of normal renal function, evidence of gadolinium in their system beyond 30days of this MRI, and no pre-existent clinical symptoms and/or signs of this type. 42 subjects responded to the survey (age: 28-69, mean 49.1±22.4years). The most common findings were: central pain (n=15), peripheral pain (n=26), headache (n=28), and bone pain (n=26). Only subjects with distal leg and arm distribution described skin thickening (n=22). Clouded mentation and headache were the symptoms described as persistent beyond 3months in 29 subjects. Residual disease was present in all patients. Twenty-eight patients described symptoms following administration of one brand of Gadolinium-Based Contrast Agent (GBCA), 21 after a single GBCA administration and 7 after multiple GBCA administrations, including: gadopentetate dimeglumine, n=9; gadodiamide, n=4; gadoversetamide, n=4; gadobenate dimeglumine, n=4; gadobutrol, n=1; gadoteridol, n=2; and unknown, n=4. Gadolinium toxicity appears to arise following GBCA administration, which appears to contain clinical features seen in Nephrogenic Systemic Fibrosis, but also features not observed in that condition. Copyright © 2016 Elsevier Inc. All rights reserved.

In vitro study of novel gadolinium-loaded liposomes guided by GBI-10 aptamer for promising tumor targeting and tumor diagnosis by magnetic resonance imaging

PubMed Central

Gu, Meng-Jie; Li, Kun-Feng; Zhang, Lan-Xin; Wang, Huan; Liu, Li-Si; Zheng, Zhuo-Zhao; Han, Nan-Yin; Yang, Zhen-Jun; Fan, Tian-Yuan

2015-01-01

Novel gadolinium-loaded liposomes guided by GBI-10 aptamer were developed and evaluated in vitro to enhance magnetic resonance imaging (MRI) diagnosis of tumor. Nontargeted gadolinium-loaded liposomes were achieved by incorporating amphipathic material, Gd (III) [N,N-bis-stearylamidomethyl-N′-amidomethyl] diethylenetriamine tetraacetic acid, into the liposome membrane using lipid film hydration method. GBI-10, as the targeting ligand, was then conjugated onto the liposome surface to get GBI-10-targeted gadolinium-loaded liposomes (GTLs). Both nontargeted gadolinium-loaded liposomes and GTLs displayed good dispersion stability, optimal size, and zeta potential for tumor targeting, as well as favorable imaging properties with enhanced relaxivity compared with a commercial MRI contrast agent (CA), gadopentetate dimeglumine. The use of GBI-10 aptamer in this liposomal system was intended to result in increased accumulation of gadolinium at the periphery of C6 glioma cells, where the targeting extracellular matrix protein tenascin-C is overexpressed. Increased cellular binding of GTLs to C6 cells was confirmed by confocal microscopy, flow cytometry, and MRI, demonstrating the promise of this novel delivery system as a carrier of MRI contrast agent for the diagnosis of tumor. These studies provide a new strategy furthering the development of nanomedicine for both diagnosis and therapy of tumor. PMID:26316749

Phytochelators Intended for Clinical Use in Iron Overload, Other Diseases of Iron Imbalance and Free Radical Pathology.

PubMed

Kontoghiorghe, Christina N; Kolnagou, Annita; Kontoghiorghes, George J

2015-11-23

Iron chelating drugs are primarily and widely used in the treatment of transfusional iron overload in thalassaemia and similar conditions. Recent in vivo and clinical studies have also shown that chelators, and in particular deferiprone, can be used effectively in many conditions involving free radical damage and pathology including neurodegenerative, renal, hepatic, cardiac conditions and cancer. Many classes of phytochelators (Greek: phyto (φυτό)-plant, chele (χηλή)-claw of the crab) with differing chelating properties, including plant polyphenols resembling chelating drugs, can be developed for clinical use. The phytochelators mimosine and tropolone have been identified to be orally active and effective in animal models for the treatment of iron overload and maltol for the treatment of iron deficiency anaemia. Many critical parameters are required for the development of phytochelators for clinical use including the characterization of the therapeutic targets, ADMET, identification of the therapeutic index and risk/benefit assessment by comparison to existing therapies. Phytochelators can be developed and used as main, alternative or adjuvant therapies including combination therapies with synthetic chelators for synergistic and or complimentary therapeutic effects. The development of phytochelators is a challenging area for the introduction of new pharmaceuticals which can be used in many diseases and also in ageing. The commercial and other considerations for such development have great advantages in comparison to synthetic drugs and could also benefit millions of patients in developing countries.

Diagnostic significance of gadolinium-DTPA (diethylenetriamine penta-acetic acid) enhanced magnetic resonance imaging in thrombolytic treatment for acute myocardial infarction: its potential in assessing reperfusion.

PubMed Central

van der Wall, E E; van Dijkman, P R; de Roos, A; Doornbos, J; van der Laarse, A; Manger Cats, V; van Voorthuisen, A E; Matheijssen, N A; Bruschke, A V

1990-01-01

The diagnostic value of gadolinium-DTPA (diethylenetriamine penta-acetic acid) enhanced magnetic resonance imaging in patients treated by thrombolysis for acute myocardial infarction was assessed in 27 consecutive patients who had a first acute myocardial infarction (14 anterior, 13 inferior) and who underwent thrombolytic treatment and coronary arteriography within 4 hours of the onset of symptoms. Magnetic resonance imaging was performed 93 hours (range 15-241) after the onset of symptoms. A Philips Gyroscan (0.5 T) was used, and spin echo measurements (echo time 30 ms) were made before and 20 minutes after intravenous injection of 0.1 mmol/kg gadolinium-DTPA. In all patients contrast enhancement of the infarcted areas was seen after Gd-DTPA. The signal intensities of the infarcted and normal values were used to calculate the intensity ratios. Mean (SD) intensity ratios after Gd-DTPA were significantly increased (1.15 (0.17) v 1.52 (0.29). Intensity ratios were higher in the 17 patients who underwent magnetic resonance imaging more than 72 hours after the onset of symptoms than in the 10 who underwent magnetic resonance imaging earlier, the difference being significantly greater after administration of Gd-DTPA (1.38 (0.12) v 1.61 (0.34). When patients were classified according to the site and size of the infarcted areas, or to reperfusion (n = 19) versus non-reperfusion (n = 8), the intensity ratios both before and after Gd-DTPA did not show significant differences. Magnetic resonance imaging with Gd-DTPA improved the identification of acutely infarcted areas, but with current techniques did not identify patients in whom thrombolytic treatment was successful. Images PMID:2310640

Role of MRI T2-DRIVE in the assessment of pituitary stalk abnormalities without gadolinium in pituitary diseases.

PubMed

Godano, Elisabetta; Morana, Giovanni; Di Iorgi, Natascia; Pistorio, Angela; Allegri, Anna Elsa Maria; Napoli, Flavia; Gastaldi, Roberto; Calcagno, Annalisa; Patti, Giuseppa; Gallizia, Annalisa; Notarnicola, Sara; Giaccardi, Marta; Noli, Serena; Severino, Mariasavina; Tortora, Domenico; Rossi, Andrea; Maghnie, Mohamad

2018-06-01

To investigate the role of T2-DRIVE MRI sequence in the accurate measurement of pituitary stalk (PS) size and the identification of PS abnormalities in patients with hypothalamic-pituitary disorders without the use of gadolinium. This was a retrospective study conducted on 242 patients who underwent MRI due to pituitary dysfunction between 2006 and 2015. Among 135 eligible patients, 102 showed eutopic posterior pituitary (PP) gland and 33 showed 'ectopic' PP (EPP). Two readers independently measured the size of PS in patients with eutopic PP at the proximal, midpoint and distal levels on pre- and post-contrast T1-weighted as well as T2-DRIVE images; PS visibility was assessed on pre-contrast T1 and T2-DRIVE sequences in those with EPP. The length, height, width and volume of the anterior pituitary (AP), PP height and length and PP area were analyzed. Significant agreement between the two readers was obtained for T2-DRIVE PS measurements in patients with 'eutopic' PP; a significant difference was demonstrated between the intraclass correlation coefficient calculated on the T2-DRIVE and the T1-pre- and post-contrast sequences. The percentage of PS identified by T2-DRIVE in EPP patients was 72.7% compared to 30.3% of T1 pre-contrast sequences. A significant association was found between the visibility of PS on T2-DRIVE and the height of AP. T2-DRIVE sequence is extremely precise and reliable for the evaluation of PS size and the recognition of PS abnormalities; the use of gadolinium-based contrast media does not add significant information and may thus be avoided. © 2018 European Society of Endocrinology.

Gadolinium-enhanced MR images of the growing piglet skeleton: ionic versus nonionic contrast agent.

PubMed

Menezes, Nina M; Olear, Elizabeth A; Li, Xiaoming; Connolly, Susan A; Zurakowski, David; Foley, Mary; Shapiro, Frederic; Jaramillo, Diego

2006-05-01

To determine whether there are differences in the distribution of ionic and nonionic gadolinium-based contrast agents by evaluating contrast enhancement of the physis, epiphyseal cartilage, secondary ossification center, and metaphysis in the knees of normal piglets. Following approval from the Subcommittee on Research Animal Care, knees of 12 3-week-old piglets were imaged at 3-T magnetic resonance (MR) imaging after intravenous injection of gadoteridol (nonionic contrast agent; n = 6) or gadopentetate dimeglumine (ionic contrast agent; n = 6). Early enhancement evaluation with gradient-echo MR imaging was quantified and compared (Student t test) by means of enhancement ratios. Distribution of contrast material was assessed and compared (Student t test) by means of T1 measurements obtained before and at three 15-minute intervals after contrast agent administration. The relative visibility of the physis, epiphyseal cartilage, secondary ossification center, and metaphysis was qualitatively assessed by two observers and compared (Wilcoxon signed rank test). Differences in matrix content and cellularity that might explain the imaging findings were studied at histologic evaluation. Enhancement ratios were significantly higher for gadoteridol than for gadopentetate dimeglumine in the physis, epiphyseal cartilage, and secondary ossification center (P < .05). After contrast agent administration, T1 values decreased sharply for both agents-but more so for gadoteridol. Additionally, there was less variability in T1 values across structures with this contrast agent. Gadoteridol resulted in greater visibility of the physis, while gadopentetate dimeglumine resulted in greater contrast between the physis and metaphysis (P < .05). The results suggest different roles for the two gadolinium-based contrast agents: The nonionic contrast medium is better suited for evaluating perfusion and anatomic definition in the immature skeleton, while the ionic contrast medium is better for evaluating cartilage fixed-charge density. (c) RSNA, 2006.

Removal of gadolinium, a neutron poison from the moderator system of nuclear reactors.

PubMed

Rufus, A L; Kumar, Padma S; Jeena, K; Velmurugan, S

2018-01-15

Gadolinium as gadolinium nitrate is used as neutron poison in the moderator system for regulating and controlling the power generation of Pressurized Heavy Water Reactors (PHWR) and proposed to be used in Advanced Heavy Water Reactors (AHWR) owing to its high neutron absorption cross section. Removal of the added gadolinium nitrate (Gd 3+ and NO 3 - ) from the system after its intended use is done using ion exchange resins. In the present investigation, attempts have been made to optimize the ion exchange process for generation of low radioactive waste and maximize utilization of the ion exchange resins by employing different types of resins and different modes of operation. The investigations revealed that use of mixed bed (MB) resin column consisting of Strong Acid Cation (SAC) resin and Strong Base Anion (SBA) resin followed by SAC resin column is efficient in removing the Gd 3+ and NO 3 - from the system besides maintaining the pH of the moderator system in the desirable regime, where gadolinium does not get precipitated as its hydroxide. Copyright © 2017 Elsevier B.V. All rights reserved.

Evaluation of copper toxicity using site specific algae and water chemistry: Field validation of laboratory bioassays.

PubMed

Fawaz, Elyssa G; Salam, Darine A; Kamareddine, Lina

2018-07-15

Studies of metal toxicity to microalgae have predominantly been conducted using single non-target algae species and without due regard for the chemistry of the treated waters, leading to ineffective or excessive algaecide treatments. In this study, indigenous multi-algal species (Scenedesmus quadricauda, and Scenedesmus subspicatus and Oscillatoria agardhii) were used in laboratory toxicity bioassays under simulated field water chemistry (pH = 7.2, hardness = 196 mg L -1 as CaCO 3 , and alkalinity = 222 mg L -1 as CaCO 3 ) to determine the optimum copper sulfate treatment dose to control algae growth in an irrigation canal. Toxicity bioassays were conducted using copper sulfate in chelated (with EDTA) and non-chelated (without EDTA) forms to assess the influence of the use of synthetic chelators in toxicity studies. Also, copper toxicity to the indigenous algae species was measured in the non-modified EPA test medium (pH = 7.5, hardness = 92 mg L -1 as CaCO 3 , alkalinity = 10 mg L -1 as CaCO 3 and EDTA= 300 µg L -1 ) to assess the impact of the water chemistry on algae inhibitory algal dosages. Under simulated water chemistry conditions, lower toxicity was measured in the test flasks with the chelated form of copper (96 h- EC 50 = 386.67 µg L -1 as Cu) as compared to those with the non-chelated metal (96 h-EC 50 = 217.17 µg L -1 as Cu). In addition, higher copper toxicity was measured in the test flasks prepared with the non-modified EPA medium using chelated copper (96 h-EC 50 = 65.93 µg L -1 as Cu) as compared to their analogous microcosms with modified water chemistry (96 h-EC 50 = 386.67 µg L -1 as Cu), the increased water hardness and alkalinity in the latter case contributing to the decrease of the metal bioavailability. Results from laboratory experiments showed good correlation with copper dosages used in a small scale field testing to control algae growth, increasing confidence in laboratory bioassays. Copyright © 2018 Elsevier Inc. All rights reserved.

Method of encapsulating polyaminopolycarboxylic acid chelating agents in liposomes

DOEpatents

Rahman, Yueh Erh

1977-11-10

A method is provided for transferring a polyaminopolycarboxylic acid chelating agent across a cellular membrane by encapsulating the charged chelating agent within liposomes, which liposomes will be taken up by the cells, thereby transferring the chelating agent across the cellular membrane. The chelating agent is encapsulated within liposomes by drying a lipid mixture to form a thin film and wetting the lipid film with a solution containing the chelating agent. Mixing then results in the formation of a suspension of liposomes encapsulating the chelating agent, which liposomes can then be separated.

Non-Invasive Methods for Iron Concentration Assessment

NASA Astrophysics Data System (ADS)

Carneiro, Antonio A. O.; Baffa, Oswaldo; Angulo, Ivan L.; Covas, Dimas T.

2002-08-01

Iron excess is commonly observed in patients with transfusional iron overload. The iron chelation therapy in these patients require accurate determination of the magnitude of iron excess. The most promising method for noninvasive assessment of iron stores is based on measurements of hepatic magnetic susceptibility.

Influence of magnetization on the applied magnetic field in various AMR regenerators

NASA Astrophysics Data System (ADS)

Mira, A.; de Larochelambert, T.; Espanet, C.; Giurgea, S.; Nika, P.; Bahl, C. R. H.; Bjørk, R.; Nielsen, K. K.

2017-10-01

The aim of this work is to assess the influence of a magnetic sample on the applied magnetic field inside the air gap of a magnetic circuit. Different magnetic sources including an electromagnet, a permanent magnet in a soft ferromagnetic toroidal yoke, as well as 2D and 3D Halbach cylinders are considered, using a numerical model. Gadolinium is chosen as magnetic material for the sample, due to its strong magnetocaloric properties and its wide use in magnetic refrigeration prototypes. We find that using uniform theoretical demagnetizing factors for cylinders or spheres results in a deviation of less than 2% in the calculation of internal magnetic fields at temperatures above the Curie point of gadolinium. Below the Curie point, a stronger magnetization of the cylinders and spheres leads to a larger deviation which can reach 8% when using uniform demagnetizing factors for internal magnetic field calculations.

Gadolinium-Conjugated Gold Nanoshells for Multimodal Diagnostic Imaging and Photothermal Cancer Therapy

PubMed Central

Coughlin, Andrew J.; Ananta, Jeyarama S.; Deng, Nanfu; Larina, Irina V.; Decuzzi, Paolo

2014-01-01

Multimodal imaging offers the potential to improve diagnosis and enhance the specificity of photothermal cancer therapy. Toward this goal, we have engineered gadolinium-conjugated gold nanoshells and demonstrated that they enhance contrast for magnetic resonance imaging, X-Ray, optical coherence tomography, reflectance confocal microscopy, and two-photon luminescence. Additionally, these particles effectively convert near-infrared light to heat, which can be used to ablate cancer cells. Ultimately, these studies demonstrate the potential of gadolinium-nanoshells for image-guided photothermal ablation. PMID:24115690

Gadolinium Scandium Gallium Garnet (GSGG) as a Solid-State Laser Host

DTIC Science & Technology

1987-07-01

o*SATI CODSi1.SBEC EM (otne nrvrs fnceayad dniy nb)k ubr ~~~~~~~~ Gadolinium Scandium Gallium Garnet (GSGG)asaSldtteLerHt 17. ABSTRACT 6.SUJCTTEM...certain other garnet materials for replacement. It also addresses the solid-state laser host material Gadolinium Scandium Gal- lium Garnet (GSGG) and its...by neodymium-doped yttrium aluminum garnet (Nd:YAG) or other mate- rials for most applications. In the years after the invention of the ruby laser, in

Method for preparing radionuclide-labeled chelating agent-ligand complexes

DOEpatents

Meares, Claude F.; Li, Min; DeNardo, Sally J.

1999-01-01

Radionuclide-labeled chelating agent-ligand complexes that are useful in medical diagnosis or therapy are prepared by reacting a radionuclide, such as .sup.90 Y or .sup.111 In, with a polyfunctional chelating agent to form a radionuclide chelate that is electrically neutral; purifying the chelate by anion exchange chromatography; and reacting the purified chelate with a targeting molecule, such as a monoclonal antibody, to form the complex.

Concepts and goals in the management of transfusional iron overload.

PubMed

Porter, John B

2007-12-01

In this review, current concepts and goals of iron chelation therapy for thalassemias, sickle cell disease, and myelodysplastic syndromes are discussed. The primary goal of iron chelation therapy is to prevent the accumulation of iron reaching harmful levels by matching iron intake from blood transfusion, with iron excreted by iron chelation. Over 30 years of experience with deferoxamine has shown iron chelation to be an effective therapeutic modality. However, chelation efficiency is limited because most of the body's iron stores are not directly chelatable, and only a small fraction of body iron is chelatable at any moment. Once iron has been deposited in organs other than the liver, for example the heart, removal by chelation is slow and inefficient. Chelation efficiency can be improved by designing regimes where chelators are available 24 hr a day to bind labile iron pools in cells and plasma. Deferoxamine has a short plasma half-life and the parenteral infusions required to achieve steady plasma levels are demanding, with consequent variable adherence to therapy. Once-daily oral administration of deferasirox achieves continuous chelation with trough concentrations sufficient to decrease plasma labile iron species progressively, and achieves an efficiency of chelation not obtainable with deferiprone or deferoxamine monotherapy. 2007 Wiley-Liss, Inc

Heavy metal staining, a comparative assessment of gadolinium chloride and osmium tetroxide for inner ear labyrinthine contrast enhancement using X-ray microtomography.

PubMed

Wong, Christopher C; Curthoys, Ian S; O'Leary, Stephen J; Jones, Allan S

2013-01-01

The use of both gadolinium chloride (GdCl(3)) and osmium tetroxide (OsO(4)) allowed for the visualization of the membranous labyrinth and other intralabyrinthine structures, at different intensities, as compared with the control sample. This initial comparison shows the advantages of GdCl(3) in radiological assessments and OsO(4) in more detailed anatomical studies and pathways of labyrinthine pathogenesis using X-ray microtomography (microCT). To assess an improved OsO(4) staining protocol and compare the staining affinities against GdCl(3). Guinea pig temporal bones were stained with either GdCl(3) (2% w/v) for 7 days or OsO(4) (2% w/v) for 3 days, and scanned in a microCT system. The post-scanned datasets were then assessed in a 3D rendering program. The enhanced soft tissue contrast as presented in the temporal bones stained with either GdCl(3) or OsO(4) allowed for the membranous labyrinth to be visualized throughout the whole specimen. GdCl(3)-stained specimens presented more defined contours of the bone profile in the radiographs, while OsO(4)-stained specimens provided more anatomical detail of individual intralabyrinthine structures, hence allowing spatial relationships to be visualized with ease in a 3D rendering context and 2D axial slice images.

Chelating agents.

PubMed

Bergan, T; Klaveness, J; Aasen, A J

2001-01-01

The antibacterial activity of metal ions, metal chelates, and molecules with chelating ability for polyvalent cations have been evaluated. The chelator N, N'-ethylenebis[2-(2-hydroxyphenyl)-glycine] (EHPG) exerted moderate-to-good activity against isolates of pathogenic bacteria and fungi. Other chelating agents such as ethylenediamine-tetraacetic acid (EDTA) and diethylene-triamine-pentaacetic acid (DTPA) revealed weak-to-moderate activity. Metal chelation of ligands reduced the activity of EDTA and DTPA. Copyright 2001 S. Karger AG, Basel

Method and apparatus for back-extracting metal chelates

DOEpatents

Wai, Chien M.; Smart, Neil G.; Lin, Yuehe

1998-01-01

A method of extracting metal and metalloid species from a solid or liquid substrate using a supercritical fluid solvent containing one or more chelating agents followed by back-extracting the metal and metalloid species from the metal and metalloid chelates formed thereby. The back-extraction acidic solution is performed utilizing an acidic solution. Upon sufficient exposure of the metal and metalloid chelates to the acidic solution, the metal and metalloid species are released from the chelates into the acid solution, while the chelating agent remains in the supercritical fluid solvent. The chelating agent is thereby regenerated and the metal and metalloid species recovered.

Novel hexadentate and pentadentate chelators for 64Cu-based targeted PET imaging

PubMed Central

Sin, Inseok; Kang, Chisoo; Bandara, Nilantha; Sun, Xiang; Zhong, Yongliang; Rogers, Buck E.; Chong, Hyun-Soon

2014-01-01

A series of new hexadentate and pentadentate chelators were designed and synthesized as chelators of 64Cu. The new pentadentate and hexadentate chelators contain different types of donor groups and are expected to form neutral complexes with Cu(II). The new chelators were evaluated for complex kinetics and stability with 64Cu. The new chelators instantly bound to 64Cu with high labeling efficiency and maximum specific activity. All 64Cu-radiolabeled complexes in human serum remained intact for 2 days. The 64Cu-radiolabeled complexes were further challenged by EDTA in a 100-fold molar excess. Among the 64Cu-radiolabeled complexes evaluated, 64Cu-complex of the new chelator E was well tolerated with a minimal transfer of 64Cu to EDTA. 64Cu-radiolabeled complex of the new chelator E was further evaluated for biodistribution studies using mice and displayed rapid blood clearance and low organ uptake. 64Cu-chelator E produced a favorable in vitro and in vivo complex stability profiles comparable to 64Cu complex of the known hexadentate NOTA chelator. The in vitro and in vivo data highlight strong potential of the new chelator E for targeted PET imaging application. PMID:24657050

Gadolinium photoionization process

DOEpatents

Paisner, J.A.; Comaskey, B.J.; Haynam, C.A.; Eggert, J.H.

1993-04-13

A method is provided for selective photoionization of the odd-numbered atomic mass gadolinium isotopes 155 and 157. The selective photoionization is accomplished by circular or linear parallel polarized laser beam energy effecting a three-step photoionization pathway.

Gadolinium photoionization process

DOEpatents

Paisner, Jeffrey A.; Comaskey, Brian J.; Haynam, Christopher A.; Eggert, Jon H.

1993-01-01

A method is provided for selective photoionization of the odd-numbered atomic mass gadolinium isotopes 155 and 157. The selective photoionization is accomplished by circular or linear parallel polarized laser beam energy effecting a three-step photoionization pathway.

Kinetic characteristics of the luminescence decay for industrial yttrium-gadolinium-aluminium garnet based phosphors

NASA Astrophysics Data System (ADS)

Lisitsyn, V. M.; Stepanov, S. A.; Valiev, D. T.; Vishnyakova, E. A.; Abdullin, H. A.; Marhabaeva, A. A.; Tulegenova, A. T.

2016-02-01

The spectral and decay kinetic characteristics of pulse cathodoluminescence and photoluminescence of phosphors based on yttrium-gadolinium-aluminum garnet were investigated using pulsed optical time resolved spectroscopy.

Transient arterial phase respiratory motion-related artifact in MR imaging of the liver: an analysis of four different gadolinium-based contrast agents.

PubMed

Shah, Mansi R; Flusberg, Milana; Paroder, Viktoriya; Rozenblit, Alla M; Chernyak, Victoria

The purpose was to compare hepatic arterial phase (HAP) respiratory motion artifact (RMA) between gadoxetate, gadobutrol, gadopentetate, and gadobenate. Two hundred cases of each gadolinium agent were included. RMA was assigned using 5-point Likert scale (1=no motion, 5=extreme motion) on precontrast and HAP. RMA increase (increase ≥1 on HAP from precontrast) was the outcome in logistic regression. Odds of RMA increase for gadoxetate were 5.5 (P<.001), 3.6 (P=.034), and 9.5 (P<.001) times higher than gadobutrol, gadopentetate, and gadobenate, respectively. Gadolinium volume and dose were not independent predictors of RMA increase. Gadoxetate has increased odds of RMA compared with other gadolinium agents; tight contrast bolus is not a contributor. Copyright © 2016 Elsevier Inc. All rights reserved.

The High Radiosensitizing Efficiency of a Trace of Gadolinium-Based Nanoparticles in Tumors

NASA Astrophysics Data System (ADS)

Dufort, Sandrine; Le Duc, Géraldine; Salomé, Murielle; Bentivegna, Valerie; Sancey, Lucie; Bräuer-Krisch, Elke; Requardt, Herwig; Lux, François; Coll, Jean-Luc; Perriat, Pascal; Roux, Stéphane; Tillement, Olivier

2016-07-01

We recently developed the synthesis of ultrasmall gadolinium-based nanoparticles (GBN), (hydrodynamic diameter <5 nm) characterized by a safe behavior after intravenous injection (renal clearance, preferential accumulation in tumors). Owing to the presence of gadolinium ions, GBN can be used as contrast agents for magnetic resonance imaging (MRI) and as radiosensitizers. The attempt to determine the most opportune delay between the intravenous injection of GBN and the irradiation showed that a very low content of radiosensitizing nanoparticles in the tumor area is sufficient (0.1 μg/g of particles, i.e. 15 ppb of gadolinium) for an important increase of the therapeutic effect of irradiation. Such a promising and unexpected result is assigned to a suited distribution of GBN within the tumor, as revealed by the X-ray fluorescence (XRF) maps.

Characterization of the reaction products and precipitates at the interface of carbon fiber reinforced magnesium–gadolinium composite

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Yaping; Jiang, Longtao, E-mail: longtaojiang@163.com; Chen, Guoqin

2016-03-15

In the present work, carbon fiber reinforced magnesium-gadolinium composite was fabricated by pressure infiltration method. The phase composition, micro-morphology, and crystal structure of reaction products and precipitates at the interface of the composite were investigated. Scanning electron microscopy and energy dispersive spectroscopy analysis revealed the segregation of gadolinium element at the interface between carbon fiber and matrix alloy. It was shown that block-shaped Gd4C5, GdC2 and nano-sized Gd2O3 were formed at the interface during the fabrication process due to the interfacial reaction. Furthermore, magnesium-gadolinium precipitates including needle-like Mg5Gd (or Mg24Gd5) and thin plate-shaped long period stacking-ordered phase, were also observedmore » at the interface and in the matrix near the interface. The interfacial microstructure and bonding mode were influenced by these interfacial products, which were beneficial for the improvement of the interfacial bonding strength. - Highlights: • Gadolinium element segregated on the surface of carbon fibers. • Block-shaped Gd{sub 4}C{sub 5} and GdC{sub 2} were formed at the interface via chemical reaction. • Gadolinium and oxygen reacted at the interface and formed nano-scaled Gd{sub 2}O{sub 3}. • The precipitates formed in the interface were identified to be Mg{sub 5}Gd (or Mg{sub 24}Gd{sub 5}) and plate-shaped long period stacking-ordered phase.« less

Carboxylate-containing chelating agent interactions with amorphous chromium hydroxide: Adsorption and dissolution

NASA Astrophysics Data System (ADS)

Carbonaro, Richard F.; Gray, Benjamin N.; Whitehead, Charles F.; Stone, Alan T.

2008-07-01

Anthropogenic chelating agents and biological chelating agents produced by indigenous organisms may dissolve Cr III (hydr)oxides in soils and sediments. The resulting dissolved Cr III-chelating agent complexes are more readily transported through porous media, thereby spreading contamination. With this work, we examine chelating agent-assisted dissolution of amorphous chromium hydroxide (ACH) by the (amino)carboxylate chelating agents iminodiacetic acid (IDA), nitrilotriacetic acid (NTA), tricarballylic acid (TCA), citric acid (CIT), ethylenediaminetetraacetic acid (EDTA), trans-1,2-cyclohexanediaminetetraacetic acid (CDTA), and trimethylenediaminetetraacetic acid (TMDTA). The extent of chelating agent adsorption onto ACH increased quickly over the first few hours, and then increased more gradually until a constant extent was attained. The extent of chelating agent adsorption versus pH followed "ligand-like" behavior. All chelating agents with the exception of TCA and IDA effectively dissolved significant amounts of ACH within 10 days from pH 4.0 to 9.4. IDA dissolved ACH below pH 6.5 and above pH 7.5. Rates of ACH dissolution normalized to the extent of chelating agent adsorption were pH dependent. IDA, NTA, CIT, and CDTA exhibited an increase in normalized dissolution rate with decreasing pH. EDTA and TMDTA exhibited a maximum in normalized dissolution rate near pH 8.5. Use of acetic acid as a pH buffer in experiments decreased the extent of chelating agent adsorption for IDA, NTA, and CIT but increased normalized rates of chelating agent-assisted dissolution for all chelating agents except EDTA. The results from this study provide the necessary information to calculate the extents and time scales of ACH dissolution in the presence of (amino)carboxylate chelating agents.

Method and apparatus for back-extracting metal chelates

DOEpatents

Wai, C.M.; Smart, N.G.; Lin, Y.

1998-08-11

A method is described for extracting metal and metalloid species from a solid or liquid substrate using a supercritical fluid solvent containing one or more chelating agents followed by back-extracting the metal and metalloid species from the metal and metalloid chelates formed thereby. The back-extraction acidic solution is performed utilizing an acidic solution. Upon sufficient exposure of the metal and metalloid chelates to the acidic solution, the metal and metalloid species are released from the chelates into the acid solution, while the chelating agent remains in the supercritical fluid solvent. The chelating agent is thereby regenerated and the metal and metalloid species recovered. 3 figs.

Porphyrin-containing polyaspartamide gadolinium complexes as potential magnetic resonance imaging contrast agents.

PubMed

Yan, Guo-Ping; Li, Zhen; Xu, Wei; Zhou, Cheng-Kai; Yang, Lian; Zhang, Qiao; Li, Liang; Liu, Fan; Han, Lin; Ge, Yuan-Xing; Guo, Jun-Fang

2011-04-04

Porphyrin-containing polyaspartamide ligands (APTSPP-PHEA-DTPA) were synthesized by the incorporation of diethylenetriaminepentaacetic acid (DTPA) and 5-(4'-aminophenyl)-10,15,20-tris(4'-sulfonatophenyl) porphyrin, trisodium salt (APTSPP) into poly-α,β-[N-(2-hydroxyethyl)-l-aspartamide] (PHEA). These ligands were further reacted with gadolinium chloride to produce macromolecule-gadolinium complexes (APTSPP-PHEA-DTPA-Gd). Experimental data of (1)H NMR, IR, UV and elemental analysis evidenced the formation of the polyaspartamide ligands and gadolinium complexes. In vitro and in vivo property tests indicated that APTSPP-PHEA-DTPA-Gd possessed noticeably higher relaxation effectiveness, less toxicity to HeLa cells, and significantly higher enhanced signal intensities (SI) of the VX2 carcinoma in rabbits with lower injection dose requirement than that of Gd-DTPA. Moreover, APTSPP-PHEA-DTPA-Gd was found to greatly enhance the contrast of MR images of the VX2 carcinoma, providing prolonged intravascular duration, and distinguished the VX2 carcinoma and normal tissues in rabbits according to MR image signal enhancements. These porphyrin-containing polyaspartamide gadolinium complexes can be used as the candidates of contrast agents for targeted MRI to tumors. Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.

Solid solutions of gadolinium doped zinc oxide nanorods by combined microwave-ultrasonic irradiation assisted crystallization

NASA Astrophysics Data System (ADS)

Kiani, Armin; Dastafkan, Kamran; Obeydavi, Ali; Rahimi, Mohammad

2017-12-01

Nanocrystalline solid solutions consisting of un-doped and gadolinium doped zinc oxide nanorods were fabricated by a modified sol-gel process utilizing combined ultrasonic-microwave irradiations. Polyvinylpyrrolidone, diethylene glycol, and triethylenetetramine respectively as capping, structure directing, and complexing agents were used under ultrasound dynamic aging and microwave heating to obtain crystalline nanorods. Crystalline phase monitoring, lattice parameters and variation, morphology and shape, elemental analysis, functional groups, reducibility, and the oxidation state of emerged species were examined by PXRD, FESEM, TEM, EDX, FTIR, micro Raman, H2-TPR, and EPR techniques. Results have verified that irradiation mechanism of gelation and crystallization reduces the reaction time, augments the crystal quality, and formation of hexagonal close pack structure of Wurtzite morphology. Besides, dissolution of gadolinium within host lattice involves lattice deformation, unit cell distortion, and angular position variation. Structure related shape and growth along with compositional purity were observed through microscopic and spectroscopic surveys. Furthermore, TPR and EPR studies elucidated more detailed behavior upon exposure to the exerted irradiations and subsequent air-annealing including the formed oxidation states and electron trapping centers, presence of gadolinium, zinc, and oxygen disarrays and defects, as well as alteration in the host unit cell via gadolinium addition.

Brain iron chelation by deferiprone in a phase 2 randomised double-blinded placebo controlled clinical trial in Parkinson's disease.

PubMed

Martin-Bastida, Antonio; Ward, Roberta J; Newbould, Rexford; Piccini, Paola; Sharp, David; Kabba, Christina; Patel, Maneesh C; Spino, Michael; Connelly, John; Tricta, Fernando; Crichton, Robert R; Dexter, David T

2017-05-03

Parkinson's disease (PD) is associated with increased iron levels in the substantia nigra (SNc). This study evaluated whether the iron chelator, deferiprone, is well tolerated, able to chelate iron from various brain regions and improve PD symptomology. In a randomised double-blind, placebo controlled trial, 22 early onset PD patients, were administered deferiprone, 10 or 15 mg/kg BID or placebo, for 6 months. Patients were evaluated for PD severity, cognitive function, depression rating and quality of life. Iron concentrations were assessed in the substantia nigra (SNc), dentate and caudate nucleus, red nucleus, putamen and globus pallidus by T2* MRI at baseline and after 3 and 6 months of treatment. Deferiprone therapy was well tolerated and was associated with a reduced dentate and caudate nucleus iron content compared to placebo. Reductions in iron content of the SNc occurred in only 3 patients, with no changes being detected in the putamen or globus pallidus. Although 30 mg/kg deferiprone treated patients showed a trend for improvement in motor-UPDRS scores and quality of life, this did not reach significance. Cognitive function and mood were not adversely affected by deferiprone therapy. Such data supports more extensive clinical trials into the potential benefits of iron chelation in PD.

Antibacterial and antibiofilm effects of iron chelators against Prevotella intermedia.

PubMed

Moon, Ji-Hoi; Kim, Cheul; Lee, Hee-Su; Kim, Sung-Woon; Lee, Jin-Yong

2013-09-01

Prevotella intermedia, a major periodontopathogen, has been shown to be resistant to many antibiotics. In the present study, we examined the effect of the FDA-approved iron chelators deferoxamine (DFO) and deferasirox (DFRA) against planktonic and biofilm cells of P. intermedia in order to evaluate the possibility of using these iron chelators as alternative control agents against P. intermedia. DFRA showed strong antimicrobial activity (MIC and MBC values of 0.16 mg ml(-1)) against planktonic P. intermedia. At subMICs, DFRA partially inhibited the bacterial growth and considerably prolonged the bacterial doubling time. DFO was unable to completely inhibit the bacterial growth in the concentration range tested and was not bactericidal. Crystal violet binding assay for the assessment of biofilm formation by P. intermedia showed that DFRA significantly decreased the biofilm-forming activity as well as the biofilm formation, while DFO was less effective. DFRA was chosen for further study. In the ATP-bioluminescent assay, which reflects viable cell counts, subMICs of DFRA significantly decreased the bioactivity of biofilms in a concentration-dependent manner. Under the scanning electron microscope, P. intermedia cells in DFRA-treated biofilm were significantly elongated compared to those in untreated biofilm. Further experiments are necessary to show that iron chelators may be used as a therapeutic agent for periodontal disease.

Hydroxypyridonate chelating agents and synthesis thereof

DOEpatents

Raymond, K.N.; Scarrow, R.C.; White, D.L.

1985-11-12

Chelating agents having 1-hydroxy-2-pyridinone (HOPO) and related moieties incorporated within their structures, including polydentate HOPO-substituted polyamines such as spermidine and spermine, and HOPO-substituted desferrioxamine. The chelating agents are useful in selectively removing certain cations from solution, and are particularly useful as ferric ion and actinide chelators. Novel syntheses of the chelating agents are provided. 4 tabs.

Magnetization reversal and inverted magnetoresistance of exchange-biased spin valves with a gadolinium layer

NASA Astrophysics Data System (ADS)

Milyaev, M.; Naumova, L.; Chernyshova, T.; Proglyado, V.; Kamensky, I.; Krinitsina, T.; Ryabukhina, M.; Ustinov, V.

2017-03-01

FeMn-based spin valves with a gadolinium layer have been fabricated by magnetron sputtering. The magnetoresistive properties of the spin valves have been investigated at temperatures of 80-293 K. Temperature-induced switching between low- and high-resistance magnetic states has been revealed. Realization of the low- or high-resistance states depends on which magnetic moment dominates in the exchange-coupled Gd/CoFe, of Gd or CoFe. It has been shown that the switching temperature depends on the thickness of the gadolinium layer.

A natural antioxidant, tannic acid mitigates iron-overload induced hepatotoxicity in Swiss albino mice through ROS regulation.

PubMed

Basu, Tapasree; Panja, Sourav; Shendge, Anil Khushalrao; Das, Abhishek; Mandal, Nripendranath

2018-05-01

Tannic acid (TA), a water soluble natural polyphenol with 8 gallic acids groups, is abundantly present in various medicinal plants. Previously TA has been investigated for its antimicrobial and antifungal properties. Being a large polyphenol, TA chelates more than 1 metal. Hence TA has been explored for potent antioxidant activities against reactive oxygen species (ROS), reactive nitrogen species (RNS) and as iron chelator in vitro thereby mitigating iron-overload induced hepatotoxicity in vivo. Iron dextran was injected intraperitoneally in Swiss albino mice to induce iron-overload triggered hepatotoxicity, followed by oral administration of TA for remediation. After treatment, liver, spleen, and blood samples were processed from sacrificed animals. The liver iron, serum ferritin, serum markers, ROS, liver antioxidant status, and liver damage parameters were assessed, followed by histopathology and protein expression studies. Our results show that TA is a prominent ROS and RNS scavenger as well as iron chelator in vitro. It also reversed the ROS levels in vivo and restricted the liver damage parameters as compared to the standard drug, desirox. Moreover, this natural polyphenol exclusively ameliorates the histopathological and fibrotic changes in liver sections reducing the iron-overload, along with chelation of liver iron and normalization of serum ferritin. The protective role of TA against iron-overload induced apoptosis in liver was further supported by changed levels of caspase 3, PARP as well as Bax/BCl-2 ratio. Thus, TA can be envisaged as a better orally administrable iron chelator to reduce iron-overload induced hepatotoxicity through ROS regulation. © 2018 Wiley Periodicals, Inc.

Safety Profile of Oral Iron Chelator Deferiprone in Chinese Children with Transfusion-Dependent Thalassaemia.

PubMed

Botzenhardt, Sebastian; Sing, Chor W; Wong, Ian C K; Chan, Godfrey Chi-Fung; Wong, Lisa Y L; Felisi, Mariagrazia; Rascher, Wolfgang; Ceci, Adriana; Neubert, Antje

2016-01-01

There is a lack of knowledge regarding the incidence of serious adverse drug reactions (ADR) to the oral iron chelator deferiprone in Chinese children with transfusion-dependent thalassaemia. In this retrospective population-based cohort study, paediatric thalassaemia patients in Hong Kong were screened for serious and medically important adverse events related to deferiprone therapy using diagnosis codes, laboratory data and hospital admissions. Potential ADRs were assessed by reviewing concomitant medications, diagnoses and laboratory data and evaluated using standardised causality assessment. Eighty-seven patients contributing 169.8 person-years were included. Thirty ADRs were identified in 21 patients. Most ADRs (56.0%) occurred in the first three months of therapy. Neutropenia occurred in 11 patients (12.6%; incidence rate 6.5 per 100 patient-years) and severe neutropenia (agranulocytosis) was observed in 5 patients (5.7%, incidence rate 2.9 per 100 patient-years). Other identified ADRs involve severe arthropathy, elevated liver enzymes and mild thrombocytopenia. In conclusion, the safety profile of DFP therapy in Chinese children suffering from transfusion-dependent thalassaemia is in line with previous studies of non-Chinese children. However, unlike previous studies, we observed a relatively high incidence of agranulocytosis and neutropenia in patients with simultaneous combined therapy. Hence close monitoring for white blood cell counts is advised in Chinese children under combined iron chelation therapy. Further prospective clinical and pharmacogenetic studies are required to better evaluate this important safety signal. • Half of the identified ADRs related to deferiprone therapy occurred during the first three months of treatment. • A relatively high incidence of agranulocytosis and neutropenia. Hence close monitoring for white blood cell counts is advised in Chinese children under combined iron chelation therapy.

Assessment of a gel-type chelating preparation containing 1-hydroxyethylidene-1, 1-bisphosphonate.

PubMed

Girard, S; Paqué, F; Badertscher, M; Sener, B; Zehnder, M

2005-11-01

To test an aqueous gel containing 1-hydroxyethylidene-1, 1-bisphosphonate (HEBP) regarding its interactions with sodium hypochlorite, its calcium binding capacity, and its potential in preventing the formation of a smear layer when used in conjunction with rotary root canal preparation. The experimental aqueous gel consisted of (w/v) 2% alginate, 3% aerosil, 10% Tween 80 and 18% HEBP. Interactions of gel components with hypochlorite were assessed using iodometric titration and monochromatic ultraviolet spectrometry. Two commercial paste-type chelators containing ethylenediaminetetraacetic acid (EDTA) and peroxide (RC-Prep and Glyde) served as controls. Calcium-binding capacities were measured in mixtures with a Ca2+ standard solution buffered at pH 10 using a calcium-selective measuring chain. Finally, root canals of 16 extracted single-rooted premolars per group were instrumented using ProFile instruments dipped in the experimental gel, RC-Prep, or nothing. Additionally, canals were rinsed with 10 mL of a 1% NaOCl solution during/after preparation. Smear scores in instrumented teeth were monitored using scanning electron microscopy. None of the experimental gel components showed short-term interactions with hypochlorite, whilst EDTA, peroxide, RC-Prep and Glyde immediately reduced the hypochlorite in solution. The experimental gel chelated 30 mg Ca2+ g-1, compared with 16 mg Ca2+ g-1 and 11 mg Ca2+ g-1 chelated by RC-Prep and Glyde respectively. Smear scores obtained with the experimental gel were significantly (P<0.05) lower than with RC-Prep in coronal and middle root thirds, whilst no differences were observed in apical root thirds. Under the conditions of this study, an HEBP gel appeared advantageous over currently available products.

Spectroscopic properties and Judd-Ofelt theory analysis of erbium chelates.

PubMed

Wang, Huaishan; Qian, Guodong; Wang, Zhiyu; Wang, Minquan

2005-11-01

Erbium chelates including tris(acetylacetonato) erbium(III) monohydrate, tris(acetylacetonato)(1,10-phenanthroline) erbium(III) and tris(trifluoroacetylacetonato)(1,10-phenanthroline) erbium(III) are synthesized. Judd-Ofelt theory is employed on basis of the UV-Vis-NIR absorption spectra of erbium chelates dissolved in methanol. Judd-Ofelt parameters of erbium chelates are determined by a least square fitting and dealt with the chemical structure of erbium chelates. Photoluminescence characteristics of erbium chelates are investigated upon excitation at 488 nm by an Ar(+) laser. The qualitative correlation of Judd-Ofelt parameters with photoluminescence properties for erbium chelates is also discussed. It is found that larger Omega(6) value for erbium chelate is and larger photoluminescence intensity at 1.54 microm is, and Omega(2) value should contribute to the photoluminescence full width at half maximum (FWHM) at 1.54 microm. The changes of Judd-Ofelt parameters result from the introduction of the second ligand phenathroline or the substitution of electron-drawing group CF(3) in beta-diketone for erbium chelates.

Retention of gadolinium compounds used in magnetic resonance imaging: a critical review and the recommendations of regulatory agencies.

PubMed

Martí-Bonmatí, L; Martí-Bonmatí, E

The Spanish Agency for Drugs and Healthcare Products (AEMPS), based on the recommendations of the European Committee for Risk Assessment in Pharmacovigilance, established on 13 March 2017 that linear gadolinium-based MR contrast media, such as MultiHance, Omniscan, Magnevist (currently not marketed) and Optimark (no longer marketed in Spain), the clinical benefits do not outweigh the potential risks derived from their use. AEMPS recommends to suspend its marketing for general use based on the retention of these compounds in the brain. On the other hand, the AEMPS justifies the maintenance of Primovist and MultiHance for liver studies, and Magnevist of intra-articular administration (not commercialized in Spain), and justified the almost exclusive use of macrocyclic structure contrasts (Gadovist, ProHance and Dotarem). However, this retention is known to be different for each of the contrast media. All existing gadolinium contrasts agents have a distribution phase with tissue retention, due to a very slow exchange, in the interstitium of bone, skin, kidney, brain and other organs. The existence of histological effects or clinical symptoms associated with the accumulation of these trace amounts of gadolinium has not been demonstrated. The major toxicological concern with these contrast agents is related to nephrogenic systemic fibrosis (NSF). Since the safety profiles are mainly related to the interstitial retention space in the tissues, it does not seem justified to actually exclude contrast media that do not have cases related to the NSF. Based on all of this, we disagree with the latest AEMPS recommendation suggesting the marketing stoppage of linear agents without considering the individual retention profiles. This recommendation is not based neither on the data nor existing knowledge about the retention, relaxivity and clinical efficiency of the Gd compounds. It is therefore necessary to carry out prospective studies on the histological and clinical relevance of these organic Gd deposits. Copyright © 2017 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

Tumor Xenograft Response to Redox-Active Therapies Assessed by Magnetic Resonance Imaging Using a Thiol-Bearing DOTA Complex of Gadolinium1

PubMed Central

Guntle, Gerald P; Jagadish, Bhumasamudram; Mash, Eugene A; Powis, Garth; Dorr, Robert T; Raghunand, Natarajan

2012-01-01

Gd-LC6-SH is a thiol-bearing DOTA complex of gadolinium designed to bind plasma albumin at the conserved Cys34 site. The binding of Gd-LC6-SH shows sensitivity to the presence of competing thiols. We hypothesized that Gd-LC6-SH could provide magnetic resonance imaging (MRI) enhancement that is sensitive to tumor redox state and that the prolonged retention of albumin-bound Gd-LC6-SH in vivo can be exploited to identify a saturating dose above which the shortening of MRI longitudinal relaxation time (T1) of tissue is insensitive to the injected gadolinium dose. In the Mia-PaCa-2 pancreatic tumor xenograft model in SCID mice, both the small-molecule Gd-DTPA-BMA and the macromolecule Galbumin MRI contrast agents produced dose-dependent decreases in tumor T1. By contrast, the decreases in tumor T1 provided by Gd-LC6-SH at 0.05 and 0.1 mmol/kg were not significantly different at longer times after injection. SCID mice bearing Mia-PaCa-2 or NCI-N87 tumor xenografts were treated with either the glutathione synthesis inhibitor buthionine sulfoximine or the thiol-oxidizing anticancer drug Imexon, respectively. In both models, there was a significantly greater increase in tumor R1 (=1/T1) 60 minutes after injection of Gd-LC6-SH in drug-treated animals relative to saline-treated controls. In addition, Mercury Orange staining for nonprotein sulfhydryls was significantly decreased by drug treatment relative to controls in both tumor models. In summary, these studies show that thiol-bearing complexes of gadolinium such as Gd-LC6-SH can serve as redox-sensitive MRI contrast agents for detecting differences in tumor redox status and can be used to evaluate the effects of redox-active drugs. PMID:22741038

Decision points in the treatment of transfusional iron overload in patients with myelodysplastic syndromes: why, when, and how to chelate.

PubMed

Imran, Farhan; Phatak, Pradyumna

2017-01-01

Patients with myelodysplastic syndromes (MDS) differ from those with other transfusion-dependent conditions (eg, thalassemia) as they are typically older, have comorbid conditions, and a generally shorter life expectancy. The underlying disease process in MDS and frequent use of red blood cell transfusions lead to iron accumulation and ultimately organ damage. Whether iron-reducing interventions such as chelation therapy can improve outcomes in this population is currently under investigation. Areas covered: We reviewed published English-language articles from PubMed on the topic of iron overload (IO) in MDS, and the use of iron chelation therapies (ICTs) to alleviate iron burden. Expert commentary: Data on IO-associated complications in MDS are derived largely from retrospective studies and there are limited data to guide clinicians on major treatment decisions. Although effective and well-tolerated oral ICTs are available, and general recommendations may be made regarding usage in MDS, guidance is not yet based on prospective data. The clinical endpoints and assessments for MDS may differ substantively from those used in patients with thalassemia, as an older population may have competing causes for morbidity. We expect that emergent data from clinical trials currently underway will define more appropriate endpoints/assessments for the MDS population in clinical trials.

Deferasirox, an oral iron chelator, prevents hepatocarcinogenesis and adverse effects of sorafenib

PubMed Central

Yamamoto, Naoki; Yamasaki, Takahiro; Takami, Taro; Uchida, Koichi; Fujisawa, Koichi; Matsumoto, Toshihiko; Saeki, Issei; Terai, Shuji; Sakaida, Isao

2016-01-01

Although sorafenib is expected to have a chemopreventive effect on hepatocellular carcinoma (HCC) recurrence, there are limitations to its use because of adverse effects, including effects on liver function. We have reported that the iron chelator, deferoxamine can prevent liver fibrosis and preneoplastic lesions. We investigated the influence of administering a new oral iron chelator, deferasirox (DFX), on the effects of sorafenib. We used the choline-deficient l-amino acid-defined (CDAA) diet-induced rat liver fibrosis and HCC model. We divided rats into four groups: CDAA diet only (control group), CDAA diet with sorafenib (sorafenib group), CDAA diet with DFX (DFX group), and CDAA diet with DFX and sorafenib (DFX + sorafenib group). Liver fibrosis and development of preneoplastic lesions were assessed. In addition, we assessed adverse effects such as changes in body and liver weight, skin damage (eruption, dryness, and hair loss), which is defined as hand-foot skin syndrome, in the sorafenib and DFX + sorafenib groups. The combination of DFX + sorafenib markedly prevented liver fibrosis and preneoplastic lesions better than the other treatments. Furthermore, the combination therapy significantly decreased adverse effects compared with the sorafenib group. In conclusion, the combination therapy with DFX and sorafenib may be a useful adjuvant therapy to prevent recurrence after curative treatment of HCC. PMID:27257345

Deferasirox, an oral iron chelator, prevents hepatocarcinogenesis and adverse effects of sorafenib.

PubMed

Yamamoto, Naoki; Yamasaki, Takahiro; Takami, Taro; Uchida, Koichi; Fujisawa, Koichi; Matsumoto, Toshihiko; Saeki, Issei; Terai, Shuji; Sakaida, Isao

2016-05-01

Although sorafenib is expected to have a chemopreventive effect on hepatocellular carcinoma (HCC) recurrence, there are limitations to its use because of adverse effects, including effects on liver function. We have reported that the iron chelator, deferoxamine can prevent liver fibrosis and preneoplastic lesions. We investigated the influence of administering a new oral iron chelator, deferasirox (DFX), on the effects of sorafenib. We used the choline-deficient l-amino acid-defined (CDAA) diet-induced rat liver fibrosis and HCC model. We divided rats into four groups: CDAA diet only (control group), CDAA diet with sorafenib (sorafenib group), CDAA diet with DFX (DFX group), and CDAA diet with DFX and sorafenib (DFX + sorafenib group). Liver fibrosis and development of preneoplastic lesions were assessed. In addition, we assessed adverse effects such as changes in body and liver weight, skin damage (eruption, dryness, and hair loss), which is defined as hand-foot skin syndrome, in the sorafenib and DFX + sorafenib groups. The combination of DFX + sorafenib markedly prevented liver fibrosis and preneoplastic lesions better than the other treatments. Furthermore, the combination therapy significantly decreased adverse effects compared with the sorafenib group. In conclusion, the combination therapy with DFX and sorafenib may be a useful adjuvant therapy to prevent recurrence after curative treatment of HCC.

Prospective evaluation of the effect of deferasirox on hematologic response in transfusion-dependent patients with low-risk MDS and iron overload.

PubMed

Rose, Christian; Lenoir, Caroline; Gyan, Emmanuel; Hacini, Maya; Amé, Shanti; Corront, Bernadette; Beyne-Rauzy, Odile; Adiko, Didier; Loppinet, Elena; Ali-Ammar, Nadia; Laribi, Kamel; Wattel, Eric; Dreyfus, François; Roué, Claire S; Cheze, Stephane

2018-05-02

To assess the reduction of transfusions rate in transfusion-dependent patients with low-risk myelodysplastic syndrome (MDS) with iron overload treated with deferasirox. Prospective observational study. Primary endpoint was reduction in transfusion requirements (RTR) at 3 months, (assessed on 8-week period). Secondary endpoints were hematologic improvement according to International Working Group (IWG) 2006 criteria at 3, 6, and 12 months. Fifty-seven patients were evaluable. After 3 months of chelation, no effect was seen on transfusion requirement (5.9 packed red blood cells (PRBC) vs 5.8 before chelation). According to the Kaplan-Meier analysis, the probability of RTR at 3, 6, and 12 months was assessed as 3.5%, 9.1%, and 18.7%, respectively. Median duration of RTR was 182 days. However, during the 12-month follow-up after deferasirox initiation, 17 patients (31.5%) achieved minor erythroid response [HI-E] according to IWG criteria, 10 of whom having achieved Hb improvement at month 12. After 3 months of treatment, deferasirox had no impact on transfusion requirement in regularly transfused patients with low-risk MDS. However, deferasirox could induce 31% of erythroid response during the 12-month follow-up period thus suggesting that iron chelation therapy with deferasirox may induce an effect on hematopoiesis in a subset of patients with MDS and iron overload. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Measurement of gamma-ray production from thermal neutron capture on gadolinium for neutrino experiments

NASA Astrophysics Data System (ADS)

Yano, Takatomi; 2012B0025 Collaboration; 2014B0126 Collaboration

2017-02-01

Recently, several scientific applications of gadolinium are found in neutrino physics experiments. Gadolinium-157 is the nucleus, which has the largest thermal neutron capture cross-section among all stable nuclei. Gadolinium-155 also has the large cross-section. These neutron capture reactions provide the gamma-ray cascade with the total energy of about 8 MeV. This reaction is applied for several neutrino experiments, e.g. reactor neutrino experiments and Gd doped large water Cherenkov detector experiments, to recognize inverse-beta-decay reaction. A good Gd(n,γ) simulation model is needed to evaluate the detection efficiency of the neutron capture reaction, i.e. the efficiency of IBD detection. In this presentation, we will report the development and study status of a Gd(n,γ) calculation model and comparison with our experimental data taken at ANNRI/MLF beam line, J-PARC.

A comparison of the COG and MCNP codes in computational neutron capture therapy modeling, Part II: gadolinium neutron capture therapy models and therapeutic effects.

PubMed

Wangerin, K; Culbertson, C N; Jevremovic, T

2005-08-01

The goal of this study was to evaluate the COG Monte Carlo radiation transport code, developed and tested by Lawrence Livermore National Laboratory, for gadolinium neutron capture therapy (GdNCT) related modeling. The validity of COG NCT model has been established for this model, and here the calculation was extended to analyze the effect of various gadolinium concentrations on dose distribution and cell-kill effect of the GdNCT modality and to determine the optimum therapeutic conditions for treating brain cancers. The computational results were compared with the widely used MCNP code. The differences between the COG and MCNP predictions were generally small and suggest that the COG code can be applied to similar research problems in NCT. Results for this study also showed that a concentration of 100 ppm gadolinium in the tumor was most beneficial when using an epithermal neutron beam.

Nephrogenic systemic fibrosis (NSF): a late adverse reaction to some of the gadolinium based contrast agents

PubMed Central

Marckmann, Peter; Logager, Vibeke B.

2007-01-01

Abstract Until recently it was believed that extracellular gadolinium based contrast agents were safe for both the kidneys and all other organs within the dose range up to 0.3 mmol/kg body weight. However, in 2006, it was demonstrated that some gadolinium based contrast agents may trigger the development of nephrogenic systemic fibrosis, a generalised fibrotic disorder, in renal failure patients. Accordingly, the use of gadodiamide and gadopentate dimeglumine for renal failure patients was banned in Europe in spring 2007. The same two compounds should only be used cautiously in patients with moderate renal dysfunction. The current paper reviews the situation (July 2007) regarding gadolinium based contrast agent and the severe delayed reaction to some of these agents. The fear of nephrogenic systemic fibrosis should not lead to a denial of a well indicated enhanced magnetic resonance imaging examination. PMID:17905680

Gadolinium-enhanced computed tomographic angiography: current status.

PubMed

Rosioreanu, Alex; Alberico, Ronald A; Litwin, Alan; Hon, Man; Grossman, Zachary D; Katz, Douglas S

2005-01-01

This article reviews the research to date, as well as our clinical experience from two institutions, on gadolinium-enhanced computed tomographic angiography (gCTA) for imaging the body. gCTA may be an appropriate examination for the small percentage of patients who would benefit from noninvasive vascular imaging, but who have contraindications to both iodinated contrast and magnetic resonance imaging. gCTA is more expensive than CTA with iodinated contrast, due to the dose of gadolinium administered, and gCTA has limitations compared with CTA with iodinated contrast, in that parenchymal organs are not optimally enhanced at doses of 0.5 mmol/kg or lower. However, in our experience, gCTA has been a very useful problem-solving examination in carefully selected patients. With the advent of 16-64 detector CT, in combination with bolus tracking, we believe that the overall dose of gadolinium needed for diagnostic CTA examinations, while relatively high, can be safely administered.

Room temperature ferromagnetic gadolinium silicide nanoparticles

DOEpatents

Hadimani, Magundappa Ravi L.; Gupta, Shalabh; Harstad, Shane; Pecharsky, Vitalij; Jiles, David C.

2018-03-06

A particle usable as T₁ and T₂ contrast agents is provided. The particle is a gadolinium silicide (Gd₅Si₄) particle that is ferromagnetic at temperatures up to 290 K and is less than 2 .mu.m in diameter. An MRI contrast agent that includes a plurality of gadolinium silicide (Gd.sub.5Si.sub.4) particles that are less than 1 .mu.m in diameter is also provided. A method for creating gadolinium silicide (Gd₅Si₄) particles is also provided. The method includes the steps of providing a Gd₅Si₄ bulk alloy; grinding the Gd₅Si₄ bulk alloy into a powder; and milling the Gd₅Si₄ bulk alloy powder for a time of approximately 20 minutes or less.

Biocompatible blood pool MRI contrast agents based on hyaluronan

PubMed Central

Zhu, Wenlian; Artemov, Dmitri

2010-01-01

Biocompatible gadolinium blood pool contrast agents based on a biopolymer, hyaluronan, were investigated for magnetic resonance angiography application. Hyaluronan, a non-sulfated linear glucosaminoglycan composed of 2000–25,000 repeating disaccharide subunits of D-glucuronic acid and N-acetylglucosamine with molecular weight up to 20 MDa, is a major component of the extracellular matrix. Two gadolinium contrast agents based on 16 and 74 kDa hyaluronan were synthesized, both with R1 relaxivity around 5 mM−1 s−1 per gadolinium at 9.4 T at 25°C. These two hyaluronan based agents show significant enhancement of the vasculature for an extended period of time. Initial excretion was primarily through the renal system. Later uptake was observed in the stomach and lower gastrointestinal tract. Macromolecular hyaluronan-based gadolinium agents have a high clinical translation potential as hyaluronan is already approved by FDA for a variety of medical applications. PMID:21504061

The network formers role of gadolinium(III) ions in some zinc-borate glass ceramics

NASA Astrophysics Data System (ADS)

Bosca, Maria; Pop, Lidia; Pascuta, Petru

2017-12-01

EPR and magnetic susceptibility measurements were performed on glass ceramics from the (Gd2O3)x.(B2O3)(60-x).(ZnO)40 system, with 0 ≤ x ≤ 15 mol%, in order to determine the role of gadolinium ions on structural and magnetic properties. At low Gd2O3 contents (x ≤ 1 mol%) the EPR spectra show four resonance lines with effective g-values of ˜ 6, 4.8, 2.8 and 2, typical for Gd3+ ions uniformly distributed in the glass and glass ceramic samples. For higher contents of gadolinium ions (x ≥ 3 mol%) the EPR spectra are dominated by a single broad line centered at g ˜ 2, which can be due to the magnetic clusters containing Gd3+ ions. The magnetic susceptibility data show that the gadolinium ions are involved in superexchange interactions in all the investigated glass ceramics, being antiferromagnetically coupled.

EDTA chelation therapy alone and in combination with oral high-dose multivitamins and minerals for coronary disease: The factorial group results of the Trial to Assess Chelation Therapy.

PubMed

Lamas, Gervasio A; Boineau, Robin; Goertz, Christine; Mark, Daniel B; Rosenberg, Yves; Stylianou, Mario; Rozema, Theodore; Nahin, Richard L; Terry Chappell, L; Lindblad, Lauren; Lewis, Eldrin F; Drisko, Jeanne; Lee, Kerry L

2014-07-01

Disodium ethylenediaminetetraacetic acid (EDTA) reduced adverse cardiac outcomes in a factorial trial also testing oral vitamins. This report describes the intent-to-treat comparison of the 4 factorial groups overall and in patients with diabetes. This was a double-blind, placebo-controlled, 2 × 2 factorial multicenter randomized trial of 1,708 post-myocardial infarction (MI) patients ≥50 years of age and with creatinine ≤2.0 mg/dL randomized to receive 40 EDTA chelation or placebo infusions plus 6 caplets daily of a 28-component multivitamin-multimineral mixture or placebo. The primary end point was a composite of total mortality, MI, stroke, coronary revascularization, or hospitalization for angina. Median age was 65 years, 18% were female, 94% were Caucasian, 37% were diabetic, 83% had prior coronary revascularization, and 73% were on statins. Five-year Kaplan-Meier estimates for the primary end point was 31.9% in the chelation + high-dose vitamin group, 33.7% in the chelation + placebo vitamin group, 36.6% in the placebo infusion + active vitamin group, and 40.2% in the placebo infusions + placebo vitamin group. The reduction in primary end point by double active treatment compared with double placebo was significant (hazard ratio 0.74, 95% CI 0.57-0.95, P = .016). In patients with diabetes, the primary end point reduction of double active compared with double placebo was more pronounced (hazard ratio 0.49, 95% CI 0.33-0.75, P < .001). In stable post-MI patients on evidence-based medical therapy, the combination of oral high-dose vitamins and chelation therapy compared with double placebo reduced clinically important cardiovascular events to an extent that was both statistically significant and of potential clinical relevance. Copyright © 2014 The Authors. Published by Mosby, Inc. All rights reserved.

Heavy Metals, Cardiovascular Disease, and the Unexpected Benefits of Edetate Disodium Chelation Therapy

PubMed Central

Lamas, Gervasio A.; Navas-Acien, Ana; Mark, Daniel B.; Lee, Kerry L.

2016-01-01

This review summarizes evidence from 2 lines of research previously thought unrelated: the unexpectedly positive results of the Trial to Assess Chelation Therapy (TACT), and a body of epidemiological data showing that accumulation of biologically active metals, such as lead and cadmium, is an important risk factor for cardiovascular disease. Considering these 2 areas of work together may lead to the identification of new, modifiable risk factors for atherosclerotic cardiovascular disease. We examine the history of chelation up through the report of TACT. We then describe work connecting higher metal levels in the body with the future risk of cardiovascular disease. We conclude by presenting a brief overview of a newly planned National Institutes of Health trial, TACT2, in which we will attempt to replicate the findings of TACT and to establish that removal of toxic metal stores from the body is a plausible mechanistic explanation for the benefits of edetate disodium treatment. PMID:27199065

Heavy Metals, Cardiovascular Disease, and the Unexpected Benefits of Chelation Therapy.

PubMed

Lamas, Gervasio A; Navas-Acien, Ana; Mark, Daniel B; Lee, Kerry L

2016-05-24

This review summarizes evidence from 2 lines of research previously thought to be unrelated: the unexpectedly positive results of TACT (Trial to Assess Chelation Therapy), and a body of epidemiological data showing that accumulation of biologically active metals, such as lead and cadmium, is an important risk factor for cardiovascular disease. Considering these 2 areas of work together may lead to the identification of new, modifiable risk factors for atherosclerotic cardiovascular disease. We examine the history of chelation up through the report of TACT. We then describe work connecting higher metal levels in the body with the future risk of cardiovascular disease. We conclude by presenting a brief overview of a newly planned National Institutes of Health trial, TACT2, in which we will attempt to replicate the findings of TACT and to establish that removal of toxic metal stores from the body is a plausible mechanistic explanation for the benefits of edetate disodium treatment. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Performance of Nonmigratory Iron Chelating Active Packaging Materials in Viscous Model Food Systems.

PubMed

Roman, Maxine J; Decker, Eric A; Goddard, Julie M

2015-09-01

Many packaged food products undergo quality deterioration due to iron promoted oxidative reactions. Recently, we have developed a nonmigratory iron chelating active packaging material that represents a novel approach to inhibit oxidation of foods while addressing consumer demands for "cleanˮ labels. A challenge to the field of nonmigratory active packaging is ensuring that surface-immobilized active agents retain activity in a true food system despite diffusional limitations. Yet, the relationship between food viscosity and nonmigratory active packaging activity retention has never been characterized. The objective of this study was to investigate the influence of food viscosity on iron chelation by a nonmigratory iron chelating active packaging material. Methyl cellulose was added to aqueous buffered iron solutions to yield model systems with viscosities ranging from ∼1 to ∼10(5)  mPa·s, representing viscosities ranging from beverage to mayonnaise. Iron chelation was quantified by material-bound iron content using colorimetry and inductively coupled plasma-optical emission spectrometry (ICP-OES).  Maximum iron chelation was reached in solutions up to viscosity ∼10(2)  mPa·s. In more viscous solutions (up to ∼10(4)  mPa·s), there was a significant decrease in iron chelating capacity (P < 0.05). However, materials still retained at least 76% iron chelating capacity. Additionally, the influence of different food hydrocolloids on the performance of nonmigratory iron chelating active packaging was characterized. Methyl cellulose and carrageenan did not compete with the material for specific iron chelation (P > 0.05). Materials retained 32% to 45% chelating capacity when in contact with competitively chelating hydrocolloids guar gum, locust bean gum, and xanthan gum. This work demonstrates the potential application of nonmigratory iron chelating active packaging in liquid and semi-liquid foods to allow for the removal of synthetic chelators, while maintaining food quality. © 2015 Institute of Food Technologists®

Luminescent lanthanide chelates and methods of use

DOEpatents

Selvin, Paul R.; Hearst, John

1997-01-01

The invention provides lanthanide chelates capable of intense luminescence. The celates comprise a lanthanide chelator covalently joined to a coumarin-like or quinolone-like sensitizer. Exemplary sensitzers include 2- or 4-quinolones, 2- or 4-coumarins, or derivatives thereof e.g. carbostyril 124 (7-amino-4-methyl-2-quinolone), coumarin 120 (7-amino-4-methyl-2-coumarin), coumarin 124 (7-amino-4-(trifluoromethyl)-2-coumarin), aminomethyltrimethylpsoralen, etc. The chelates form high affinity complexes with lanthanides, such as terbium or europium, through chelator groups, such as DTPA. The chelates may be coupled to a wide variety of compounds to create specific labels, probes, diagnostic and/or therapeutic reagents, etc. The chelates find particular use in resonance energy transfer between chelate-lanthanide complexes and another luminescent agent, often a fluorescent non-metal based resonance energy acceptor. The methods provide useful information about the structure, conformation, relative location and/or interactions of macromolecules.

Obligatory reduction of ferric chelates in iron uptake by soybeans.

PubMed

Chaney, R L; Brown, J C; Tiffin, L O

1972-08-01

The contrasting Fe(2+) and Fe(3+) chelating properties of the synthetic chelators ethylenediaminedi (o-hydroxyphenylacetate) (EDDHA) and 4,7-di(4-phenylsulfonate)-1, 10-phenanthroline (bathophenanthrolinedisulfonate) (BPDS) were used to determine the valence form of Fe absorbed by soybean roots supplied with Fe(3+)-chelates. EDDHA binds Fe(3+) strongly, but Fe(2+) weakly; BPDS binds Fe(2+) strongly but Fe(3+) weakly. Addition of an excess of BPDS to nutrient solutions containing Fe(3+)-chelates inhibited soybean Fe uptake-translocation by 99+%; [Fe(II) (BPDS)(3)](4-) accumulated in the nutrient solution. The addition of EDDHA caused little or no inhibition. These results were observed with topped and intact soybeans. Thus, separation and absorption of Fe from Fe(3+)-chelates appear to require reduction of Fe(3+)-chelate to Fe(2+)-chelate at the root, with Fe(2+) being the principal form of Fe absorbed by soybean.

Ultra-wide range field-dependent measurements of the relaxivity of Gd1−xEuxVO4 nanoparticle contrast agents using a mechanical sample-shuttling relaxometer

PubMed Central

Chou, Ching-Yu; Abdesselem, Mouna; Bouzigues, Cedric; Chu, Minglee; Guiga, Angelo; Huang, Tai-Huang; Ferrage, Fabien; Gacoin, Thierry; Alexandrou, Antigoni; Sakellariou, Dimitris

2017-01-01

The current trend for Magnetic Resonance Imaging points towards higher magnetic fields. Even though sensitivity and resolution are increased in stronger fields, T1 contrast is often reduced, and this represents a challenge for contrast agent design. Field-dependent measurements of relaxivity are thus important to characterize contrast agents. At present, the field-dependent curves of relaxivity are usually carried out in the field range of 0 T to 2 T, using fast field cycling relaxometers. Here, we employ a high-speed sample shuttling device to switch the magnetic fields experienced by the nuclei between virtually zero field, and the center of any commercial spectrometer. We apply this approach on rare-earth (mixed Gadolinium-Europium) vanadate nanoparticles, and obtain the dispersion curves from very low magnetic field up to 11.7 T. In contrast to the relaxivity profiles of Gd chelates, commonly used for clinical applications, which display a plateau and then a decrease for increasing magnetic fields, these nanoparticles provide maximum contrast enhancement for magnetic fields around 1–1.5 T. These field-dependent curves are fitted using the so-called Magnetic Particle (MP) model and the extracted parameters discussed as a function of particle size and composition. We finally comment on the new possibilities offered by this approach. PMID:28317892

Impaired glymphatic perfusion after strokes revealed by contrast-enhanced MRI: a new target for fibrinolysis?

PubMed

Gaberel, Thomas; Gakuba, Clement; Goulay, Romain; Martinez De Lizarrondo, Sara; Hanouz, Jean-Luc; Emery, Evelyne; Touze, Emmanuel; Vivien, Denis; Gauberti, Maxime

2014-10-01

The aim of the present study was to investigate the impact of different stroke subtypes on the glymphatic system using MRI. We first improved and characterized an in vivo protocol to measure the perfusion of the glymphatic system using MRI after minimally invasive injection of a gadolinium chelate within the cisterna magna. Then, the integrity of the glymphatic system was evaluated in 4 stroke models in mice including subarachnoid hemorrhage (SAH), intracerebral hemorrhage, carotid ligature, and embolic ischemic stroke. We were able to reliably evaluate the glymphatic system function using MRI. Moreover, we provided evidence that the glymphatic system was severely impaired after SAH and in the acute phase of ischemic stroke, but was not altered after carotid ligature or in case of intracerebral hemorrhage. Notably, this alteration in glymphatic perfusion reduced brain clearance rate of low-molecular-weight compounds. Interestingly, glymphatic perfusion after SAH can be improved by intracerebroventricular injection of tissue-type plasminogen activator. Moreover, spontaneous arterial recanalization was associated with restoration of the glymphatic function after embolic ischemic stroke. SAH and acute ischemic stroke significantly impair the glymphatic system perfusion. In these contexts, injection of tissue-type plasminogen activator either intracerebroventricularly to clear perivascular spaces (for SAH) or intravenously to restore arterial patency (for ischemic stroke) may improve glymphatic function. © 2014 American Heart Association, Inc.

Geometrical confinement of Gd(DOTA) molecules within mesoporous silicon nanoconstructs for MR imaging of cancer

PubMed Central

Gizzatov, Ayrat; Stigliano, Cinzia; Ananta, Jeyerama S.; Sethi, Richa; Xu, Rong; Guven, Adem; Ramirez, Maricela; Shen, Haifa; Sood, Anil; Ferrari, Mauro; Wilson, Lon J.; Liu, Xuewu; Decuzzi, Paolo

2015-01-01

Porous silicon has been used for the delivery of therapeutic and imaging agents in several biomedical applications. Here, mesoporous silicon nanoconstructs (SiMPs) with a discoidal shape and a sub-micrometer size (1,000 × 400 nm) have been conjugated with gadolinium-tetraazacyclododecane tetraacetic acid Gd(DOTA) molecules and proposed as contrast agents for Magnetic Resonance Imaging. The surface of the SiMPs with different porosities – small pore (SP: ~ 5 nm) and huge pore (HP: ~ 40 nm) – and of bulk, non-porous silica beads (1,000 nm in diameter) have been modified with covalently attached (3-aminopropyl)triethoxysilane (APTES) groups, conjugated with DOTA molecules, and reacted with an aqueous solution of GdCl3. The resulting Gd(DOTA) molecules confined within the small pores of the Gd-SiMPs achieve longitudinal relaxivities r1 of ~ 17 (mM·s)−1, which is 4 times greater than for free Gd(DOTA). This enhancement is ascribed to the confinement and stable chelation of Gd(DOTA) molecules within the SiMP mesoporous matrix. The resulting nanoconstructs possess no cytotoxicity and accumulate in ovarian tumors up to 2% of the injected dose per gram tissue, upon tail vein injection. All together this data suggests that Gd-SiMPs could be efficiently used for MR vascular imaging in cancer and other diseases. PMID:24931336

Geometrical confinement of Gd(DOTA) molecules within mesoporous silicon nanoconstructs for MR imaging of cancer.

PubMed

Gizzatov, Ayrat; Stigliano, Cinzia; Ananta, Jeyerama S; Sethi, Richa; Xu, Rong; Guven, Adem; Ramirez, Maricela; Shen, Haifa; Sood, Anil; Ferrari, Mauro; Wilson, Lon J; Liu, Xuewu; Decuzzi, Paolo

2014-09-28

Porous silicon has been used for the delivery of therapeutic and imaging agents in several biomedical applications. Here, mesoporous silicon nanoconstructs (SiMPs) with a discoidal shape and a sub-micrometer size (1000×400nm) have been conjugated with gadolinium-tetraazacyclododecane tetraacetic acid Gd(DOTA) molecules and proposed as contrast agents for Magnetic Resonance Imaging. The surface of the SiMPs with different porosities - small pore (SP: ∼5nm) and huge pore (HP: ∼40nm) - and of bulk, non-porous silica beads (1000nm in diameter) have been modified with covalently attached (3-aminopropyl)triethoxysilane (APTES) groups, conjugated with DOTA molecules, and reacted with an aqueous solution of GdCl3. The resulting Gd(DOTA) molecules confined within the small pores of the Gd-SiMPs achieve longitudinal relaxivities r1 of ∼17 (mMs)(-)(1), which is 4 times greater than for free Gd(DOTA). This enhancement is ascribed to the confinement and stable chelation of Gd(DOTA) molecules within the SiMP mesoporous matrix. The resulting nanoconstructs possess no cytotoxicity and accumulate in ovarian tumors up to 2% of the injected dose per gram tissue, upon tail vein injection. All together this data suggests that Gd-SiMPs could be efficiently used for MR vascular imaging in cancer and other diseases. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

On the Role of low-energy electrons in the radiosensitization of DNA by gold nanoparticles

PubMed Central

Xiao, Fangxing; Zheng, Yi; Cloutier, Pierre; He, Yunhui; Hunting, Darel; Sanche, Léon

2013-01-01

Four different gold nanoparticle (GNP) preparations, including nude GNP and GNP coated either with thiolated undecane (S-C11H23), or with dithiolated diethylenetriaminepentaacetic (DTDTPA) or gadolinium (Gd) DTDTPA chelating agents were synthesized. The average diameters, for each type of nanoparticle are 5 nm, 10 and 13 nm, respectively. Dry films of plasmid DNA pGEM-3Zf(-), DNA with bound GNP and DNA with coated GNP were bombarded with 60 keV electrons. The yields of single and double strand breaks were measured as a function of exposure by electrophoresis. The binding of only one GNP without coating to DNA containing 3197 base pairs increases single and double strand breaks by a factor of 2.3 while for GNP coated with S-C11H23 this factor is reduced to 1.6. GNP coated with the DTDTPA and DTDTPA:Gd in same ratio with DNA, produce essentially no increment in damage. These results could be explained by the attenuation by the coatings of the intensity of low energy photoelectrons emitted from GNP. Thus, coatings of GNP may considerably attenuate short-range low energy electrons emitted from gold, leading to a considerable decrease of radiosensitization. According to our results, the highest radiosensitization should be obtained with GNP having the shortest possible ligand, directed to the DNA of cancer cells. PMID:22024607

Characterization of Gd loaded chitosan-TPP nanohydrogels by a multi-technique approach combining dynamic light scattering (DLS), asymetrical flow-field-flow-fractionation (AF4) and atomic force microscopy (AFM) and design of positive contrast agents for molecular resonance imaging (MRI)

NASA Astrophysics Data System (ADS)

Rigaux, G.; Gheran, C. V.; Callewaert, M.; Cadiou, C.; Voicu, S. N.; Dinischiotu, A.; Andry, M. C.; Vander Elst, L.; Laurent, S.; Muller, R. N.; Berquand, A.; Molinari, M.; Huclier-Markai, S.; Chuburu, F.

2017-02-01

Chitosan CS—tripolyphosphate TPP/hyaluronic acid HA nanohydrogels loaded with gadolinium chelates (GdDOTA ⊂ CS-TPP/HA NGs) synthesized by ionic gelation were designed for lymph node (LN) MRI. In order to be efficiently drained to LNs, nanogels (NGs) needed to exhibit a diameter ϕ < 100 nm. For that, formulation parameters were tuned, using (i) CS of two different molecular weights (51 and 37 kDa) and (ii) variable CS/TPP ratio (2 < CS/TPP < 8). Characterization of NG size distribution by dynamic light scattering (DLS) and asymetrical flow-field-flow-fractionation (AF4) showed discrepancies since DLS diameters were consistently above 200 nm while AF4 showed individual nano-objects with ϕ < 100 nm. Such a difference could be correlated to the presence of aggregates inherent to ionic gelation. This point was clarified by atomic force microscopy (AFM) in liquid mode which highlighted the main presence of individual nano-objects in nanosuspensions. Thus, combination of DLS, AF4 and AFM provided a more precise characterization of GdDOTA ⊂ CS-TPP/HA nanohydrogels which, in turn, allowed to select formulations leading to NGs of suitable mean sizes showing good MRI efficiency and negligible toxicity.

[Susceptibility of enterococci to natural and synthetic iron chelators].

PubMed

Lisiecki, Paweł; Mikucki, Jerzy

2002-01-01

A total of 79 strains of enterococci belonging to 10 species were tested for susceptibility to natural and synthetic iron chelators. All strains produced siderophores. These enterococci were susceptible to three synthetic iron chelators only: 8-hydroxyquinoline, disodium versenate (EDTA) and o-phenanthroline. They were resistant to all other synthetic chelators: ethylenediamine-di(o-hydroxyphenylacetic acid) (EDDHA), nitrilotriacetate, 2,2'-bipiridyl, salicylic acid, 8-hydroxy-5-sulphonic acid and to all natural chelators: ovotransferrine, human apotransferrine, horse apoferritine, desferrioxamine B, ferrichrome and rhodotorulic acid. The relations between susceptibility/resistance, iron assimilation and structure and stability constants of iron chelators were discussed.

Recovery of methamphetamine associated cardiomyopathy predicted by late gadolinium enhanced cardiovascular magnetic resonance.

PubMed

Lopez, Javier E; Yeo, Khung; Caputo, Gary; Buonocore, Michael; Schaefer, Saul

2009-11-11

Methamphetamine is known to cause a cardiomyopathy which may be reversible with appropriate medical therapy and cessation of use. Late gadolinium enhancement cardiovascular magnetic resonance (CMR) has been shown to identify fibrosis in ischemic and non-ischemic cardiomyopathies. We present a case of severe methamphetamine-associated cardiomyopathy in which cardiac function recovered after 6 months. Evaluation by CMR using late gadolinium enhancement was notable for an absence of enhancement, suggesting an absence of irreversible myocyte injury and a good prognosis. CMR may be useful to predict recovery in toxin-associated non-ischemic cardiomyopathies.

Recovery of methamphetamine associated cardiomyopathy predicted by late gadolinium enhanced cardiovascular magnetic resonance

PubMed Central

2009-01-01

Methamphetamine is known to cause a cardiomyopathy which may be reversible with appropriate medical therapy and cessation of use. Late gadolinium enhancement cardiovascular magnetic resonance (CMR) has been shown to identify fibrosis in ischemic and non-ischemic cardiomyopathies. We present a case of severe methamphetamine-associated cardiomyopathy in which cardiac function recovered after 6 months. Evaluation by CMR using late gadolinium enhancement was notable for an absence of enhancement, suggesting an absence of irreversible myocyte injury and a good prognosis. CMR may be useful to predict recovery in toxin-associated non-ischemic cardiomyopathies. PMID:19906310

Accumulation of MRI contrast agents in malignant fibrous histiocytoma for gadolinium neutron capture therapy.

PubMed

Fujimoto, T; Ichikawa, H; Akisue, T; Fujita, I; Kishimoto, K; Hara, H; Imabori, M; Kawamitsu, H; Sharma, P; Brown, S C; Moudgil, B M; Fujii, M; Yamamoto, T; Kurosaka, M; Fukumori, Y

2009-07-01

Neutron-capture therapy with gadolinium (Gd-NCT) has therapeutic potential, especially that gadolinium is generally used as a contrast medium in magnetic resonance imaging (MRI). The accumulation of gadolinium in a human sarcoma cell line, malignant fibrosis histiocytoma (MFH) Nara-H, was visualized by the MRI system. The commercially available MRI contrast medium Gd-DTPA (Magnevist, dimeglumine gadopentetate aqueous solution) and the biodegradable and highly gadopentetic acid (Gd-DTPA)-loaded chitosan nanoparticles (Gd-nanoCPs) were prepared as MRI contrast agents. The MFH cells were cultured and collected into three falcon tubes that were set into the 3-tesra MRI system to acquire signal intensities from each pellet by the spin echo method, and the longitudinal relaxation time (T1) was calculated. The amount of Gd in the sample was measured by inductively coupled plasma atomic emission spectrography (ICP-AES). The accumulation of gadolinium in cells treated with Gd-nanoCPs was larger than that in cells treated with Gd-DTPA. In contrast, and compared with the control, Gd-DTPA was more effective than Gd-nanoCPs in reducing T1, suggesting that the larger accumulation exerted the adverse effect of lowering the enhancement of MRI. Further studies are warranted to gain insight into the therapeutic potential of Gd-NCT.

In vitro radiosensitizing effects of ultrasmall gadolinium based particles on tumour cells.

PubMed

Mowat, P; Mignot, A; Rima, W; Lux, F; Tillement, O; Roulin, C; Dutreix, M; Bechet, D; Huger, S; Humbert, L; Barberi-Heyob, M; Aloy, M T; Armandy, E; Rodriguez-Lafrasse, C; Le Duc, G; Roux, S; Perriat, P

2011-09-01

Since radiotherapy is widely used in cancer treatment, it is essential to develop strategies which lower the irradiation burden while increasing efficacy and become efficient even in radio resistant tumors. Our new strategy is relying on the development of solid hybrid nanoparticles based on rare-earth such as gadolinium. In this paper, we then evidenced that gadolinium-based particles can be designed to enter efficiently into the human glioblastoma cell line U87 in quantities that can be tuned by modifying the incubation conditions. These sub-5 nm particles consist in a core of gadolinium oxide, a shell of polysiloxane and are functionalized by diethylenetriaminepentaacetic acid (DTPA). Although photoelectric effect is maximal in the [10-100 keV] range, such particles were found to possess efficient in-vitro radiosensitizing properties at an energy of 660 keV by using the "single-cell gel electrophoresis comet assay," an assay that measures the number of DNA damage that occurs during irradiation. Even more interesting, the particles have been evidenced by MTT assays to be also efficient radiosensitizers at an energy of 6 MeV for doses comprised between 2 and 8 Gy. The properties of the gadolinium-based particles give promising opening to a particle-assisted radio-therapy by using irradiation systems already installed in the majority of hospitals.

Magnetic resonance imaging with gadolinium arthrography to assess acetabular cartilage delamination.

PubMed

Zaragoza, Edward; Lattanzio, Pierre-Jean; Beaule, Paul E

2009-01-01

Recent reports have demonstrated magnetic resonance imaging (MRI) as a promising technique in detecting articular cartilage lesions of the hip joint. The purpose of our study was to evaluate the diagnostic performance of MRI with gadolinium arthrography in detecting acetabular cartilage delamination in patients with pre-arthritic hip pain. 46 patients (48 hips) underwent surgical dislocation of the hip. Mean age was 38.8 (range 17-56). There were 26 males and 20 females. All patients had Magnetic Resonance Imaging with gadolinium arthrography (MRA) before undergoing open hip surgery where the acetabular cartilage was inspected. Acetabular cartilage delamination on MRA was seen on sagittal images as a linear intra-articular filling defect of low signal intensity >1mm in thickness on T1 weighted images and surrounded by contrast. On MRA all hips had a labral tear confirmed at surgery. At surgery 30 hips had evidence of acetabular cartilage delamination, 4 hips had ulceration and 14 had no articular cartilage damage. The majority of labral tears and cartilage damage were located in the antero-superior quadrant. The sensitivity and specificity of MRA detection of cartilage delamination confirmed at surgery were 97% and 84%, respectively. The positive and negative predictive values of the MRA finding were 90% and 94%, respectively. The presence of the acetabular cartilage delamination represents an early stage of articular cartilage degeneration. When evaluating a young adult with hip pain, labral tears in association with cartilage delamination should be considered. MRA represents an effective diagnostic tool.

Compliance assessed by the Medication Event Monitoring System.

PubMed Central

Olivieri, N F; Matsui, D; Hermann, C; Koren, G

1991-01-01

The accurate assessment of patient compliance is especially crucial in evaluating the efficacy of a new treatment. Because of the problems associated with parenteral desferrioxamine, the development of a safe, effective, and convenient iron chelator is of high priority. The high morbidity and mortality associated with iron overload requires careful evaluation of the ability of any new agent to promote long term effective iron chelation. Patients' compliance with an orally available chelating agent, 1,2,-dimethyl-3-hydroxypyrid-4-one (L1), that has been demonstrated to induce in vivo iron excretion equivalent to that of desferrioxamine during supervised short term administration, was examined. Compliance was assessed in seven patients by patient interview, by daily diaries reviewed monthly with each patient, and with the use of the Medication Event Monitoring System (MEMS) standard pill bottles with microprocessors in the cap that record the timing and frequency of bottle openings. L1 was dispensed in MEMS containers to the patients, who, unaware of their significance, recorded compliance using a daily diary. Overall compliance rate (% of prescribed doses taken) measured by MEMS was 88.7 +/- 6.8%. When 'doubling of doses' was accounted for, significantly poorer compliance with L1 was noted by MEMS (91.7 +/- 7.4%) than by patients' diaries (95.7 +/- 5.2%). There was no significant difference in patient compliance recorded between the first and last 30 day period of drug administration. MEMS can eliminate the confounding variable of erratic patient compliance in the evaluation of a new drug's efficacy. As MEMS cannot distinguish a missed dose from one doubled at the next bottle opening, the use of patient diaries is a useful adjunct to the accurate assessment of compliance and should be combined with the use of MEMS. PMID:1776885

Natural chelating agents for radionuclide decorporation

DOEpatents

Premuzic, E.T.

1985-06-11

This invention relates to the production of metal-binding compounds useful for the therapy of heavy metal poisoning, for biological mining and for decorporation of radionuclides. The present invention deals with an orderly and effective method of producing new therapeutically effective chelating agents. This method uses challenge biosynthesis for the production of chelating agents that are specific for a particular metal. In this approach, the desired chelating agents are prepared from microorganisms challenged by the metal that the chelating agent is designed to detoxify. This challenge induces the formation of specific or highly selective chelating agents. The present invention involves the use of the challenge biosynthetic method to produce new complexing/chelating agents that are therapeutically useful to detoxify uranium, plutonium, thorium and other toxic metals. The Pseudomonas aeruginosa family of organisms is the referred family of microorganisms to be used in the present invention to produce the new chelating agent because this family is known to elaborate strains resistant to toxic metals.

Function of the iron-binding chelator produced by Coriolus versicolor in lignin biodegradation.

PubMed

Wang, Lu; Yan, WenChao; Chen, JiaChuan; Huang, Feng; Gao, PeiJi

2008-03-01

An ultrafiltered low-molecular-weight preparation of chelating compounds was isolated from a wood-containing culture of the white-rot basidiomycete Coriolus versicolor. This preparation could chelate Fe3+ and reduce Fe3+ to Fe2+, demonstrating that the substance may serve as a ferric chelator, oxygen-reducing agent, and redox-cycling molecule, which would include functioning as the electron transport carrier in Fenton reaction. Lignin was treated with the iron-binding chelator and the changes in structure were investigated by 1H-NMR, 13C-NMR, difference spectrum caused by ionization under alkaline conditions and nitrobenzene oxidation. The results indicated that the iron-binding chelator could destroy the beta-O-4 bonds in etherified lignin units and insert phenolic hydroxyl groups. The low-molecular-weight chelator secreted by C. versicolor resulted in new phenolic substructures in the lignin polymer, making it susceptible to attack by laccase or manganese peroxidase. Thus, the synergic action of the iron-binding chelator and the lignocellulolytic enzymes made the substrate more accessible to degradation.

Application of manures to mitigate the harmful effects of electrokinetic remediation of heavy metals on soil microbial properties in polluted soils.

PubMed

Tahmasbian, Iman; Safari Sinegani, Ali Akbar; Nguyen, Thi Thu Nhan; Che, Rongxiao; Phan, Thuc D; Hosseini Bai, Shahla

2017-12-01

Ethylenediaminetetraacetic acid (EDTA) used with electrokinetic (EK) to remediate heavy metal-polluted soils is a toxic chelate for soil microorganisms. Therefore, this study aimed to evaluate the effects of alternative organic chelates to EDTA on improving the microbial properties of a heavy metal-polluted soil subjected to EK. Cow manure extract (CME), poultry manure extract (PME) and EDTA were applied to a lead (Pb) and zinc (Zn)-polluted calcareous soil which were subjected to two electric intensities (1.1 and 3.3 v/cm). Soil carbon pools, microbial activity, microbial abundance (e.g., fungal, actinomycetes and bacterial abundances) and diethylenetriaminepentaacetic acid (DTPA)-extractable Pb and Zn (available forms) were assessed in both cathodic and anodic soils. Applying the EK to soil decreased all the microbial variables in the cathodic and anodic soils in the absence or presence of chelates. Both CME and PME applied with two electric intensities decreased the negative effect of EK on soil microbial variables. The lowest values of soil microbial variables were observed when EK was combined with EDTA. The following order was observed in values of soil microbial variables after treating with EK and chelates: EK + CME or EK + PME > EK > EK + EDTA. The CME and PME could increase the concentrations of available Pb and Zn, although the increase was less than that of EDTA. Overall, despite increasing soil available Pb and Zn, the combination of EK with manures (CME or PME) mitigated the negative effects of using EK on soil microbial properties. This study suggested that the synthetic chelates such as EDTA could be replaced with manures to alleviate the environmental risks of EK application.

Oxidative degradation stability and hydrogen sulfide removal performance of dual-ligand iron chelate of Fe-EDTA/CA.

PubMed

Miao, Xinmei; Ma, Yiwen; Chen, Zezhi; Gong, Huijuan

2017-09-05

Catalytic oxidation desulfurization using chelated iron catalyst is an effective method to remove H 2 S from various gas streams including biogas. However, the ligand of ethylenediaminetetraacetic acid (EDTA), which is usually adopted to prepare chelated iron catalyst, is liable to be oxidative degraded, and leads to the loss of desulfurization performance. In order to improve the degradation stability of the iron chelate, a series of iron chelates composed of two ligands including citric acid (CA) and EDTA were prepared and the oxidative degradation stability as well as desulfurization performance of these chelated iron catalysts were studied. Results show that the iron chelate of Fe-CA is more stable than Fe-EDTA, while for the desulfurization performance, the situation is converse. For the dual-ligand iron chelates of Fe-EDTA/CA, with the increase of mol ratio of CA to EDTA in the iron chelate solution, the oxidative degradation stability increased while the desulfurization performance decreased. The results of this work showed that Fe-EDTA/CA with a mol ratio of CA:EDTA = 1:1 presents a relative high oxidative degradation stability and an acceptable desulfurization performance with over 90% of H 2 S removal efficiency.

Metal-oxo containing polymer nanobeads as potential contrast agents for magnetic resonance imaging

NASA Astrophysics Data System (ADS)

Pablico, Michele Huelar

Magnetic resonance imaging (MRI) has greatly revolutionized the way diseases are detected and treated, as it is a non-invasive imaging modality solely based on the interaction of radiowaves and hydrogen nuclei in the presence of an external magnetic field. It is widely used today for the diagnosis of diseases as it offers an efficient method of mapping structure and function of soft tissues in the body. Most MRI examinations utilize paramagnetic materials known as contrast agents, which enhance the MR signal by decreasing the longitudinal (T1) and transverse (T2) relaxation times of the surrounding water protons in biological systems. This results into increased signal intensity differences thereby allowing better interpretation and analysis of pathological tissues. Contrast agents function by lowering the T1 or lowering the T2, resulting into bright and dark contrasts, respectively. The most common MRI contrast agents that are in clinical use today are gadolinium chelates and superparamagnetic iron oxide nanoparticles, both of which have their own advantages in terms of contrast enhancement properties. In the past few years, however, there has been interest in utilizing metal-containing clusters for MRI contrast enhancement as these materials bridge the gap between the constrained structure and magnetic properties of the gadolinium chelates with the superparamagnetic behavior of the iron oxide nanoparticles. Recently, metallic clusters containing Mn and Fe metal centers have received increased attention mainly because of their potential for high spin states and benign nature. In the quest to further develop novel imaging agents, this research has focused on investigating the use of metal-oxo clusters as potential contrast agents for MRI. The primary goal of this project is to identify clusters that meet the following criteria: high paramagnetic susceptibility, water-soluble, stable, cheap, contain environmentally benign metals, and easily derivatized. This work is also directed at developing metal-oxo containing hybrid materials using first row transition metals with potential catalytic and magnetic properties as well. We report several screened metal-oxo clusters but this study has centered on the mixed-metal oxo cluster, Mn8Fe4O 12(O2CCH3)16(H2O)4 or Mn8Fe4, mainly because it is highly paramagnetic and is soluble and stable in water. The cluster was screened for potential MRI contrast and was found to be a very promising T2 contrast agent with relaxivity values of r1 = 2.3 mM-1s -1 and r2 = 29.5 mM-1s-1. Initial cell studies on two human prostate cancer cell lines, DU-145 and LNCap, reveal that the cluster has low cytotoxicity and may be potentially used in vivo. One key advantage of Mn8Fe4 is its ability to undergo ligand exchange reactions, thus providing a mechanism for grafting to a variety of supports. By substituting the acetate groups on Mn8Fe4 with polymerizable ligands, we are able to form monodisperse magnetic polymer nanobeads (˜70 nm diameter) via the miniemulsion polymerization technique. To render the nanobead suitable for future in vivo experiments, we coated the surface with biocompatible polysaccharide dextran (40 kDa). Interestingly, relaxivity measurements and MRI studies show that encapsulating the Mn8Fe4 core within a polymer matrix decreased T 2 effects resulting in a positive T1 contrast enhancement. The resulting hybrid particles have the potential for further surface functionalization (i.e., therapeutic drugs, targeting moiety, fluorescent probe, etc.) making them a promising tool for biomedicine.

Efficacy of Deferasirox as an Oral Iron Chelator in Paediatric Thalassaemia Patients

PubMed Central

Hishikar, Rajesh; Khandwal, Onkar; Agarwal, Manju; Joshi, Usha; Halwai, Ajay; Maheshwari, Basant; Sheohare, Raka

2017-01-01

Introduction Thalassaemia Major patients require frequent blood transfusion leading to iron overload. Excessive iron gets deposited in vital organs and leads to dysfunction of the heart, liver, anterior pituitary, pancreas, and joints. Our body has limited mechanism to excrete iron, so patients with iron overload and its complications need safe and effective iron chelation therapy. Aim To assess the efficacy of Deferasirox (DFX) as an iron chelator, with specific reference to reduction in serum ferritin level. Materials and Methods This is a prospective; observational study done in 45 multitransfused Thalassaemia Major Children receiving DFX therapy at registered Thalassaemia society Raipur Chhattisgarh. DFX was given in an initial dose of 20 mg/kg/day and according to response increased to a maximum of 40 mg/kg/day. Serum ferritin level was estimated at time of registration and at every three monthly intervals (four times during study period). The primary end point of the study was change in serum ferritin level after 12 months of DFX therapy. Results The mean serum ferritin before DFX therapy of all cases was 3727.02 ng/mL. After 12 months of mean dose of 38 mg/kg/day of DFX, the mean decline in serum ferritin was 1207.11 ng/mL (drop by 32.38%, p-value <0.001). Conclusion DFX monotherapy has a good safety profile and effectively chelates total body iron in Thalassaemia major patients. PMID:28384880

Efficacy of Deferasirox as an Oral Iron Chelator in Paediatric Thalassaemia Patients.

PubMed

Jaiswal, Shikha; Hishikar, Rajesh; Khandwal, Onkar; Agarwal, Manju; Joshi, Usha; Halwai, Ajay; Maheshwari, Basant; Sheohare, Raka

2017-02-01

Thalassaemia Major patients require frequent blood transfusion leading to iron overload. Excessive iron gets deposited in vital organs and leads to dysfunction of the heart, liver, anterior pituitary, pancreas, and joints. Our body has limited mechanism to excrete iron, so patients with iron overload and its complications need safe and effective iron chelation therapy. To assess the efficacy of Deferasirox (DFX) as an iron chelator, with specific reference to reduction in serum ferritin level. This is a prospective; observational study done in 45 multitransfused Thalassaemia Major Children receiving DFX therapy at registered Thalassaemia society Raipur Chhattisgarh. DFX was given in an initial dose of 20 mg/kg/day and according to response increased to a maximum of 40 mg/kg/day. Serum ferritin level was estimated at time of registration and at every three monthly intervals (four times during study period). The primary end point of the study was change in serum ferritin level after 12 months of DFX therapy. The mean serum ferritin before DFX therapy of all cases was 3727.02 ng/mL. After 12 months of mean dose of 38 mg/kg/day of DFX, the mean decline in serum ferritin was 1207.11 ng/mL (drop by 32.38%, p-value <0.001). DFX monotherapy has a good safety profile and effectively chelates total body iron in Thalassaemia major patients.

Synthesis and spectroscopic investigations of hydroxyapatite using a green chelating agent as template

NASA Astrophysics Data System (ADS)

Gopi, D.; Bhuvaneshwari, N.; Indira, J.; Kavitha, L.

2013-03-01

Hydroxyapatite [Ca10(PO4)6(OH)2, HAP] particles have been successfully synthesized by a cost-effective, eco-friendly green template method using natural and commercially available sucrose as a chelating agent. The sucrose used in this method has been extracted from various sources, three from natural and one from commercially available sources are exploited in our study to achieve a controlled crystallinity, particle size as well as uniform morphology. Spectral characterizations involving Fourier transform infrared spectroscopy (FT-IR) for the functional group analysis of sucrose and HAP; carbon-13 nuclear magnetic resonance spectroscopy (13C NMR) for the identification of the carbon atoms in sucrose and in HAP; liquid chromatography/mass spectrometry (LC-MS) for the determination of the hydrolyzed products of sucrose; and X-ray diffraction (XRD) techniques for the phase identification of the HAP particles were performed. The morphology of the HAP particles were assessed thoroughly using a scanning electron microscope (SEM) equipped with energy dispersive X-ray analysis (EDAX). The experimental results indicate that the obtained HAP using the natural sucrose as a chelating agent is of phase pure, with a well defined morphology having discrete particles without any agglomeration than the HAP from commercially available sucrose. Further, the reduced particle size can be achieved from the stem sugarcane extract as the source of the chelating agent.

Synthesis and spectroscopic investigations of hydroxyapatite using a green chelating agent as template.

PubMed

Gopi, D; Bhuvaneshwari, N; Indira, J; Kavitha, L

2013-03-01

Hydroxyapatite [Ca(10)(PO(4))(6)(OH)(2), HAP] particles have been successfully synthesized by a cost-effective, eco-friendly green template method using natural and commercially available sucrose as a chelating agent. The sucrose used in this method has been extracted from various sources, three from natural and one from commercially available sources are exploited in our study to achieve a controlled crystallinity, particle size as well as uniform morphology. Spectral characterizations involving Fourier transform infrared spectroscopy (FT-IR) for the functional group analysis of sucrose and HAP; carbon-13 nuclear magnetic resonance spectroscopy ((13)C NMR) for the identification of the carbon atoms in sucrose and in HAP; liquid chromatography/mass spectrometry (LC-MS) for the determination of the hydrolyzed products of sucrose; and X-ray diffraction (XRD) techniques for the phase identification of the HAP particles were performed. The morphology of the HAP particles were assessed thoroughly using a scanning electron microscope (SEM) equipped with energy dispersive X-ray analysis (EDAX). The experimental results indicate that the obtained HAP using the natural sucrose as a chelating agent is of phase pure, with a well defined morphology having discrete particles without any agglomeration than the HAP from commercially available sucrose. Further, the reduced particle size can be achieved from the stem sugarcane extract as the source of the chelating agent. Copyright © 2012 Elsevier B.V. All rights reserved.

Effects of iron and iron chelation in vitro on mucosal oxidant activity in ulcerative colitis.

PubMed

Millar, A D; Rampton, D S; Blake, D R

2000-09-01

Reactive oxygen species may be pathogenic in ulcerative colitis. Oral iron supplements anecdotally exacerbate inflammatory bowel disease and iron levels are elevated in the inflamed mucosa. Mucosal iron may enhance hydroxyl ion production via Fenton chemistry. Conversely, the iron chelator, desferrioxamine, is reportedly beneficial in Crohn's disease. To assess the in vitro effects of exogenous iron and of iron chelators on the production of reactive oxygen species by colonic biopsies from normal control subjects and patients with ulcerative colitis. Luminol-amplified chemiluminescence was used to measure mucosal reactive oxygen species production both before and after addition in vitro of ferric citrate (100 microM), desferrioxamine (1 mM) and 1,10-phenanthroline (1 mM). Ferric citrate had no effect on the chemiluminescence produced by human colonic mucosa. However, desferrioxamine and phenanthroline reduced chemiluminescence by 47% (n=7, P=0.018) and by 26% (n=10, P=0.005), respectively, in inactive ulcerative colitis, and by 44% (n=9, P=0. 008) and 42% (n=11, P=0.006) in active disease. The lack of effect of ferric citrate suggests that sufficient free iron is already present in inflamed biopsies to drive the Fenton reaction maximally. The effects of desferrioxamine and 1,10-phenanthroline on the chemiluminescence of biopsies from patients with ulcerative colitis suggest that a clinical trial of topical iron chelation in active disease is indicated.

Soft chelating irrigation protocol optimizes bonding quality of Resilon/Epiphany root fillings.

PubMed

De-Deus, Gustavo; Namen, Fátima; Galan, João; Zehnder, Matthias

2008-06-01

This study was designed to test the impact of either a strong (MTAD) or a soft (1-hydroxyethylidene-1, 1-bisphosphonate [HEPB]) chelating solution on the bond strength of Resilon/Epiphany root fillings. Both 17% EDTA and the omission of a chelator in the irrigation protocol were used as reference treatments. Forty extracted human upper lateral incisors were prepared using different irrigation protocols (n = 10): G1: NaOCl, G2: NaOCl + 17% EDTA, G3: NaOCl + BioPure MTAD (Dentsply/Tulsa, Tulsa, OK), and G4: NaOCl + 18% HEPB. The teeth were obturated and then prepared for micropush-out assessment using root slices of 1 mm thickness. Loading was performed on a universal testing machine at a speed of 0.5 mm/min. One-way analysis of variance and Tukey multiple comparisons were used to compare the results among the experimental groups. EDTA- and MTAD-treated samples revealed intermediate bond strength (0.3-3.6 MPa). The lowest bond strengths were achieved in NaOCl-treated samples (0.3-1.2 MPa, p < 0.05). The highest bond strength was reached in the HEBP-treated samples (3.1-6.1 MPa, p < 0.05). Under the present in vitro conditions, the soft chelating irrigation protocol (18% HEBP) optimized the bonding quality of Resilon/Epiphany (Resilon Research LLC, Madison, CT) root fillings.

A new approach to isolating siderophore-producing actinobacteria.

PubMed

Nakouti, I; Sihanonth, P; Hobbs, G

2012-07-01

This study was conducted to investigate the application of 2,2'-dipyridyl as a new approach to isolating siderophore-producing actinobacteria. Isolation of actinobacteria from soil was conducted by a soil dilution plate technique using starch-casein agar. Iron starvation was fostered by the incorporation of the iron chelator 2,2'-dipyridyl in the isolation medium. Pretreatment of the samples at an elevated temperature (40°C) ensured that the majority of nonsporulating bacteria were excluded. The survivors of this treatment were largely actinobacteria. Of the viable cultures grown in the presence of 2,2'-dipyridyl, more than 78-88% (average of three separate studies) were reported to produce siderophore-like compounds compared to 13-18% (average of three separate studies) when grown on the basic media in the absence of the chelating agent. The most prolific producers as assessed by the chrome azurol sulphate (CAS) assay were further characterized and found to belong to the genus Streptomyces. Selective pressure using 2,2'-dipyridyl as an iron-chelating agent in starch-casein media increased the isolation of siderophore-producing actinobacteria compared to the unamended medium. The study described represents a new approach to the isolation of siderophore-producing actinobacteria using a novel procedure that places a selection on cell population based upon the incorporation of a chelating agent in the medium. © 2012 The Authors. Letters in Applied Microbiology © 2012 The Society for Applied Microbiology.

Effects of exposure to gadolinium on the development of geographically and phylogenetically distant sea urchins species.

PubMed

Martino, Chiara; Bonaventura, Rosa; Byrne, Maria; Roccheri, Maria; Matranga, Valeria

2017-07-01

Gadolinium (Gd), a metal of the lanthanide series used as contrast agent for magnetic resonance imaging, is released into the aquatic environment. We investigated the effects of Gd on the development of four sea urchin species: two from Europe, Paracentrotus lividus and Arbacia lixula, and two from Australia, Heliocidaris tuberculata and Centrostephanus rodgersii. Exposure to Gd from fertilization resulted in inhibition or alteration of skeleton growth in the plutei. The similar morphological response to Gd in the four species indicates a similar mechanism underlying abnormal skeletogenesis. Sensitivity to Gd greatly varied, with the EC50 ranging from 56 nM to 132 μM across the four species. These different sensitivities highlight the importance of testing toxicity in several species for risk assessment. The strong negative effects of Gd on calcification in plutei, together with the plethora of marine species that have calcifying larvae, indicates that Gd pollution is urgent issue that needs to be addressed. Copyright © 2016 Elsevier Ltd. All rights reserved.

Macrocyclic bifunctional chelating agents

DOEpatents

Meares, Claude F.; DeNardo, Sally J.; Cole, William C.; Mol, Min K.

1987-01-01

A copper chelate conjugate which is stable in human serum. The conjugate includes the copper chelate of a cyclic tetraaza di-, tri-, or tetra-acetic acid, a linker attached at one linker end to a ring carbon of the chelate, and a biomolecule joined at the other end of the linker. The conjugate, or the linker-copper chelate compound used in forming the conjugate, are designed for use in diagnostic and therapeutic applications which involve Cu(II) localization via the systemic route.

INFLUENCE OF IRON CHELATION ON R1 AND R2 CALIBRATION CURVES IN GERBIL LIVER AND HEART

PubMed Central

Wood, John C.; Aguilar, Michelle; Otto-Duessel, Maya; Nick, Hanspeter; Nelson, Marvin D.; Moats, Rex

2008-01-01

MRI is gaining increasing importance for the noninvasive quantification of organ iron burden. Since transverse relaxation rates depend on iron distribution as well as iron concentration, physiologic and pharmacologic processes that alter iron distribution could change MRI calibration curves. This paper compares the effect of three iron chelators, deferoxamine, deferiprone, and deferasirox on R1 and R2 calibration curves according to two iron loading and chelation strategies. 33 Mongolian gerbils underwent iron loading (iron dextran 500 mg/kg/wk) for 3 weeks followed by 4 weeks of chelation. An additional 56 animals received less aggressive loading (200 mg/kg/week) for 10 weeks, followed by 12 weeks of chelation. R1 and R2 calibration curves were compared to results from 23 iron-loaded animals that had not received chelation. Acute iron loading and chelation biased R1 and R2 from the unchelated reference calibration curves but chelator-specific changes were not observed, suggesting physiologic rather than pharmacologic differences in iron distribution. Long term chelation deferiprone treatment increased liver R1 50% (p<0.01), while long term deferasirox lowered liver R2 30.9% (p<0.0001). The relationship between R1 and R2 and organ iron concentration may depend upon the acuity of iron loading and unloading as well as the iron chelator administered. PMID:18581418

Fe(III)-EDDHA and -EDDHMA sorption on Ca-montmorillonite, ferrihydrite, and peat.

PubMed

Hernández-Apaolaza, L; Lucena, J J

2001-11-01

The effectiveness of Fe chelates as Fe sources and carriers in soil can be severely limited by the adsorption of Fe chelates or chelating agents in the solid phase. To study this phenomenon, well-characterized peat, Ca-montmorillonite, and ferrihydrite were used as model compounds, and the adsorption of Fe-EDDHA and Fe-EDDHMA chelates were studied. Sorption isotherms for the meso and racemic isomers of these chelates on the soil materials are described. The variability of sorption with pH in peat and ferrihydrite was also determined because both have variable surface charge at different pH values. In montmorillonite, at low concentrations, the retention of Fe from the Fe-EDDHMA chelate is greater than the one of the Fe-EDDHA chelate. As well as the concentration increased, the inverse situation occurs. The behavior of both meso and racemic isomers of chelates in contact with Ca-montmorillonite is similar. The Fe-meso-EDDHA isomer was highly adsorbed on ferrihydrite, but the racemic isomer is not significantly retained by this oxide. For Fe-EDDHMA isomers, the racemic isomer was more retained by the oxide, but a small sorption of the racemic isomer was also observed. Results suggest that Fe-EDDHA chelates were more retained in peat than Fe-EDDHMA chelates. The most retained isomer of Fe-EDDHA was the meso isomer. For Fe-EDDHMA, the adsorption was very low for both racemic and meso isomers.

Chelation in Metal Intoxication

PubMed Central

Flora, Swaran J.S.; Pachauri, Vidhu

2010-01-01

Chelation therapy is the preferred medical treatment for reducing the toxic effects of metals. Chelating agents are capable of binding to toxic metal ions to form complex structures which are easily excreted from the body removing them from intracellular or extracellular spaces. 2,3-Dimercaprol has long been the mainstay of chelation therapy for lead or arsenic poisoning, however its serious side effects have led researchers to develop less toxic analogues. Hydrophilic chelators like meso-2,3-dimercaptosuccinic acid effectively promote renal metal excretion, but their ability to access intracellular metals is weak. Newer strategies to address these drawbacks like combination therapy (use of structurally different chelating agents) or co-administration of antioxidants have been reported recently. In this review we provide an update of the existing chelating agents and the various strategies available for the treatment of heavy metals and metalloid intoxications. PMID:20717537

Type-II domains in ferroelectric gadolinium molybdate (in German)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bohm, J.; Kuersten, H.D.

Etching (001)-faces of gadolinium molybdate (GMO) reveals new kinds of domains. They are created by a translation, that leaves the spontaneous polarization and the transition parameter invariant. The translation vector is a part of a lattice vector, similar to stacking faults. (auth)

[Rapid imaging in orbito-ocular pathology. Contribution of gadolinium].

PubMed

Pigeau, I; Legeais, J M; D'Hermies, F; Fayet, B; Leport, M; Abenhaim, A; Guinet, C; Levy, C; Renard, G; Vadrot, D

1990-01-01

To evaluate Gradient-Echo Imaging (GEI) in orbito-ocular pathology, 15 volunteers and 34 patients (40 lesions) were examined with GEA T1 and GEA T2 (0.5 T). Results were compared with SE T1 in all cases, with SE T2 in 20 cases and with other imaging modalities (CT). 30 patients were examined before and after injection of gadolinium. Final diagnosis was obtained by surgery or biopsy in 24 cases or by combined results of imaging and clinical findings in 16 cases. Compared with SE, GEA demonstrated a better visualisation of optic nerve, orbital muscles, choroidal-retinal layer, lens capsule and episclera and a better detection of small lesions. It is very helpful for characterisation of lesions containing hemorrhages or paramagnetic components (melanine, gadolinium) or of vascular nature (angioma). Gadolinium was useful for detection of small lesions or characterisation of a few lesions. Thus GEA seems to be an efficient method for the evaluation of orbito-ocular pathology.

Efficacy and Safety of Combined Oral Chelation With Deferiprone and Deferasirox in Children With β-Thalassemia Major: An Experience From North India.

PubMed

Parakh, Nupur; Chandra, Jagdish; Sharma, Sunita; Dhingra, Bhavna; Jain, Rajesh; Mahto, DeoNath

2017-04-01

A combination of desferrioxamine with either deferiprone (DFP) or deferasirox (DFX) for patients with β-thalassemia major who do not achieve negative iron balance with monotherapy has been studied widely. However, poor compliance resulting from the need for parentral administration of desferrioxamine and its cost necessicitates combining 2 oral chelators. A prospective study was conducted in patients with transfusion-dependent β-thalassemia major in a tertiary care center over 2 years. Patients on either DFP or DFX who were not improving on monotherapy over a long period and persistently maintaining serum ferritin >2500 µg/L were enrolled. Efficacy was assessed by serum ferritin levels assessed at 12 months and 2 years. Complete blood counts and liver and kidney function tests were monitored to assess the safety of the combination of drugs. In total, 33 patients with a mean age of 12.67 years (7.5 to 17.5 y) and a mean ferritin of 4835.2394±1443.85 µg/L formed the study cohort.In total, 28 patients completed the 1-year study period; and 12 patients completed 2 years. Mean serum ferritin reduction at 1 and 2 years was 34.99%±18.13% (range, -34.36% to 56.17%) and 44.67%±13.78% (range, 22.17% to 62.74%), respectively. The combination therapy was well tolerated. Combined oral chelation with DFP and DFX has better efficacy than either drug used alone. The combination of drugs was well tolerated and no new adverse effects were observed.

Impact of fingolimod therapy on magnetic resonance imaging outcomes in patients with multiple sclerosis.

PubMed

Radue, Ernst-Wilhelm; O'Connor, Paul; Polman, Chris H; Hohlfeld, Reinhard; Calabresi, Peter; Selmaj, Krystof; Mueller-Lenke, Nicole; Agoropoulou, Catherine; Holdbrook, Frederick; de Vera, Ana; Zhang-Auberson, Lixin; Francis, Gordon; Burtin, Pascale; Kappos, Ludwig

2012-10-01

To assess the impact of fingolimod (FTY720) therapy on magnetic resonance imaging measures of inflammatory activity and tissue damage in patients participating in a 2-year, placebo-controlled, phase 3 study. Patients with active relapsing-remitting multiple sclerosis were randomized to receive fingolimod, 0.5 mg; fingolimod, 1.25 mg; or placebo for 2 years. Standardized magnetic resonance imaging scans were obtained at months 0, 6, 12, and 24 and centrally evaluated for number and volume of T1 gadolinium-enhancing, T2 hyperintense, and T1 hypointense lesions and for percentage of brain volume change. Findings were compared across subgroups by treatment and baseline characteristics. Worldwide, multicenter clinical trial. Patients were part of the fingolimod FTY720 Research Evaluating Effects of Daily Oral Therapy in Multiple Sclerosis (FREEDOMS) clinical trial for relapsing-remitting multiple sclerosis (N=1272). We measured the effect of therapy on acute inflammatory activity, burden of disease, and irreversible loss of brain volume. Fingolimod therapy resulted in rapid and sustained reductions in inflammatory lesion activity as assessed by gadolinium-enhancing and new/newly enlarged T2 lesions after 6, 12, and 24 months of therapy (P.001, all comparisons vs placebo). Changes in T2 hyperintense and T1 hypointense lesion volume also significantly favored fingolimod (P.05, all comparisons). Fingolimod, 0.5 mg (licensed dose), significantly reduced brain volume loss during months 0 to 6, 0 to 12, 12 to 24, and 0 to 24 (P.05, all comparisons) vs placebo, and subgroup analyses confirmed these effects over 2 years irrespective of the presence/absence of gadolinium-enhancing lesions, T2 lesion load, previous treatment status, or level of disability. These results, coupled with the significant reductions in relapse rates and disability progression reported previously, support the positive impact on long-term disease evolution. clinicaltrials.gov Identifier: NCT00289978

Contrast-enhanced magnetic resonance angiography: first-pass arterial enhancement as a function of gadolinium-chelate concentration, and the saline chaser volume and injection rate.

PubMed

Husarik, Daniela B; Bashir, Mustafa R; Weber, Paul W; Nichols, Eli B; Howle, Laurens E; Merkle, Elmar M; Nelson, Rendon C

2012-02-01

To evaluate the effect of the contrast medium (CM) concentration and the saline chaser volume and injection rate on first-pass aortic enhancement characteristics in contrast-enhanced magnetic resonance angiography using a physiologic flow phantom. Imaging was performed on a 3.0-T magnetic resonance system (MAGNETOM Trio, Siemens Healthcare Solutions, Inc, Erlangen, Germany) using a 2-dimensional fast low angle shot T1-weighted sequence (repetition time, 500 milliseconds; echo time, 1.23 milliseconds; flip angle, 8 degrees; 1 frame/s × 60 seconds). The following CM concentrations injected at 2 mL/s were used with 3 different contrast agents (gadolinium [Gd]-BOPTA, Gd-HP-DO3A, Gd-DTPA): 20 mL of undiluted CM (100%) and 80%, 40%, 20%, 10%, 5%, and 2.5% of the full amount, all diluted in saline to a volume of 20 mL to ensure equal bolus volume. The CM was followed by saline chasers of 20 to 60 mL injected at 2 mL/s and 6 mL/s. Aortic signal intensity (SI) was measured, and normalized SI versus time (SI/Tn) curves were generated. The maximal SI (SI(max)), bolus length, and areas under the SI/Tn curve were calculated. Decreasing the CM concentration from 100% to 40% resulted in a decrease of SI(max) to 86.1% (mean). Further decreasing the CM concentration to 2.5% decreased SI(max) to 5.1% (mean). Altering the saline chaser volume had no significant effect on SI(max). Increasing the saline chaser injection rate had little effect (mean increase, 2.2%) on SI(max) when using ≥40% of CM. There was a larger effect (mean increase, 19.6%) when ≤20% of CM were used. Bolus time length was significantly shorter (P < 0.001), and area under the SI/T(n) curve was significantly smaller (P < 0.01) for the CM protocols followed by a saline chaser injected at 6 mL/s compared with a saline chaser injected at 2 mL/s. With 40% of CM and a fast saline chaser, SImax close to that with undiluted CM can be achieved. An increased saline chaser injection rate has a more pronounced effect on aortic enhancement characteristics at lower CM concentrations than at higher CM concentrations.

Deep learning enables reduced gadolinium dose for contrast-enhanced brain MRI.

PubMed

Gong, Enhao; Pauly, John M; Wintermark, Max; Zaharchuk, Greg

2018-02-13

There are concerns over gadolinium deposition from gadolinium-based contrast agents (GBCA) administration. To reduce gadolinium dose in contrast-enhanced brain MRI using a deep learning method. Retrospective, crossover. Sixty patients receiving clinically indicated contrast-enhanced brain MRI. 3D T 1 -weighted inversion-recovery prepped fast-spoiled-gradient-echo (IR-FSPGR) imaging was acquired at both 1.5T and 3T. In 60 brain MRI exams, the IR-FSPGR sequence was obtained under three conditions: precontrast, postcontrast images with 10% low-dose (0.01mmol/kg) and 100% full-dose (0.1 mmol/kg) of gadobenate dimeglumine. We trained a deep learning model using the first 10 cases (with mixed indications) to approximate full-dose images from the precontrast and low-dose images. Synthesized full-dose images were created using the trained model in two test sets: 20 patients with mixed indications and 30 patients with glioma. For both test sets, low-dose, true full-dose, and the synthesized full-dose postcontrast image sets were compared quantitatively using peak-signal-to-noise-ratios (PSNR) and structural-similarity-index (SSIM). For the test set comprised of 20 patients with mixed indications, two neuroradiologists scored blindly and independently for the three postcontrast image sets, evaluating image quality, motion-artifact suppression, and contrast enhancement compared with precontrast images. Results were assessed using paired t-tests and noninferiority tests. The proposed deep learning method yielded significant (n = 50, P < 0.001) improvements over the low-dose images (>5 dB PSNR gains and >11.0% SSIM). Ratings on image quality (n = 20, P = 0.003) and contrast enhancement (n = 20, P < 0.001) were significantly increased. Compared to true full-dose images, the synthesized full-dose images have a slight but not significant reduction in image quality (n = 20, P = 0.083) and contrast enhancement (n = 20, P = 0.068). Slightly better (n = 20, P = 0.039) motion-artifact suppression was noted in the synthesized images. The noninferiority test rejects the inferiority of the synthesized to true full-dose images for image quality (95% CI: -14-9%), artifacts suppression (95% CI: -5-20%), and contrast enhancement (95% CI: -13-6%). With the proposed deep learning method, gadolinium dose can be reduced 10-fold while preserving contrast information and avoiding significant image quality degradation. 3 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2018. © 2018 International Society for Magnetic Resonance in Medicine.

Bi-atrial fibrosis detected using three-dimensional late gadolinium enhancement magnetic resonance imaging in a patient with cardiac sarcoidosis.

PubMed

Spence, Stewart; Pena, Elena; Thornhill, Rebecca E; Nery, Pablo B; Birnie, David H

2018-05-01

Presented is the case of a 62-year old male with a history of sarcoidosis and sinus node dysfunction, who underwent late gadolinium enhancement magnetic resonance imaging, which demonstrated left ventricular hyperenhancement and bi-atrial fibrosis.

Technical Basis for Peak Reactivity Burnup Credit for BWR Spent Nuclear Fuel in Storage and Transportation Systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marshall, William BJ J; Ade, Brian J; Bowman, Stephen M

2015-01-01

Oak Ridge National Laboratory and the United States Nuclear Regulatory Commission have initiated a multiyear project to investigate application of burnup credit for boiling-water reactor (BWR) fuel in storage and transportation casks. This project includes two phases. The first phase (1) investigates applicability of peak reactivity methods currently used in spent fuel pools (SFPs) to storage and transportation systems and (2) evaluates validation of both reactivity (k eff) calculations and burnup credit nuclide concentrations within these methods. The second phase will focus on extending burnup credit beyond peak reactivity. This paper documents the first phase, including an analysis of latticemore » design parameters and depletion effects, as well as both validation components. Initial efforts related to extended burnup credit are discussed in a companion paper. Peak reactivity analyses have been used in criticality analyses for licensing of BWR fuel in SFPs over the last 20 years. These analyses typically combine credit for the gadolinium burnable absorber present in the fuel with a modest amount of burnup credit. Gadolinium burnable absorbers are used in BWR assemblies to control core reactivity. The burnable absorber significantly reduces assembly reactivity at beginning of life, potentially leading to significant increases in assembly reactivity for burnups less than 15–20 GWd/MTU. The reactivity of each fuel lattice is dependent on gadolinium loading. The number of gadolinium-bearing fuel pins lowers initial lattice reactivity, but it has a small impact on the burnup and reactivity of the peak. The gadolinium concentration in each pin has a small impact on initial lattice reactivity but a significant effect on the reactivity of the peak and the burnup at which the peak occurs. The importance of the lattice parameters and depletion conditions are primarily determined by their impact on the gadolinium depletion. Criticality code validation for BWR burnup credit at peak reactivity requires a different set of experiments than for pressurized-water reactor burnup credit analysis because of differences in actinide compositions, presence of residual gadolinium absorber, and lower fission product concentrations. A survey of available critical experiments is presented along with a sample criticality code validation and determination of undercoverage penalties for some nuclides. The validation of depleted fuel compositions at peak reactivity presents many challenges which largely result from a lack of radiochemical assay data applicable to BWR fuel in this burnup range. In addition, none of the existing low burnup measurement data include residual gadolinium measurements. An example bias and uncertainty associated with validation of actinide-only fuel compositions is presented.« less

Chelators whose affinity for calcium is decreased by illumination

NASA Technical Reports Server (NTRS)

Tsien, Roger Y. (Inventor); Grynkiewicz, Grzegorz (Inventor); Minta, Akwasi (Inventor)

1987-01-01

The present invention discloses a group of calcium chelating compounds which have a descreased affinity for calcium following illumination. These new compounds contain a photolabile nitrobenzyl derivative coupled to a tetracarboxylate Ca.sup.2+ chelating parent compound having the octacoordinate chelating groups characteristic of EGTA or BAPTA. In a first form, the new compounds are comprised of a BAPTA-like chelator coupled to a single 2-nitrobenzyl derivative, which in turn is a photochemical precursor of a 2-nitrosobenzophenone. In a second form, the new compounds are comprised of a BAPTA-like chelator coupled to two 2-nitrobenzyl derivatives, themselves photochemical prcursors of the related 2-nitrosobenzophenones. The present invention also discloses a novel method for preparing 1-hydroxy- or 1-alkoxy-1-(2-nitroaryl)-1-aryl methanes. Methanes of this type are critical to the preparation of, or actually constitute, the photolabile Ca.sup.2+ chelating compounds disclosed and claimed herein.

Corrosion resistance of 0Kh18N10T steel in gadolinium nitrate solutions in the liquid regulation of the reactivity of nuclear reactors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ganzha, V.D.; Konoplev, K.A.; Mashchetov, V.P.

1986-03-01

This study was carried out in connection with the preparation of the design for the PIK research reactor. The corrosion resistance of 0Kh18N10T steel in gadolinium nitrate solutions was tested in laboratory, ampule, and loop corrosion tests. At all stages of the tests, the authors investigated the effect produced on the corrosion processes by factors related to the technology of preparation of the equipment (mechanical working of the surfaces, welding, sensitizing, annealing, stressed state of the material, cracks, etc.). Ampule tests were conducted in order to determine the effect produced by reactor radiation and shutdown regimes on the corrosion resistancemore » of the steel. Special ampules made of 0Kh18N10T steel were filled with gadolinium nitrate solutions of various concentrations, sealed, and irradiated for a long period in the core of the VVR-M reactor at a temperature of 20-50 degrees C. The results of the tests are shown. The investigations showed that the corrosion of 0Kh18N10T steel in solutions of gadolinium nitrate is uniform, regardless of the state of the surface, the concentration of gadolinium nitrate, the duration of the tests, the action of the reactor radiation under static and dynamic conditions, and the presence of mechanical stresses.« less

Antimicrobial Properties of Copper Nanoparticles and Amino Acid Chelated Copper Nanoparticles Produced by Using a Soya Extract.

PubMed

DeAlba-Montero, I; Guajardo-Pacheco, Jesús; Morales-Sánchez, Elpidio; Araujo-Martínez, Rene; Loredo-Becerra, G M; Martínez-Castañón, Gabriel-Alejandro; Ruiz, Facundo; Compeán Jasso, M E

2017-01-01

This paper reports a comparison of the antibacterial properties of copper-amino acids chelates and copper nanoparticles against Escherichia coli , Staphylococcus aureus , and Enterococcus faecalis . These copper-amino acids chelates were synthesized by using a soybean aqueous extract and copper nanoparticles were produced using as a starting material the copper-amino acids chelates species. The antibacterial activity of the samples was evaluated by using the standard microdilution method (CLSI M100-S25 January 2015). In the antibacterial activity assays copper ions and copper-EDTA chelates were included as references, so that copper-amino acids chelates can be particularly suitable for acting as an antibacterial agent, so they are excellent candidates for specific applications. Additionally, to confirm the antimicrobial mechanism on bacterial cells, MTT assay (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) was carried out. A significant enhanced antimicrobial activity and a specific strain were found for copper chelates over E. faecalis . Its results would eventually lead to better utilization of copper-amino acids chelate for specific application where copper nanoparticles can be not used.

Antimicrobial Properties of Copper Nanoparticles and Amino Acid Chelated Copper Nanoparticles Produced by Using a Soya Extract

PubMed Central

DeAlba-Montero, I.; Morales-Sánchez, Elpidio; Araujo-Martínez, Rene

2017-01-01

This paper reports a comparison of the antibacterial properties of copper-amino acids chelates and copper nanoparticles against Escherichia coli, Staphylococcus aureus, and Enterococcus faecalis. These copper-amino acids chelates were synthesized by using a soybean aqueous extract and copper nanoparticles were produced using as a starting material the copper-amino acids chelates species. The antibacterial activity of the samples was evaluated by using the standard microdilution method (CLSI M100-S25 January 2015). In the antibacterial activity assays copper ions and copper-EDTA chelates were included as references, so that copper-amino acids chelates can be particularly suitable for acting as an antibacterial agent, so they are excellent candidates for specific applications. Additionally, to confirm the antimicrobial mechanism on bacterial cells, MTT assay (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) was carried out. A significant enhanced antimicrobial activity and a specific strain were found for copper chelates over E. faecalis. Its results would eventually lead to better utilization of copper-amino acids chelate for specific application where copper nanoparticles can be not used. PMID:28286459

Characterization of commercial iron chelates and their behavior in an alkaline and calcareous soil.

PubMed

Cantera, Rodrigo G; Zamarreño, Angel M; García-Mina, José M

2002-12-18

Iron deficiency is a common problem for many plants grown in alkaline and calcareous soils. To correct this problem, iron is supplied to plants as chelates. Several iron chelates are sold under diverse trademarks with different characteristics. This work evaluated 18 commercial products containing the most representative chelated iron sources used in agricultural practice in Spain when the study was done, namely the ferric chelates of EDDHA, EDDHMA, EDDCHA, EDDHSA, EDTA, and DTPA. The chelates were comprehensively characterized and quantitated by several techniques, including several chromatographic methods. Iron and chelate dynamics in soil were also studied in a model alkaline and calcareous soil. Results indicate that, in this model soil, among the different iron compounds studied only FeEDDHA and analogues have the capacity to maintain soluble iron in soil solution over time. These results are in agreement with general experience under field conditions. Furthermore, among the different ortho-ortho isomers of FeEDDHA's, FeEDDHSA and FeEDDCHA showed greater capacity than FeEDDHA and FeEDDHMA to maintain the chelated iron in soil solution over time.

Luminescent Properties of Eu(III) Chelates on Metal Nanorods

PubMed Central

Zhang, Jian; Fu, Yi; Ray, Krishanu; Wang, Yuan; Lakowicz, Joseph. R.

2013-01-01

In this article, we report the change of optical properties for europium chelates on silver nanorods by near-field interactions. The silver rods were fabricated in a seed-growth method followed by depositing thin layers of silica on the surfaces. The europium chelates were physically absorbed in the silica layers on the silver rods. The silver rods were observed to exhibit two plasmon absorption bands from longitudinal and transverse directions, respectively, centered at 394 and 675 nm, close to absorption and emission bands from the Eu(III) chelates. As a result, the immobilized Eu(III) chelates on the silver rods should have strong interactions with the silver nanorods and lead to greatly improved optical properties. The Eu–Ag rod complexes were observed to have enhanced emission intensity up to 240-fold in comparison with the Eu(III) chelates in the metal-free silica templates. This enhancement is much larger than the value for the Eu(III) chelates on the gold rods or silver spheres indicating the presence of stronger interactions for the Eu(III) chelates with the silver rods. The interactions of Eu(III) chelates with the silver rods were also proven by extremely reduced lifetime. Moreover, the Eu–Ag rod complexes exhibited a polarized emission, which was also due to strong interactions of the Eu(III) chelates with the silver rods. All of these features may promise that the Eu(III)–Ag rod complexes have great potential for use as fluorescence imaging agents in biological assays. PMID:24363816

Photo-Curable Metal-Chelating Coatings Offer a Scalable Approach to Production of Antioxidant Active Packaging.

PubMed

Lin, Zhuangsheng; Goddard, Julie

2018-02-01

Synthetic metal chelators (for example, ethylenediaminetetraacetic acid, EDTA) are widely used as additives to control trace transition metal induced oxidation in consumer products. To enable removal of synthetic chelators in response to increasing consumer demand for clean label products, metal-chelating active food packaging technologies have been developed with demonstrated antioxidant efficacy in simulated food systems. However, prior work in fabrication of metal-chelating materials leveraged batch chemical reactions to tether metal-chelating ligands, a process with limited industrial translatability for large-scale fabrication. To improve the industrial translatability, we have designed a 2-step laminated photo-grafting process to introduce metal chelating functionality onto common polymeric packaging materials. Iminodiacetic acid (IDA) functionalized materials were fabricated by photo-grafting poly(acrylic acid) onto polypropylene (PP) films, followed by a second photo-grafting process to graft-polymerize an IDA functionalized vinyl monomer (GMA-IDA). The photo-grafting was conducted under atmospheric conditions and was completed in 2 min. The resulting IDA functionalized metal-chelating material was able to chelate iron and copper, and showed antioxidant efficacy against ascorbic acid degradation, supporting its potential to be used synergistically with natural antioxidants for preservation of food and beverage products. The 2-step photo-grafting process improves the throughput of active packaging coatings, enabling potential roll-to-roll fabrication of metal-chelating active packaging materials for antioxidant food packaging applications. To address consumer and retail demands for "clean label" foods and beverages without a corresponding loss in product quality and shelf life, producers are seeking next generation technologies such as active packaging. In this work, we will report the synthesis of metal-chelating active packaging films, which enable removal of the synthetic additive, ethylenediamine tetraacetic acid. The new synthesis technique improves the throughput of metal-chelating active packaging coatings, enabling potential roll-to-roll fabrication of the materials for antioxidant food packaging applications. © 2018 Institute of Food Technologists®.

Gadolinium: Central Metal of the Lanthanoids

ERIC Educational Resources Information Center

Laing, Michael

2009-01-01

The physical and chemical properties of gadolinium are compared with those of the other lanthanoids. Some properties are intermediate between those of lanthanum and lutetium; some between those of barium and hafnium; and others (unexpectedly) between those of ytterbium and lutetium. Both the remarkably high molar heat capacity of the metal and the…

N- vs. C-Domain Selectivity of Catalytic Inactivation of Human Angiotensin Converting Enzyme by Lisinopril-Coupled Transition Metal Chelates

PubMed Central

Hocharoen, Lalintip; Joyner, Jeff C.; Cowan, J. A.

2014-01-01

The N- and C-terminal domains of human somatic Angiotensin I Converting Enzyme (sACE-1) demonstrate distinct physiological functions, with resulting interest in the development of domain-selective inhibitors for specific therapeutic applications. Herein, the activity of lisinopril-coupled transition metal chelates were tested for both reversible binding and irreversible catalytic inactivation of sACE-1. C/N domain binding selectivity ratios ranged from 1 to 350, while rates of irreversible catalytic inactivation of the N- and C-domains were found to be significantly greater for the N-domain, suggesting a more optimal orientation of the M-chelate-lisinopril complexes within the active site of the N-domain of sACE-1. Finally, the combined effect of binding selectivity and inactivation selectivity was assessed for each catalyst (double-filter selectivity factors), and several catalysts were found to cause domain-selective catalytic inactivation. The results of this study demonstrate the ability to optimize the target selectivity of catalytic metallopeptides through both binding and orientation factors (double-filter effect). PMID:24228790

N- versus C-domain selectivity of catalytic inactivation of human angiotensin converting enzyme by lisinopril-coupled transition metal chelates.

PubMed

Hocharoen, Lalintip; Joyner, Jeff C; Cowan, J A

2013-12-27

The N- and C-terminal domains of human somatic angiotensin I converting enzyme (sACE-1) demonstrate distinct physiological functions, with resulting interest in the development of domain-selective inhibitors for specific therapeutic applications. Herein, the activity of lisinopril-coupled transition metal chelates was tested for both reversible binding and irreversible catalytic inactivation of each domain of sACE-1. C/N domain binding selectivity ratios ranged from 1 to 350, while rates of irreversible catalytic inactivation of the N- and C-domains were found to be significantly greater for the N-domain, suggesting a more optimal orientation of M-chelate-lisinopril complexes within the active site of the N-domain of sACE-1. Finally, the combined effect of binding selectivity and inactivation selectivity was assessed for each catalyst (double-filter selectivity factors), and several catalysts were found to cause domain-selective catalytic inactivation. The results of this study demonstrate the ability to optimize the target selectivity of catalytic metallopeptides through both binding and catalytic factors (double-filter effect).

The role of magnetic resonance imaging in the evaluation of transfusional iron overload in myelodysplastic syndromes

PubMed Central

Petrou, Emmanouil; Mavrogeni, Sophie; Karali, Vasiliki; Kolovou, Genovefa; Kyrtsonis, Marie-Christine; Sfikakis, Petros P.; Panayiotidis, Panayiotis

2015-01-01

Myelodysplastic syndromes represent a group of heterogeneous hematopoietic neoplasms derived from an abnormal multipotent progenitor cell, characterized by a hyperproliferative bone marrow, dysplasia of the cellular hemopoietic elements and ineffective erythropoiesis. Anemia is a common finding in myelodysplastic syndrome patients, and blood transfusions are the only therapeutic option in approximately 40% of cases. The most serious side effect of regular blood transfusion is iron overload. Currently, cardiovascular magnetic resonance using T2 is routinely used to identify patients with myocardial iron overload and to guide chelation therapy, tailored to prevent iron toxicity in the heart. This is a major validated non-invasive measure of myocardial iron overloading and is superior to surrogates such as serum ferritin, liver iron, ventricular ejection fraction and tissue Doppler parameters. The indication for iron chelation therapy in myelodysplastic syndrome patients is currently controversial. However, cardiovascular magnetic resonance may offer an excellent non-invasive, diagnostic tool for iron overload assessment in myelodysplastic syndromes. Further studies are needed to establish the precise indications of chelation therapy and the clinical implications of this treatment on survival in myelodysplastic syndromes. PMID:26190429

Transglutaminase-mediated conjugation and nitride-technetium-99m labelling of a bis(thiosemicarbazone) bifunctional chelator.

PubMed

Salvarese, Nicola; Spolaore, Barbara; Marangoni, Selena; Pasin, Anna; Galenda, Alessandro; Tamburini, Sergio; Cicoria, Gianfranco; Refosco, Fiorenzo; Bolzati, Cristina

2018-06-01

An assessment study involving the use of the transglutaminase (TGase) conjugation method and the nitride-technetium-99m labelling on a bis(thiosemicarbazone) (BTS) bifunctional chelating agent is presented. The previously described chelator diacetyl-2-(N 4 -methyl-3-thiosemicarbazone)-3-(N 4 -amino-3-thiosemicarbazone), H 2 ATSM/A, has been functionalized with 6-aminohexanoic acid (ε-Ahx) to generate the bifunctional chelating agent diacetyl-2-(N 4 -methyl-3-thiosemicarbazone)-3-[N 4 -(amino)-(6-aminohexanoic acid)-3-thiosemicarbazone], H 2 ATSM/A-ε-Ahx (1), suitable for conjugation to glutamine (Gln) residues of bioactive molecules via TGase. The feasibility of the TGase reaction in the synthesis of a bioconjugate derivative was investigated using Substance P (SP) as model peptide. Compounds 1 and H 2 ATSM/A-ε-Ahx-SP (2) were labelled with nitride-technetium-99m, obtaining the complexes [ 99m Tc][Tc(N)(ATSM/A-ε-Ahx)] ( 99m Tc1) and [ 99m Tc][Tc(N)(ATSM/A-ε-Ahx-SP)] ( 99m Tc2). The chemical identity of 99m Tc1 and 99m Tc2 was confirmed by radio/UV-RP-HPLC combined with ESI-MS analysis on the respective carrier-added products 99g/99m Tc1 and 99g/99m Tc2. The stability of the radiolabelled complexes after incubation in various environments was investigated. All the results were compared with those obtained for the corresponding 64 Cu-analogues, 64 Cu1 and 64 Cu2. The TGase reaction allows the conjugation of 1 with the peptide, but it is not highly efficient due to instability of the chelator in the required conditions. The SP-conjugated complexes are unstable in mouse and human sera. However, indeed the BTS system can be exploited as nitride-technetium-99m chelator for highly efficient technetium labelling, thus making compound 1 worthy of further investigations for new targeted technetium and copper radiopharmaceuticals encompassing Single Photon Emission Computed Tomography and Positron Emission Tomography imaging. Copyright © 2018 Elsevier Inc. All rights reserved.

Assessment of potential aluminum chelators in an octanol/aqueous system and in the aluminum-loaded rabbit.

PubMed

Yokel, R A; Kostenbauder, H B

1987-11-01

Aluminum (Al) solubilization from Al borate and its distribution in an octanol/aqueous system (Do/w) were determined in the absence and presence of 12 potential Al chelators. Citrate, N,N'-bis-(2-hydroxybenzyl)ethylenediamine- N,N'-diacetic acid (HBED), cyclohexane-1,2-diaminotetraacetic acid (CDTA), diethylenetriaminepentaacetic acid (DTPA), nitrilotriacetic acid (NTA), desferrioxamine, and ethylenediamine-N,N'-bis(2-dihydroxyphenylacetic acid) (EDDHA) were 55 to over 100% efficient in solubilizing equimolar amounts of Al. Tetracycline, EDTA, and 2,3-dihydroxybenzoic acid (DHBA) were less than 20% efficient. 1,4-Dioxane and fluoride were ineffective. The Do/w of Al averaged 0.005. The Do/w of the Al.chelator complex was generally less than that of Al, except for HBED and tetracycline (0.04 and 0.96, respectively). The Do/w of DHBA, desferrioxamine, EDDHA, and HBED were not influenced by Al, but tetracycline became more lipophilic. These compounds were tested for their ability to increase urinary Al excretion in Al-loaded rabbits. Chelators were given po weekly beginning 2 weeks after Al loading. Urine was obtained hourly from 3 hr prior to 6 hr after chelator administration and analyzed for Al. Fluoride and tetracycline (450 and 4500 mumol/kg) and citrate, NTA, EDTA, CDTA, DTPA, DHBA, HBED, and 1,4-dioxane (150 and 1500 mumol/kg) were ineffective. Following HBED administration, some of the Al-loaded rabbits died, presumably due to redistribution of Al within the rabbit. Following DTPA administration, some of the Al-loaded rabbits died, presumably due to DTPA. Oral EDDHA (1500 mumol/kg) significantly increased urinary Al excretion. EDDHA and desferrioxamine (150 mumol/kg) were administered by po, sc, and iv routes and were found to have comparable potency. The in vitro results may explain some of the in vivo findings. The in vitro methods may be useful to screen out compounds with no chelation potential. EDDHA-like compounds may have potential as alternatives to desferrioxamine in the prevention or treatment of Al accumulation and Al-induced toxicity.

Development of iron chelators for Cooley's anemia. Final report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Crosby, W.H.; Green, R.

Iron chelators were screened in an iron-loaded rat model using selective radioiron probes. In all experiments, chelators D and F, in that order, induced significant loss of radioiron compared with controls. However, use of chelator D was associated with side effects, and resulted in the death of some animals. There was some evidence that chelator A also caused iron loss significantly greater than controls. Chelators B, C and E were without apparent enhancing effect on radioiron excretion. This was a blind study and the compounds used were A - 2,3-Dihydroxybenzoic acid; B - N,N1-Dimethyladipohydroxamic acid; C - DL-Phenylalanine hydroxamic acid;more » D - Ethylenediamine-N,N1-bis(2-hydroxphenylacetic acid); E - Propionohydroxamic acid; and F - Deferrioxamine B.« less

Clickable, Hydrophilic Ligand for fac-[MI(CO)3]+ (M = Re/99mTc) Applied in an S-Functionalized α-MSH Peptide

PubMed Central

2015-01-01

The copper(I)-catalyzed azide–alkyne cycloaddition (CuAAC) click reaction was used to incorporate alkyne-functionalized dipicolylamine (DPA) ligands (1 and 3) for fac-[MI(CO)3]+ (M = Re/99mTc) complexation into an α-melanocyte stimulating hormone (α-MSH) peptide analogue. A novel DPA ligand with carboxylate substitutions on the pyridyl rings (3) was designed to increase the hydrophilicity and to decrease in vivo hepatobiliary retention of fac-[99mTcI(CO)3]+ complexes used in single photon emission computed tomography (SPECT) imaging studies with targeting biomolecules. The fac-[ReI(CO)3(3)] complex (4) was used for chemical characterization and X-ray crystal analysis prior to radiolabeling studies between 3 and fac-[99mTcI(OH2)3(CO)3]+. The corresponding 99mTc complex (4a) was obtained in high radiochemical yields, was stable in vitro for 24 h during amino acid challenge and serum stability assays, and showed increased hydrophilicity by log P analysis compared to an analogous complex with nonfunctionalized pyridine rings (2a). An α-MSH peptide functionalized with an azide was labeled with fac-[MI(CO)3]+ using both click, then chelate (CuAAC reaction with 1 or 3 followed by metal complexation) and chelate, then click (metal complexation of 1 and 3 followed by CuAAC with the peptide) strategies to assess the effects of CuAAC conditions on fac-[MI(CO)3]+ complexation within a peptide framework. The peptides from the click, then chelate strategy had different HPLC tR’s and in vitro stabilities compared to those from the chelate, then click strategy, suggesting nonspecific coordination of fac-[MI(CO)3]+ using this synthetic route. The fac-[MI(CO)3]+-complexed peptides from the chelate, then click strategy showed >90% stability during in vitro challenge conditions for 6 h, demonstrated high affinity and specificity for the melanocortin 1 receptor (MC1R) in IC50 analyses, and led to moderately high uptake in B16F10 melanoma cells. Log P analysis of the 99mTc-labeled peptides confirmed the enhanced hydrophilicity of the peptide bearing the novel, carboxylate-functionalized DPA chelate (10a′) compared to the peptide with the unmodified DPA chelate (9a′). In vivo biodistribution analysis of 9a′ and 10a′ showed moderate tumor uptake in a B16F10 melanoma xenograft mouse model with enhanced renal uptake and surprising intestinal uptake for 10a′ compared to predominantly hepatic accumulation for 9a′. These results, coupled with the versatility of CuAAC, suggests this novel, hydrophilic chelate can be incorporated into numerous biomolecules containing azides for generating targeted fac-[MI(CO)3]+ complexes in future studies. PMID:24568284

Garlic's ability to prevent in vitro Cu2+-induced lipoprotein oxidation in human serum is preserved in heated garlic: effect unrelated to Cu2+-chelation

PubMed Central

Pedraza-Chaverrí, José; Gil-Ortiz, Mariana; Albarrán, Gabriela; Barbachano-Esparza, Laura; Menjívar, Marta; Medina-Campos, Omar N

2004-01-01

Background It has been shown that several extracts and compounds derived from garlic are able to inhibit Cu2+-induced low density lipoprotein oxidation. In this work we explored if the ability of aqueous garlic extract to prevent in vitro Cu2+-induced lipoprotein oxidation in human serum is affected by heating (a) aqueous garlic extracts or (b) garlic cloves. In the first case, aqueous extract of raw garlic and garlic powder were studied. In the second case, aqueous extract of boiled garlic cloves, microwave-treated garlic cloves, and pickled garlic were studied. It was also studied if the above mentioned preparations were able to chelate Cu2+. Methods Cu2+-induced lipoprotein oxidation in human serum was followed by the formation of conjugated dienes at 234 nm and 37°C by 240 min in a phosphate buffer 20 mM, pH 7.4. Blood serum and CuSO4 were added to a final concentration of 0.67% and 0.0125 mM, respectively. The lag time and the area under the curve from the oxidation curves were obtained. The Cu2+-chelating properties of garlic extracts were assessed using an approach based upon restoring the activity of xanthine oxidase inhibited in the presence of 0.050 mM Cu2+. The activity of xanthine oxidase was assessed by monitoring the production of superoxide anion at 560 nm and the formation of uric acid at 295 nm. Data were compared by parametric or non-parametric analysis of variance followed by a post hoc test. Results Extracts from garlic powder and raw garlic inhibited in a dose-dependent way Cu2+-induced lipoprotein oxidation. The heating of garlic extracts or garlic cloves was unable to alter significantly the increase in lag time and the decrease in the area under the curve observed with the unheated garlic extracts or raw garlic. In addition, it was found that the garlic extracts were unable to chelate Cu2+. Conclusions (a) the heating of aqueous extracts of raw garlic or garlic powder or the heating of garlic cloves by boiling, microwave or pickling do not affect garlic's ability to inhibit Cu2+-induced lipoprotein oxidation in human serum, and (b) this ability is not secondary to Cu2+-chelation. PMID:15341661

Toxicological and pharmacological effects of gadolinium and samarium chlorides

PubMed Central

Haley, T. J.; Raymond, K.; Komesu, N.; Upham, H. C.

1961-01-01

A study has been made of the toxicology and pharmacology of gadolinium and samarium chlorides. The symptoms of acute toxicity following intraperitoneal injection are described. The chronic oral ingestion of both chemicals for 12 weeks produced no effects on growth or the blood picture, and only the male rats receiving gadolinium chloride showed liver damage. The pharmacological responses to both chemicals were mainly depressant on all systems studied, and death was associated with cardiovascular collapse coupled with respiratory paralysis. The greatest damage seen was on abraded skin, where non-healing ulcers were produced by both chemicals, whereas irritation of intact skin and ocular tissues was only transient in nature. PMID:13903826

High spatial resolution free-breathing 3D late gadolinium enhancement cardiac magnetic resonance imaging in ischaemic and non-ischaemic cardiomyopathy: quantitative assessment of scar mass and image quality.

PubMed

Bizino, Maurice B; Tao, Qian; Amersfoort, Jacob; Siebelink, Hans-Marc J; van den Bogaard, Pieter J; van der Geest, Rob J; Lamb, Hildo J

2018-04-06

To compare breath-hold (BH) with navigated free-breathing (FB) 3D late gadolinium enhancement cardiac MRI (LGE-CMR) MATERIALS AND METHODS: Fifty-one patients were retrospectively included (34 ischaemic cardiomyopathy, 14 non-ischaemic cardiomyopathy, three discarded). BH and FB 3D phase sensitive inversion recovery sequences were performed at 3T. FB datasets were reformatted into normal resolution (FB-NR, 1.46x1.46x10mm) and high resolution (FB-HR, isotropic 0.91-mm voxels). Scar mass, scar edge sharpness (SES), SNR and CNR were compared using paired-samples t-test, Pearson correlation and Bland-Altman analysis. Scar mass was similar in BH and FB-NR (mean ± SD: 15.5±18.0 g vs. 15.5±16.9 g, p=0.997), with good correlation (r=0.953), and no bias (mean difference ± SD: 0.00±5.47 g). FB-NR significantly overestimated scar mass compared with FB-HR (15.5±16.9 g vs 14.4±15.6 g; p=0.007). FB-NR and FB-HR correlated well (r=0.988), but Bland-Altman demonstrated systematic bias (1.15±2.84 g). SES was similar in BH and FB-NR (p=0.947), but significantly higher in FB-HR than FB-NR (p<0.01). SNR and CNR were lower in BH than FB-NR (p<0.01), and lower in FB-HR than FB-NR (p<0.01). Navigated free-breathing 3D LGE-CMR allows reliable scar mass quantification comparable to breath-hold. During free-breathing, spatial resolution can be increased resulting in improved sharpness and reduced scar mass. • Navigated free-breathing 3D late gadolinium enhancement is reliable for myocardial scar quantification. • High-resolution 3D late gadolinium enhancement increases scar sharpness • Ischaemic and non-ischaemic cardiomyopathy patients can be imaged using free-breathing LGE CMR.

Synthesis of Copper-Chelates Derived from Amino Acids and Evaluation of Their Efficacy as Copper Source and Growth Stimulator for Lactuca sativa in Nutrient Solution Culture.

PubMed

Kaewchangwat, Narongpol; Dueansawang, Sattawat; Tumcharern, Gamolwan; Suttisintong, Khomson

2017-11-15

Five tetradentate ligands were synthesized from l-amino acids and utilized for the synthesis of Cu(II)-chelates 1-5. The efficacy of Cu(II)-chelates as copper (Cu) source and growth stimulator in hydroponic cultivation was evaluated with Lactuca sativa. Their stability test was performed at pH 4-10. The results suggested that Cu(II)-chelate 3 is the most pH tolerant complex. Levels of Cu, Zn, and Fe accumulated in plants supplied with Cu(II)-chelates were compared with those supplied with CuSO 4 at the same Cu concentration of 8.0 μM. The results showed that Cu(II)-chelate 3 significantly enhanced Cu, Zn, and Fe content in shoot by 35, 15, and 48%, respectively. Application of Cu(II)-chelate 3 also improved plant dry matter yield by 54%. According to the results, Cu(II)-chelate 3 demonstrated the highest stimulating effect on plant growth and plant mineral accumulation so that it can be used as an alternative to CuSO 4 for supplying Cu in nutrient solutions and enhancing the plant growth.

Investigation of on-line chelant addition to PWR steam generators. Annual report, 1981

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tvedt, T.J.; Wallace, S.L.; Griffin, F. Jr.

1982-11-01

The thermostability of both ethylenediaminetetraacetic acid (EDTA) and hydroxyethylethylenediamininetriacetic acid (HEDTA) metal chelates in all volatile treatment water chemistry (AVT) was shown to be greater than or equal to thermostability of EDTA metal chelates in phosphate-sulfite water chemistry. HEDTA metal chelates were shown to have a much greater stability than EDTA metal chelates. Using samples taken from the EDTA metal chelate thermostability studies and samples from Commonwealth Research Corporation (CRC) model steam generators (MSG), EDTA decomposition products were determined. Active metal surfaces were shown to become passivated when exposed to EDTA and HEDTA concentrations as high as 0.1% w/w inmore » AVT. Trace amounts of iron in the water were found to increase the rate of passivation. Material balance and visual inspection data from CRC model steam generators showed that metal is being transported through and cleaning from the MSG's. EDTA metal chelates were removed from chelate solutions by passing the solutions over strong anion exchange resins.« less

Synthesis of Iminodiacetate Functionalized Polypropylene Films and Their Efficacy as Antioxidant Active-Packaging Materials.

PubMed

Lin, Zhuangsheng; Roman, Maxine J; Decker, Eric A; Goddard, Julie M

2016-06-08

The introduction of metal-chelating ligands to the food-contact surface of packaging materials may enable the removal of synthetic chelators (e.g., ethylenediamine tetra-acetic acid (EDTA)) from food products. In this study, the metal-chelating ligand iminodiacetate (IDA) was covalently grafted onto polypropylene surfaces to produce metal-chelating active-packaging films. The resulting films were able to chelate 138.1 ± 26 and 210.0 ± 28 nmol/cm(2) Fe(3+) and Cu(2+) ions, respectively, under acidic conditions (pH 3.0). The films demonstrated potent antioxidant efficacy in two model food systems. In an emulsified-oil system, the chelating materials extended the lag phase of both lipid hydroperoxide and hexanal formation from 5 to 25 days and were as effective as EDTA. The degradation half-life of ascorbic acid in an aqueous solution was extended from 5 to 14 days. This work demonstrates the potential application of surface-grafted chelating IDA ligands as effective antioxidant active food-packaging materials.

Cu-free 1,3-dipolar cycloaddition click reactions to form isoxazole linkers in chelating ligands for fac-[M(I)(CO)3]+ centers (M = Re, 99mTc).

PubMed

Bottorff, Shalina C; Kasten, Benjamin B; Stojakovic, Jelena; Moore, Adam L; MacGillivray, Leonard R; Benny, Paul D

2014-02-17

Isoxazole ring formation was examined as a potential Cu-free alternative click reaction to Cu(I)-catalyzed alkyne/azide cycloaddition. The isoxazole reaction was explored at macroscopic and radiotracer concentrations with the fac-[M(I)(CO)3](+) (M = Re, (99m)Tc) core for use as a noncoordinating linker strategy between covalently linked molecules. Two click assembly methods (click, then chelate and chelate, then click) were examined to determine the feasibility of isoxazole ring formation with either alkyne-functionalized tridentate chelates or their respective fac-[M(I)(CO)3](+) complexes with a model nitrile oxide generator. Macroscale experiments, alkyne-functionalized chelates, or Re complexes indicate facile formation of the isoxazole ring. (99m)Tc experiments demonstrate efficient radiolabeling with click, then chelate; however, the chelate, then click approach led to faster product formation, but lower yields compared to the Re analogues.

Catalytic superoxide scavenging by metal complexes of the calcium chelator EGTA and contrast agent EHPG.

PubMed

Fisher, Anna E O; Hague, Theresa A; Clarke, Charlotte L; Naughton, Declan P

2004-10-08

Metal ion chelators widely used in experimental protocols and clinical diagnosis are generally assumed to be inert. We previously reported that the ubiquitous chelator EDTA has high levels of superoxide suppressing activity. Here, we report that the common chelators calcium chelator EGTA and contrast agent EHPG have significant activities in suppressing superoxide levels depending on the nature of metal ion chelated. The most active species is Mn(II)-EGTA which exhibited an IC50 value of 0.19 microM for superoxide destruction. In addition, IC50 values for Mn(II)-EHPG and 2Cu(II)-EGTA were 0.69 and 0.60 microM, respectively. In conclusion, Mn(II) and Cu(II) complexes of the common chelators EGTA and EHPG exhibit considerable superoxide scavenging activities. Caution should be employed in their use in biological systems where superoxide has a key role and they may be useful for the development of catalytic anti-oxidants. Copyright 2004 Elsevier Inc.

Iron Chelation

MedlinePlus

... fortified cereals and eggs. What is Iron Chelation Therapy? Drugs called iron chelators remove extra iron from ... form that must be dissolved in juice or water and taken (by mouth) once a day. Most ...

Preparation of 152Gd targets from a small quantity of gadolinium oxide in a pyrochemical reaction

NASA Astrophysics Data System (ADS)

Lipski, A. R.

1995-02-01

A simple method utilizing small amounts (< 5 mg) of isotopically enriched material for the production of gadolinium targets is discussed. An electrostatically focused e-gun is used in the procedure in which 152Gd 2O 3 powder undergoes reduction-distillation and deposition onto an Fe foil.

Characteristics of Gadolinium Oxide Nanoparticles Using Terahertz Spectroscopy (abstract)

NASA Astrophysics Data System (ADS)

Lee, Dongkyu; Maeng, Inhee; Oh, Seung Jae; Kim, Taekhoon; Cho, Byung Kyu; Lee, Kwangyeol; Son, Joo-Hiuk

2009-04-01

The penetration property of the terahertz electromagnetic (THz) wave is relevant to its use. We used the THz wave spectroscopy system which easily penetrates some materials that do not contain water, e.g., plastic and ceramics. The system has been developed for several purposes, including measuring the properties of semiconductors and bio-materials, and detecting plastic bombs and ceramic knives at airports. It is also used for medical imaging systems, such as magnetic resonance imaging (MRI), at some research institutes. It can show not only the difference in amplitude, but also the difference of the phase of each point of sample. MRI technology usually uses contrast agents to enhance the quality of the image. Gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA), made with a heavy metal ion, is commonly used as a clinical MRI contrast agent. Gadolinium oxide (Gd2O3) nanoparticle is a new contrast agent. It serves to equip the core of each particle with antibodies or ligands. It can freely circulate in blood vessels without amassing in the liver or lungs. This study shows the characteristics of gadolinium oxide nanoparticles to further advance terahertz medical imaging.

Measurement of gadolinium retention: current status and review from an applied radiation physics perspective.

PubMed

Gräfe, James L; McNeill, Fiona E

2018-06-28

This article briefly reviews the main measurement techniques for the non-invasive detection of residual gadolinium (Gd) in those exposed to gadolinium-based contrast agents (GBCAs). Approach and Main results: The current status of in vivo Gd measurement is discussed and is put into the context of concerns within the radiology community. The main techniques are based on applied atomic/nuclear medicine utilizing the characteristic atomic and nuclear spectroscopic signature of Gd. The main emission energies are in the 40-200 keV region and require spectroscopic detectors with good energy resolution. The two main techniques, prompt gamma neutron activation analysis and x-ray fluorescence, provide adequate detection limits for in vivo measurement, whilst delivering a low effective radiation dose on the order of a few µSv. Gadolinium is being detected in measureable quantities in people with healthy renal function who have received FDA approved GBCAs. The applied atomic/nuclear medicine techniques discussed in this review will be useful in determining the significance of this retention, and will help on advising future administration protocols.

K3 Li3 Gd7 (BO3 )9 : A New Gadolinium-Rich Orthoborate for Cryogenic Magnetic Cooling.

PubMed

Xia, Mingjun; Shen, Shipeng; Lu, Jun; Sun, Young; Li, Rukang

2018-03-02

Magnetic cooling technology based on magnetocaloric effect (MCE) has attracted great interest in obtaining extremely low temperatures, for example, for space exploration. Here, we grew a new gadolinium-rich orthoborate K 3 Li 3 Gd 7 (BO 3 ) 9 (1) as a promising cryogenic magnetic coolant. It exhibits a complicated three dimensional framework constructed from BO 3 groups and gadolinium-oxygen chains. The Gd-O chain consists of two types of clusters of Gd 3 O 20 and Gd 3 O 19 interconnection by Gd(4)O 8 polyhydron. Due to its high gadolinium concentration, a large -ΔS m of 56.6 J kg -1  K -1 for 1 was obtained at 2 K and ΔH=7 T, much larger than that of the commercial benchmark Gd 3 Ga 5 O 12 (GGG) crystal (38.4 J kg -1  K -1 ), suggesting it to be an excellent MCE material. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Grape seed proanthocyanidin extract attenuates oxidant injury in cardiomyocytes.

PubMed

Shao, Zuo-Hui; Becker, Lance B; Vanden Hoek, Terry L; Schumacker, Paul T; Li, Chang-Qing; Zhao, Danhong; Wojcik, Kim; Anderson, Travis; Qin, Yimin; Dey, Lucy; Yuan, Chun-Su

2003-06-01

This study sought to test whether grape seed proanthocyanidin extract (GSPE) attenuates exogenous and endogenous oxidant stress induced in chick cardiomyocytes and whether this cytoprotection is mediated by PKC activation, mito K(ATP) channel opening, NO production, oxidant scavenging, or iron chelating effects. Cells were exposed to hydrogen peroxide (H(2)O(2)) (exogenous oxidant stress, 0.5mM) or antimycin A (endogenous oxidant stress, 100 micro M) for 2h following pretreatment with GSPE at various concentrations for 2h. Cells were also pretreated with GSPE or with inhibitors of PKC (chelerytherine), mito K(ATP) channel (5-hydroxydecanoate), nitric oxide synthase (nitro-L-arginine methyl ester) for 2h. Oxidant stress was measured by 2',7'-dichlorofluorescin diacetate and cell viability was assessed using propidium iodide. Free radical scavenging and iron chelating ability was tested in vitro. GSPE dose-dependently attenuated oxidant formation and significantly improved cell survival and contractile function. However, inhibitors of PKC, mito K(ATP) channel or NO synthase failed to abolish the protective action of GSPE during H(2)O(2) or antimycin A exposure. In vitro studies suggested that GSPE scavenges H(2)O(2), hydroxyl radical and superoxide, and may chelate iron. These results indicate that GSPE confers cardioprotection against exogenous H(2)O(2)- or antimycin A-induced oxidant injury. Its effect does not require PKC, mito K(ATP) channel, or NO synthase, presumably because it acts by reactive oxygen species scavenging and iron chelating directly.

The influence of EDDS and EDTA on the uptake of heavy metals of Cd and Cu from soil with tobacco Nicotiana tabacum.

PubMed

Evangelou, Michael W H; Bauer, Uwe; Ebel, Mathias; Schaeffer, Andreas

2007-06-01

Phytoextraction, the use of plants to extract contaminants from soils and groundwater, is a promising approach for cleaning up soils contaminated with heavy metals. In order to enhance phytoextraction the use of chelating agents has been proposed. This study aims to assess whether ethylene diamine disuccinate (EDDS), a biodegradable chelator, can be used for enhanced phytoextraction purposed, as an alternative to ethylene diamine tetraacetate (EDTA). EDDS revealed a higher toxicity to tobacco (Nicotiana tabacum) in comparison to EDTA, but no toxicity to microorganisms. The uptake of Cu was increased by the addition of EDTA and EDDS, while no increase was observed in the uptake of Cd. Both chelating agents showed a very low root to shoot translocation capability and the translocation factor was lower than the one of the control. Heavy metals where significantly more phytoavailable than in the control, even after harvesting, resulting in a high heavy metal leaching possibility, probably owing to a low biodegradation rate of EDDS. New seedlings which were transplanted into the EDDS treated pots 7d after the phytoextraction experiment, showed signs of necrosis and chlorosis, which resulted in a significantly lower biomass in comparison to the control. The seedlings on the EDTA treated pots showed no toxicity signs. Contrary to previous opinions the results of this study revealed the chelating agents EDTA and EDDS as unsuitable for enhanced phytoextraction using tobacco.

Effects of chelating agents on the mineral content of root canal dentin.

PubMed

Cobankara, Funda Kont; Erdogan, Hilal; Hamurcu, Mehmet

2011-12-01

The objective of this in vitro study was to assess the effect of several chelating agents on the mineral content of root dentin. Extracted human mandibular incisor roots were prepared and divided into groups according to the following irrigation protocols: 1) 17% ethylenediaminetetraacetic acid (EDTA); 2) 10% citric acid solution; 3) 18% etidronate; 4) 2.25% peracetic acid; 5) and deionized water (control). Dentin chips were obtained (Gates-Glidden nos. 3, 4, and 5). The levels of different minerals were analyzed with the use of inductively coupled plasma-atomic emission spectrometry (ICP-AES). 1) Peracetic acid significantly decreased P, K, Mg, Na, and S levels compared with the other groups (P < .05). 2) S decreased by different levels in all of the chelating solutions (P < .05), and the greatest decrease was observed in peracetic acid. 3) Ca levels significantly decreased in peracetic acid, citric acid, and EDTA (P < .05). 4) Mn levels significantly decreased in the citric acid and peracetic acid groups (P < .05). 5) Na and Zn levels significantly decreased in the peracetic acid, citric acid, and etidronate groups (P < .05). The chelation agents can create different effects on mineral contents of root dentin, so it is important to know what effects each solution will have on root dentin before their clinical use. In addition, according to the results of this in vitro study, it might be recommended that peracetic acid, in particular, should be used with caution. Copyright © 2011 Mosby, Inc. All rights reserved.

Physicochemical impact studies of gamma rays on "aspirin" analgesics drug and its metal complexes in solid form: Synthesis, spectroscopic and biological assessment of Ca(II), Mg(II), Sr(II) and Ba(II) aspirinate complexes

NASA Astrophysics Data System (ADS)

Refat, Moamen S.; Sharshar, T.; Elsabawy, Khaled M.; Heiba, Zein K.

2013-09-01

Metal aspirinate complexes, M2(Asp)4, where M is Mg(II), Ca(II), Sr(II) or Ba(II) are formed by refluxed of aspirin (Asp) with divalent non-transition metal ions of group (II) and characterized by elemental analysis and spectroscopic measurements (infrared, electronic, 1H NMR, Raman, X-ray powder diffraction and scanning electron microscopy). Elemental analysis of the chelates suggests the stoichiometry is 1:2 (metal:ligand). Infrared spectra of the complexes agree with the coordination to the central metal atom through three donation sites of two oxygen atoms of bridge bidentate carboxylate group and oxygen atom of sbnd Cdbnd O of acetyl group. Infrared spectra coupled with the results of elemental analyzes suggested a distorted octahedral structure for the M(II) aspirinate complexes. Gamma irradiation was tested as a method for stabilization of aspirin as well as their complexes. The effect of gamma irradiation, with dose of 80 Gy, on the properties of aspirinate complexes was studied. The aspirinate chelates have been screened for their in vitro antibacterial activity against four bacteria, gram-positive (Bacillus subtilis and Staphylococcus aureus) and gram-negative (Escherichia coli and Pseudomonas aeruginosa) and two strains of fungus (Aspergillus flavus and Candida albicans). The metal chelates were shown to possess more antibacterial activity than the free aspirin chelate.

Alternative/Complementary Approaches to Treatment of Children with Autism Spectrum Disorders.

ERIC Educational Resources Information Center

Levy, Susan E.; Hyman, Susan L.

2002-01-01

This article reviews common complementary or alternative medicine (CAM) treatments used to address symptoms of autistic spectrum disorders, including vitamin supplements, medications, antibiotics, antifungals, diet strategies, chelation/mercury detoxification, and nonbiologic treatments. Strategies that professionals may use in assessing the…

Imaging of cauda equina edema in lumbar canal stenosis by using gadolinium-enhanced MR imaging: experimental constriction injury.

PubMed

Kobayashi, S; Uchida, K; Takeno, K; Baba, H; Suzuki, Y; Hayakawa, K; Yoshizawa, H

2006-02-01

It has been reported that disturbance of blood flow arising from circumferential compression of the cauda equina by surrounding tissue plays a major role in the appearance of neurogenic intermittent claudication (NIC) associated with lumbar spinal canal stenosis (LSCS). We created a model of LSCS to clarify the mechanism of enhancement within the cauda equina on gadolinium-enhanced MR images from patients with LSCS. In 20 dogs, a lumbar laminectomy was performed by applying circumferential constriction to the cauda equina by using a silicon tube, to produce 30% stenosis of the circumferential diameter of the dural tube. After 1 and 3 weeks, gadolinium and Evans blue albumin were injected intravenously at the same time. The sections were used to investigate the status of the blood-nerve barrier function under a fluorescence microscope and we compared gadolinium-enhanced MR images with Evans blue albumin distribution in the nerve. The other sections were used for light and transmission electron microscopic study. In this model, histologic examination showed congestion and dilation in many of the intraradicular veins, as well as inflammatory cell infiltration. The intraradicular edema caused by venous congestion and Wallerian degeneration can also occur at sites that are not subject to mechanical compression. Enhanced MR imaging showed enhancement of the cauda equina at the stenosed region, demonstrating the presence of edema. Gadolinium-enhanced MR imaging may be a useful tool for the diagnosis of microcirculatory disorders of the cauda equina associated with LSCS.

Assessment of liver function in primary biliary cirrhosis using Gd-EOB-DTPA-enhanced liver MRI.

PubMed

Nilsson, Henrik; Blomqvist, Lennart; Douglas, Lena; Nordell, Anders; Jonas, Eduard

2010-10-01

Gd-EOB-DTPA (gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid) is a gadolinium-based hepatocyte-specific contrast agent for magnetic resonance imaging (MRI). The aim of this study was to determine whether the hepatic uptake and excretion of Gd-EOB-DTPA differ between patients with primary biliary cirrhosis (PBC) and healthy controls, and whether differences could be quantified. Gd-EOB-DTPA-enhanced liver MRI was performed in 20 healthy volunteers and 12 patients with PBC. The uptake of Gd-EOB-DTPA was assessed using traditional semi-quantitative parameters (C(max) , T(max) and T(1/2) ), as well as model-free parameters derived after deconvolutional analysis (hepatic extraction fraction [HEF], input-relative blood flow [irBF] and mean transit time [MTT]). In each individual, all parameters were calculated for each liver segment and the median of the segmental values was used to define a global liver median (GLM). Although the PBC patients had relatively mild disease according to their Model for End-stage Liver Disease (MELD), Child-Pugh and Mayo risk scores, they had significantly lower HEF and shorter MTT values compared with the healthy controls. These differences significantly increased with increasing MELD and Child-Pugh scores. Dynamic hepatocyte-specific contrast-enhanced MRI (DHCE-MRI) has a potential role as an imaging-based liver function test. The high spatial resolution of MRI enables hepatic function to be assessed on segmental and sub-segmental levels. © 2010 International Hepato-Pancreato-Biliary Association.

Interference of medical contrast media on laboratory testing.

PubMed

Lippi, Giuseppe; Daves, Massimo; Mattiuzzi, Camilla

2014-01-01

The use of contrast media such as organic iodine molecules and gadolinium contrast agents is commonplace in diagnostic imaging. Although there is widespread perception that side effects and drug interactions may be the leading problems caused by these compounds, various degrees of interference with some laboratory tests have been clearly demonstrated. Overall, the described interference for iodinate contrast media include inappropriate gel barrier formation in blood tubes, the appearance of abnormal peaks in capillary zone electrophoresis of serum proteins, and a positive bias in assessment of cardiac troponin I with one immunoassay. The interference for gadolinium contrast agents include negative bias in calcium assessment with ortho-cresolphthalein colorimetric assays and occasional positive bias using some Arsenazo reagents, negative bias in measurement of angiotensin converting enzyme (ACE) and zinc (colorimetric assay), as well as positive bias in creatinine (Jaffe reaction), total iron binding capacity (TIBC, ferrozine method), magnesium (calmagite reagent) and selenium (mass spectrometry) measurement. Interference has also been reported in assessment of serum indices, pulse oximetry and methaemoglobin in samples of patients receiving Patent Blue V. Under several circumstances the interference was absent from manufacturer-supplied information and limited to certain type of reagents and/or analytes, so that local verification may be advisable to establish whether or not the test in use may be biased. Since the elimination half-life of these compounds is typically lower than 2 h, blood collection after this period may be a safer alternative in patients who have received contrast media for diagnostic purposes.

Interference of medical contrast media on laboratory testing

PubMed Central

Lippi, Giuseppe; Daves, Massimo; Mattiuzzi, Camilla

2014-01-01

The use of contrast media such as organic iodine molecules and gadolinium contrast agents is commonplace in diagnostic imaging. Although there is widespread perception that side effects and drug interactions may be the leading problems caused by these compounds, various degrees of interference with some laboratory tests have been clearly demonstrated. Overall, the described interference for iodinate contrast media include inappropriate gel barrier formation in blood tubes, the appearance of abnormal peaks in capillary zone electrophoresis of serum proteins, and a positive bias in assessment of cardiac troponin I with one immunoassay. The interference for gadolinium contrast agents include negative bias in calcium assessment with ortho-cresolphthalein colorimetric assays and occasional positive bias using some Arsenazo reagents, negative bias in measurement of angiotensin converting enzyme (ACE) and zinc (colorimetric assay), as well as positive bias in creatinine (Jaffe reaction), total iron binding capacity (TIBC, ferrozine method), magnesium (calmagite reagent) and selenium (mass spectrometry) measurement. Interference has also been reported in assessment of serum indices, pulse oximetry and methaemoglobin in samples of patients receiving Patent Blue V. Under several circumstances the interference was absent from manufacturer-supplied information and limited to certain type of reagents and/or analytes, so that local verification may be advisable to establish whether or not the test in use may be biased. Since the elimination half-life of these compounds is typically lower than 2 h, blood collection after this period may be a safer alternative in patients who have received contrast media for diagnostic purposes. PMID:24627717

Phosphonate Pendant Armed Propylene Cross-Bridged Cyclam: Synthesis and Evaluation as a Chelator for Cu-64

PubMed Central

2015-01-01

A propylene cross-bridged macrocyclic chelator with two phosphonate pendant arms (PCB-TE2P) was synthesized from cyclam. Various properties of the synthesized chelator, including Cu-complexation, Cu-complex stability, 64Cu-radiolabeling, and in vivo behavior, were studied and compared with those of a previously reported propylene cross-bridged chelator (PCB-TE2A). PMID:26617972

Acute side effects of three commonly used gadolinium contrast agents in the paediatric population.

PubMed

Neeley, Chris; Moritz, Michael; Brown, Jeffrey J; Zhou, Yihua

2016-07-01

To determine the incidence of acute side effects of three commonly used gadolinium contrast agents in the paediatric population. A retrospective review of medical records was performed to determine the incidence of acute adverse side effects of i.v. gadolinium contrast agents [MultiHance(®) (Bracco Diagnostics Inc., Princeton, NJ), Magnevist(®) (Bayer Healthcare Pharmaceuticals, Wayne, NJ) or Gadavist(®) (Bayer HealthCare Pharmaceuticals)] in paediatric patients. 40 of the 2393 patients who received gadolinium contrast agents experienced acute side effects, representing an incidence of 1.7%. The majority of the acute side effects (in 30 patients) were nausea and vomiting. The incidence was significantly higher in non-sedated patients (2.37% vs 0.7%; p = 0.0018). Furthermore, without sedation, the incidence of both nausea and vomiting was significantly higher in children receiving MultiHance, with a 4.48% incidence of nausea when compared with Magnevist (0.33%, p < 0.0001) and Gadavist (0.28%, p < 0.0001) and a 2.36% incidence of vomiting compared with those for Magnevist (0.50%, p = 0.0054) and Gadavist (0.28%, p = 0.014), whereas no difference was observed between Magnevist and Gadavist within the power of the study. In addition, there was no apparent difference between any of the three contrast agents for the incidence of allergy or other acute side effects detected, given the sample size. The gadolinium contrast agents MultiHance, Magnevist and Gadavist have a low incidence of acute side effects in the paediatric population, a rate that is further reduced in moderately sedated patients. MultiHance demonstrated significantly increased incidence of gastrointestinal symptoms compared with Magnevist and Gadavist. The incidence of acute side effects of three commonly used gadolinium contrast agents was determined in the paediatric population, which can have clinical implications.

Monte Carlo simulation of energy absorbed in phenolic ESR dosimeters added with gadolinium exposed to thermal, epithermal and fast neutrons

NASA Astrophysics Data System (ADS)

Longo, A.; Collura, G.; Gallo, S.; Bartolotta, A.; Marrale, M.

2017-11-01

In this work analyses of the energy released per unit mass in phenolic compound exposed to neutron beams were performed with the aim of predicting the increase in dose achievable by addition of gadolinium (Gd) inside the pellets. In particular, Monte Carlo (MC) simulations were carried out for IRGANOX® 1076 phenolic compound irradiated with neutron beams with different energy spectra at various depths inside a water phantom. The addition of gadolinium increases sensitivity of phenolic ESR (electron spin resonance) dosimeters to neutrons thanks to the high gadolinium cross section for neutron capture and to the large number of secondary particles (mainly Auger and internal conversion electrons) which are able to release energy inside the sensitive material layers. For small depths in water phantom and low energy neutron spectra the increase in dose due to gadolinium is large (more than a factor 50). The enhancement is smaller in case of epithermal neutron beam, whereas the increase in dose for fast neutrons is less than 50%. In order to have a comparison with other ESR dosimeters the energy released per unit mass in phenolic compound was compared with that calculated in alanine pellets. For thermal neutron beams the energy released in phenolic compound with gadolinium is comparable to that released in alanine for small depths in phantom, whereas it is larger than in alanine for large depths. In case of epithermal and fast neutron beams the energy released in phenolic compound is larger than in alanine samples because the elastic scattering with hydrogen nuclei is more probable for high neutron energies and this phenolic compound is characterized by an higher number of 1H nuclei than alanine. All results here found suggest that these phenolic pellets could be fruitfully used for dosimetric applications in Neutron Capture Therapy.

Chelation for Coronary Heart Disease

MedlinePlus

... also turn to chelation therapy using disodium EDTA (ethylene diamine tetra-acetic acid), a controversial complementary health ... and answers about two trials of an EDTA (ethylene diamine tetra-acetic acid) chelation therapy regimen for ...

Effective sulfur and energy recovery from hydrogen sulfide through incorporating an air-cathode fuel cell into chelated-iron process.

PubMed

Sun, Min; Song, Wei; Zhai, Lin-Feng; Cui, Yu-Zhi

2013-12-15

The chelated-iron process is among the most promising techniques for the hydrogen sulfide (H2S) removal due to its double advantage of waste minimization and resource recovery. However, this technology has encountered the problem of chelate degradation which made it difficult to ensure reliable and economical operation. This work aims to develop a novel fuel-cell-assisted chelated-iron process which employs an air-cathode fuel cell for the catalyst regeneration. By using such a process, sulfur and electricity were effectively recovered from H2S and the problem of chelate degradation was well controlled. Experiment on a synthetic sulfide solution showed the fuel-cell-assisted chelated-iron process could maintain high sulfur recovery efficiencies generally above 90.0%. The EDTA was preferable to NTA as the chelating agent for electricity generation, given the Coulombic efficiencies (CEs) of 17.8 ± 0.5% to 75.1 ± 0.5% for the EDTA-chelated process versus 9.6 ± 0.8% to 51.1 ± 2.7% for the NTA-chelated process in the pH range of 4.0-10.0. The Fe (III)/S(2-) ratio exhibited notable influence on the electricity generation, with the CEs improved by more than 25% as the Fe (III)/S(2-) molar ratio increased from 2.5:1 to 3.5:1. Application of this novel process in treating a H2S-containing biogas stream achieved 99% of H2S removal efficiency, 78% of sulfur recovery efficiency, and 78.6% of energy recovery efficiency, suggesting the fuel-cell-assisted chelated-iron process was effective to remove the H2S from gas streams with favorable sulfur and energy recovery efficiencies. Copyright © 2013 Elsevier B.V. All rights reserved.

CaNa2EDTA chelation attenuates cell damage in workers exposed to lead--a pilot study.

PubMed

Čabarkapa, A; Borozan, S; Živković, L; Stojanović, S; Milanović-Čabarkapa, M; Bajić, V; Spremo-Potparević, B

2015-12-05

Lead induced oxidative cellular damage and long-term persistence of associated adverse effects increases risk of late-onset diseases. CaNa2EDTA chelation is known to remove contaminating metals and to reduce free radical production. The objective was to investigate the impact of chelation therapy on modulation of lead induced cellular damage, restoration of altered enzyme activities and lipid homeostasis in peripheral blood of workers exposed to lead, by comparing the selected biomarkers obtained prior and after five-day CaNa2EDTA chelation intervention. The group of smelting factory workers diagnosed with lead intoxication and current lead exposure 5.8 ± 1.2 years were administered five-day CaNa2EDTA chelation. Elevated baseline activity of antioxidant enzymes Cu, Zn-SOD and CAT as well as depleted thiols and increased protein degradation products-carbonyl groups and nitrites, pointing to Pb induced oxidative damage, were restored toward normal values following the treatment. Lead showed inhibitor potency on both RBC AChE and BChE in exposed workers, and chelation re-established the activity of BChE, while RBC AChE remained unaffected. Also, genotoxic effect of lead detected in peripheral blood lymphocytes was significantly decreased after therapy, exhibiting 18.9% DNA damage reduction. Administration of chelation reversed the depressed activity of serum PON 1 and significantly decreased lipid peroxidation detected by the post-chelation reduction of MDA levels. Lactate dehydrogenase LDH1-5 isoenzymes levels showed evident but no significant trend of restoring toward normal control values following chelation. CaNa2EDTA chelation ameliorates the alterations linked with Pb mediated oxidative stress, indicating possible benefits in reducing health risks associated with increased oxidative damage in lead exposed populations. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Study of Anti-Fatigue Effect in Rats of Ferrous Chelates Including Hairtail Protein Hydrolysates

PubMed Central

Huang, Saibo; Lin, Huimin; Deng, Shang-gui

2015-01-01

The ability of ferrous chelates including hairtail protein hydrolysates to prevent and reduce fatigue was studied in rats. After hydrolysis of hairtail surimi with papain, the hairtail protein hydrolysates (HPH) were separated into three groups by range of relative molecular weight using ultrafiltration membrane separation. Hairtail proteins were then chelated with ferrous ions, and the antioxidant activity, the amino acid composition and chelation rate of the three kinds of ferrous chelates including hairtail protein hydrolysates (Fe-HPH) were determined. Among the three groups, the Fe-HPH chelate showing the best conditions was selected for the anti-fatigue animal experiment. For it, experimental rats were randomly divided into seven groups. Group A was designated as the negative control group given distilled water. Group B, the positive control group, was given glutathione. Groups C, D and E were designated as the Fe-HPH chelate treatment groups and given low, medium, and high doses, respectively. Group F was designated as HPH hydrolysate treatment group, and Group G was designated as FeCl2 treatment group. The different diets were orally administered to rats for 20 days. After that time, rats were subjected to forced swimming training after 1 h of gavage. Rats given Fe-FPH chelate had higher haemoglobin regeneration efficiency (HRE), longer exhaustive swimming time and higher SOD activity. Additionally, Fe-FPH chelate was found to significantly decrease the malondialdehyde content, visibly enhance the GSH-Px activity in liver and reduce blood lactic acid of rats. Fe-HPH chelate revealed an anti-fatigue effect, similar to or better than the positive control substance and superior to HPH or Fe when provided alone. PMID:26633476

Kinetic behavior of Fe(o,o-EDDHA)-humic substance mixtures in several soil components and in calcareous soils.

PubMed

Cerdán, Mar; Alcañiz, Sara; Juárez, Margarita; Jordá, Juana D; Bermúdez, Dolores

2007-10-31

Ferric ethylenediamine- N, N'-bis-(o-hydroxyphenylacetic)acid chelate (Fe(o, o-EDDHA)) is one of the most effective Fe fertilizers in calcareous soils. However, humic substances are occasionally combined with iron chelates in drip irrigation systems in order to lower costs. The reactivity of iron chelate-humic substance mixtures in several soil components and in calcareous soils was investigated through interaction tests, and their behavior was compared to the application of iron chelates and humic substances separately. Two commercial humic substances and two Fe(o, o-EDDHA) chelates (one synthesized in the laboratory and one commercial) were used to prepare iron chelate-humic substance mixtures at 50% (w/w). Various soil components (calcium carbonate, gibbsite, amorphous iron oxide, hematite, tenorite, zincite, amorphous Mn oxide, and peat) and three calcareous soils were shaken for 15 days with the mixtures and with iron chelate and humic substance solutions. The kinetic behavior of Fe(o, o-EDDHA) and Fe non-(o,o-EDDHA) (Fe bonded to (o,p-EDDHA) and other polycondensated ligands) and of the different nutrients solubilized after the interaction assay was determined. The results showed that the mixtures did not significantly reduce the retention of Fe(o, o-EDDHA) and Fe non-(o,o-EDDHA) in the soil components and the calcareous soils compared to the iron chelate solutions, but they did produce changes in the retention rate. Moreover, the competition between humic substances and synthetic chelating agents for complexing metal cations limited the effectiveness of the mixtures to mobilize nutrients from the substrates. The presence of Fe(o, p-EDDHA) and other byproducts in the commercial iron chelate had an important effect on the evolution of Fe(o, o-EDDHA) and the nutrient solubilization process.

The heart in transfusion dependent homozygous thalassaemia today – prediction, prevention and management

PubMed Central

Aessopos, Athanassios; Berdoukas, Vasilios; Tsironi, Maria

2008-01-01

Cardiac disease remains the major cause of death in thalassaemia major. This review deals with the mechanisms involved in heart failure development, the peculiar clinical presentation of congestive heart failure and provides guidelines for diagnosis and management of the acute phase of cardiac failure. It emphasizes the need for intensive medical – cardiac care and aggressive iron chelating management as, with such approaches, today, the patients outcomes can be favourable in the long term. It covers advances in the assessment of cardiac iron overload with the use of magnetic resonance imaging and makes recommendations for preventing the onset of cardiac problems by tailoring iron chelation therapy appropriate to the degree of cardiac iron loading found. PMID:18081719

Questions and Answers on Unapproved Chelation Products

MedlinePlus

... OTC) to prevent or treat diseases. Companies are marketing unapproved OTC chelation therapy products to patients with ... 4. Why did FDA take this action? Companies marketing unapproved OTC chelation products with unsubstantiated treatment claims ...

Correction of anemia in a transfusion-dependent patient with primary myelofibrosis receiving iron chelation therapy with deferasirox (Exjade®, ICL670)

PubMed Central

Di Tucci, Anna Angela; Murru, Roberta; Alberti, Daniele; Rabault, Bertrand; Deplano, Simona; Angelucci, Emanuele

2007-01-01

Transfusional iron overload in patients with chronic anemias can result in multiple organ failure. Experience in the management of iron overload in patients with myelodysplastic syndromes is limited, as many do not receive chelation therapy due to short-life expectancy and the difficulties associated with the administration of the current reference standard chelator, deferoxamine. There have, however, been some reports of reduced transfusion requirement associated with chelation therapy in patients with myelodysplastic syndromes and myelofibrosis. Here, we discuss a patient with primary myelofibrosis and related transfusion-dependent anemia who received chelation therapy with the once-daily oral iron chelator, deferasirox. In addition to the reduced iron levels, the patient demonstrated an unexpected reduction in blood transfusion requirement, ultimately resulting in long-lasting transfusion-free survival. PMID:17391307

Development of Iron-Chelating Poly(ethylene terephthalate) Packaging for Inhibiting Lipid Oxidation in Oil-in-Water Emulsions.

PubMed

Johnson, David R; Tian, Fang; Roman, Maxine J; Decker, Eric A; Goddard, Julie M

2015-05-27

Foods such as bulk oils, salad dressings, and nutritionally fortified beverages that are susceptible to oxidative degradation are often packaged in poly(ethylene terephthalate) (PET) bottles with metal chelators added to the food to maintain product quality. In the present work, a metal-chelating active packaging material is designed and characterized, in which poly(hydroxamic acid) (PHA) metal-chelating moieties were grafted from the surface of PET. Biomimetic PHA groups were grafted in a two-step UV-initiated process without the use of a photoinitiator. Surface characterization of the films by attenuated total reflective Fourier transform infrared spectroscopy (ATR-FTIR) and scanning electron microscopy (SEM) suggested successful grafting and conversion of poly(hydroxyethyl acrylate) (PHEA) to PHA chelating moieties from the surface of PET. Colorimetric (ferrozine) and inductively coupled plasma mass spectroscopy (ICP-MS) assays demonstrated the ability of PET-g-PHA to chelate iron in a low-pH (3.0) environment containing a competitive metal chelator (citric acid). Lipid oxidation studies demonstrated the antioxidant activity of PET-g-PHA films in inhibiting iron-promoted oxidation in an acidified oil-in-water (O/W) emulsion model system (pH 3.0). Particle size and ζ-potential analysis indicated that the addition of PET-g-PHA films did not affect the physical stability of the emulsion system. This work suggests that biomimetic chelating moieties can be grafted from PET and effectively inhibit iron-promoted degradation reactions, enabling removal of metal-chelating additives from product formulations.

Natural chelates for radionuclide decorporation

DOEpatents

Premuzic, E.T.

1983-08-25

This invention relates to the method and resulting chelates of desorbing a radionuclide selected from thorium, uranium, and plutonium containing cultures in a bioavailable form involving pseudomonas or other microorganisms. A preferred microorganism is Pseudomonas aeruginosa which forms multiple chelates with thorium in the range of molecular weight 1000 to 1000 and also forms chelates with uranium of molecular weight in the area of 100 to 1000 and 1000 to 2000.

Di-macrocyclic terephthalamide ligands as chelators for the PET radionuclide zirconium-89

DOE PAGES

Pandya, Darpan N.; Pailloux, Sylvie; Tatum, David; ...

2014-12-18

The development of bifunctional chelators (BFCs) which can stably chelate zirconium-89 ((89)Zr) while being conjugated to targeting molecules is an area of active research. Herein we report the first octadentate terephthalamide ligands, which are easily radiolabeled with (89)Zr and are highly stable in vitro. Lastly, they represent a novel class of chelators, which are worthy of further development as BFCs for (89)Zr.

Chelating capture and magnetic removal of non-magnetic heavy metal substances from soil

PubMed Central

Fan, Liren; Song, Jiqing; Bai, Wenbo; Wang, Shengping; Zeng, Ming; Li, Xiaoming; Zhou, Yang; Li, Haifeng; Lu, Haiwei

2016-01-01

A soil remediation method based on magnetic beneficiation is reported. A new magnetic solid chelator powder, FS@IDA (core-shell Fe3O4@SiO2 nanoparticles coated with iminodiacetic acid chelators), was used as a reactive magnetic carrier to selectively capture non-magnetic heavy metals in soil by chelation and removal by magnetic separation. FS@IDA was prepared via inorganic-organic and organic synthesis reactions that generated chelating groups on the surface of magnetic, multi-core, core-shell Fe3O4@SiO2 (FS) nanoparticles. These reactions used a silane coupling agent and sodium chloroacetate. The results show that FS@IDA could chelate the heavy metal component of Cd, Zn, Pb, Cu and Ni carbonates, lead sulfate and lead chloride in water-insoluble salt systems. The resulting FS@IDA-Cd and FS@IDA-Pb chelates could be magnetically separated, resulting in removal rates of approximately 84.9% and 72.2% for Cd and Pb, respectively. FS@IDA could not remove the residual heavy metals and those bound to organic matter in the soil. FS@IDA did not significantly alter the chemical composition of the soil, and it allowed for fast chelating capture, simple magnetic separation and facilitated heavy metal elution. FS@IDA could also be easily prepared and reprocessed. PMID:26878770

Synthetic and natural iron chelators: therapeutic potential and clinical use

PubMed Central

Hatcher, Heather C; Singh, Ravi N; Torti, Frank M; Torti, Suzy V

2013-01-01

Iron-chelation therapy has its origins in the treatment of iron-overload syndromes. For many years, the standard for this purpose has been deferoxamine. Recently, considerable progress has been made in identifying synthetic chelators with improved pharmacologic properties relative to deferoxamine. Most notable are deferasirox (Exjade®) and deferiprone (Ferriprox®), which are now available clinically. In addition to treatment of iron overload, there is an emerging role for iron chelators in the treatment of diseases characterized by oxidative stress, including cardiovascular disease, atherosclerosis, neurodegenerative diseases and cancer. While iron is not regarded as the underlying cause of these diseases, it does play an important role in disease progression, either through promotion of cellular growth and proliferation or through participation in redox reactions that catalyze the formation of reactive oxygen species and increase oxidative stress. Thus, iron chelators may be of therapeutic benefit in many of these conditions. Phytochemicals, many of which bind iron, may also owe some of their beneficial properties to iron chelation. This review will focus on the advances in iron-chelation therapy for the treatment of iron-overload disease and cancer, as well as neurodegenerative and chronic inflammatory diseases. Established and novel iron chelators will be discussed, as well as the emerging role of dietary plant polyphenols that effectively modulate iron biochemistry. PMID:21425984

Chelating capture and magnetic removal of non-magnetic heavy metal substances from soil.

PubMed

Fan, Liren; Song, Jiqing; Bai, Wenbo; Wang, Shengping; Zeng, Ming; Li, Xiaoming; Zhou, Yang; Li, Haifeng; Lu, Haiwei

2016-02-16

A soil remediation method based on magnetic beneficiation is reported. A new magnetic solid chelator powder, FS@IDA (core-shell Fe3O4@SiO2 nanoparticles coated with iminodiacetic acid chelators), was used as a reactive magnetic carrier to selectively capture non-magnetic heavy metals in soil by chelation and removal by magnetic separation. FS@IDA was prepared via inorganic-organic and organic synthesis reactions that generated chelating groups on the surface of magnetic, multi-core, core-shell Fe3O4@SiO2 (FS) nanoparticles. These reactions used a silane coupling agent and sodium chloroacetate. The results show that FS@IDA could chelate the heavy metal component of Cd, Zn, Pb, Cu and Ni carbonates, lead sulfate and lead chloride in water-insoluble salt systems. The resulting FS@IDA-Cd and FS@IDA-Pb chelates could be magnetically separated, resulting in removal rates of approximately 84.9% and 72.2% for Cd and Pb, respectively. FS@IDA could not remove the residual heavy metals and those bound to organic matter in the soil. FS@IDA did not significantly alter the chemical composition of the soil, and it allowed for fast chelating capture, simple magnetic separation and facilitated heavy metal elution. FS@IDA could also be easily prepared and reprocessed.

Chelating capture and magnetic removal of non-magnetic heavy metal substances from soil

NASA Astrophysics Data System (ADS)

Fan, Liren; Song, Jiqing; Bai, Wenbo; Wang, Shengping; Zeng, Ming; Li, Xiaoming; Zhou, Yang; Li, Haifeng; Lu, Haiwei

2016-02-01

A soil remediation method based on magnetic beneficiation is reported. A new magnetic solid chelator powder, FS@IDA (core-shell Fe3O4@SiO2 nanoparticles coated with iminodiacetic acid chelators), was used as a reactive magnetic carrier to selectively capture non-magnetic heavy metals in soil by chelation and removal by magnetic separation. FS@IDA was prepared via inorganic-organic and organic synthesis reactions that generated chelating groups on the surface of magnetic, multi-core, core-shell Fe3O4@SiO2 (FS) nanoparticles. These reactions used a silane coupling agent and sodium chloroacetate. The results show that FS@IDA could chelate the heavy metal component of Cd, Zn, Pb, Cu and Ni carbonates, lead sulfate and lead chloride in water-insoluble salt systems. The resulting FS@IDA-Cd and FS@IDA-Pb chelates could be magnetically separated, resulting in removal rates of approximately 84.9% and 72.2% for Cd and Pb, respectively. FS@IDA could not remove the residual heavy metals and those bound to organic matter in the soil. FS@IDA did not significantly alter the chemical composition of the soil, and it allowed for fast chelating capture, simple magnetic separation and facilitated heavy metal elution. FS@IDA could also be easily prepared and reprocessed.

Physics of a novel magnetic resonance and electrical impedance combination for breast cancer diagnosis

NASA Astrophysics Data System (ADS)

Kallergi, Maria; Heine, John J.; Wollin, Ernest

2015-03-01

A new technique is proposed and experimentally validated for breast cancer detection and diagnosis. The technique combines magnetic resonance with electrical impedance measurements and has the potential to increase the specificity of magnetic resonance mammography (MRM) thereby reducing false positive biopsy rates. The new magnetic resonance electrical impedance mammography (MREIM) adds a time varying electric field during a supplementary sequence to a standard MRM examination with an apparatus that is "invisible" to the patient. The applied electric field produces a current that creates an additional magnetic field with a component aligned with the bore magnetic field that can alter the native signal in areas of higher electrical conductivity. The justification for adding the electric field is that the electrical conductivity of cancerous breast tissue is approximately 3-40 times higher than normal breast tissue and, hence, conductivity of malignant tissue represents a known clinical disease biomarker. In a pilot study with custom-made phantoms and experimental protocols, it was demonstrated that MREIM can produce, as theoretically predicted, a detectable differential signal in areas of higher electrical conductivity (tumor surrogate regions); the evidence indicates that the differential signal is produced by the confluence of two different effects at full image resolution without gadolinium chelate contrast agent injection, without extraneous reconstruction techniques, and without cumbersome multi-positioned patient electrode configurations. This paper describes the theoretical model that predicts and explains the observed experimental results that were also confirmed by simulation studies.

Highly stabilized gadolinium chelates functionalized on metal nanoparticles as magnetic resonance imaging contrast agent

NASA Astrophysics Data System (ADS)

Siddiqui, Talha S.

Magnetic resonance imaging (MRI) is a non-invasive method for imaging and diagnosing tissue damage, organ function and the vascular system. Magnevist(TM) a complex of diethylenetriaminepentaacetic acid (DTPA) and Gd3+ is a clinically approved contrast agent for MRI. A derivative of DTPA was formed by the addition of two cysteine groups (DTPA-L-Cys) through amide linkage. The Gd complex of this ligand bonds with the silver surfaces through the cysteine thiols. GdDTPA-L-Cys was bound to ˜10nm diameter Ag nanoparticles for use as a multifunctional MRI contrast agent. The ligand and complex were characterized by 1H and 13C NMR, ESI-MS and IR spectroscopy. The silver construct was characterized by TEM, TGA and UV-Vis absorption spectra. The per metal complex r1 relaxivity of GdDTPA-L-Cys{Ag} greater than that of Magnavist(TM) with the same molarity for both compounds. The synthesis of a DTPA derivative is described that allows it to bind to silver or gold nanoparticles through a single thiol linkage (DTPASH). The resulting Gd complex, GdDTPASH, was bound to Ag nanoparticles to create a single monolayer on the surface. The construct was further stabilized in buffered solution with the addition of a thiolated PEG chain. The highly stabilized nanoparticle construct delivers a high payload of Gd compelex and is an effective T1 brightening agent. The production of this type of construct opens the way for engineered multimodal MRI contrast agents.

An albumin-based theranostic nano-agent for dual-modal imaging guided photothermal therapy to inhibit lymphatic metastasis of cancer post surgery.

PubMed

Chen, Qian; Liang, Chao; Wang, Xin; He, Jingkang; Li, Yonggang; Liu, Zhuang

2014-11-01

A large variety of cancers are associated with a high incidence of lymph node metastasis, which leads to a high risk of cancer death. Herein, we demonstrate that multimodal imaging guided photothermal therapy can inhibit tumor metastasis after surgery by burning the sentinel lymph nodes (SLNs) with metastatic tumor cells. A near-infrared dye, IR825, is absorbed onto human serum albumin (HSA), which is covalently linked with diethylenetriamine pentaacetic acid (DTPA) molecules to chelate gadolinium. The formed HSA-Gd-IR825 nanocomplex exhibits strong fluorescence together with high near-infrared (NIR) absorbance, and in the mean time could serve as a T1 contrast agent in magnetic resonance (MR) imaging. In vivo bi-modal fluorescence and MR imaging uncovers that HSA-Gd-IR825 after being injected into the primary tumor would quickly migrate into tumor-associated SLNs through lymphatic circulation. Utilizing the strong NIR absorbance of HSA-Gd-IR825, SLNs with metastatic cancer cells can be effectively ablated under exposure to a NIR laser. Such treatment when combined with surgery to remove the primary tumor offers remarkable therapeutic outcomes in greatly inhibiting further metastatic spread of cancer cells and prolonging animal survival. Our work presents an albumin-based theranostic nano-probe with functions of multimodal imaging and photothermal therapy, together with a 'photothermal ablation assisted surgery' strategy, promising for future clinical cancer treatment. Copyright © 2014 Elsevier Ltd. All rights reserved.

Use of gadolinium chloride as a contrast agent for imaging spruce knots by magnetic resonance

Treesearch

Thomas L. Eberhardt; Chi-Leung So; Amy H. Herlihy; Po-Wah So

2006-01-01

Treatments of knot-containing spruce wood blocks with a paramagnetic salt, gadolinium (III) chloride, in combination with solvent pretreatments, were evaluated as strategies to enhance the visualization of wood features by magnetic resonance imaging (MRI). Initial experiments with clear wood and excised knot samples showed differences in moisture uptake after...

CONTROL ROD FOR A NUCLEAR REACTOR AND METHOD OF PREPARATION

DOEpatents

Hausner, H.H.

1958-12-30

BS>An improved control rod is presented for a nuclear reactor. This control rod is comprised of a rare earth metal oxide or rare earth metal carbide such as gadolinium oxide or gadolinium carbide, uniformly distributed in a metal matrix having a low cross sectional area of absorption for thermal neutrons, such as aluminum, beryllium, and zirconium.

Layered gadolinium hydroxides for low-temperature magnetic cooling.

PubMed

Abellán, Gonzalo; Espallargas, Guillermo Mínguez; Lorusso, Giulia; Evangelisti, Marco; Coronado, Eugenio

2015-09-28

Layered gadolinium hydroxides have revealed to be excellent candidates for cryogenic magnetic refrigeration. These materials behave as pure 2D magnetic systems with a Heisenberg-Ising critical crossover, induced by dipolar interactions. This 2D character and the possibility offered by these materials to be delaminated open the possibility of rapid heat dissipation upon substrate deposition.

Rapid colorimetric sensing of gadolinium by EGCG-derived AgNPs: the development of a nanohybrid bioimaging probe.

PubMed

Singh, Rohit Kumar; Mishra, Sourav; Jena, Satyapriya; Panigrahi, Bijayananda; Das, Bhaskar; Jayabalan, Rasu; Parhi, Pankaj Kumar; Mandal, Dindyal

2018-04-17

Polyphenol functionalized silver nanoparticles (AgNPs) have been developed and demonstrated as colorimetric sensors for the selective detection of gadolinium. The newly obtained AgNP-Gd3+ conjugates exhibit high aqueous dispersibility and excitation dependent fluorescence emission. The conjugates offer multicolor bioimaging potential owing to their excellent luminescence properties.

Neutron Absorbing Alloys

DOEpatents

Mizia, Ronald E.; Shaber, Eric L.; DuPont, John N.; Robino, Charles V.; Williams, David B.

2004-05-04

The present invention is drawn to new classes of advanced neutron absorbing structural materials for use in spent nuclear fuel applications requiring structural strength, weldability, and long term corrosion resistance. Particularly, an austenitic stainless steel alloy containing gadolinium and less than 5% of a ferrite content is disclosed. Additionally, a nickel-based alloy containing gadolinium and greater than 50% nickel is also disclosed.

Transfusional iron overload and iron chelation therapy in thalassemia major and sickle cell disease.

PubMed

Marsella, Maria; Borgna-Pignatti, Caterina

2014-08-01

Iron overload is an inevitable consequence of blood transfusions and is often accompanied by increased iron absorption from the gut. Chelation therapy is necessary to prevent the consequences of hemosiderosis. Three chelators, deferoxamine, deferiprone, and deferasirox, are presently available and a fourth is undergoing clinical trials. The efficacy of all 3 available chelators has been demonstrated. Also, many studies have shown the efficacy of the combination of deferoxamine plus deferiprone as an intensive treatment of severe iron overload. Alternating chelators can reduce adverse effects and improve compliance. Adherence to therapy is crucial for good results. Copyright © 2014 Elsevier Inc. All rights reserved.

Supercritical fluid extraction

DOEpatents

Wai, Chien M.; Laintz, Kenneth

1994-01-01

A method of extracting metalloid and metal species from a solid or liquid material by exposing the material to a supercritical fluid solvent containing a chelating agent. The chelating agent forms chelates that are soluble in the supercritical fluid to allow removal of the species from the material. In preferred embodiments, the extraction solvent is supercritical carbon dioxide and the chelating agent is a fluorinated or lipophilic crown ether or fluorinated dithiocarbamate. The method provides an environmentally benign process for removing contaminants from industrial waste without using acids or biologically harmful solvents. The chelate and supercritical fluid can be regenerated, and the contaminant species recovered, to provide an economic, efficient process.

Metal regeneration of iron chelates in nitric oxide scrubbing

DOEpatents

Chang, Shih-Ger; Littlejohn, David; Shi, Yao

1997-08-19

The present invention relates to a process of using metal particles to reduce NO to NH.sub.3. More specifically, the invention concerns an improved process to regenerate iron (II) (CHELATE) by reduction of iron (II) (CHELATE) (NO) complex, which process comprises: a) contacting an aqueous solution containing iron (II) (CHELATE) (NO) with metal particles at between about 20.degree. and 90.degree. C. to reduce NO present, produce ammonia or an ammonium ion, and produce free iron (II) (CHELATE) at a pH of between about 3 and 8. The process is useful to remove NO from flue gas and reduce pollution.

Metal regeneration of iron chelates in nitric oxide scrubbing

DOEpatents

Chang, S.G.; Littlejohn, D.; Shi, Y.

1997-08-19

The present invention relates to a process of using metal particles to reduce NO to NH{sub 3}. More specifically, the invention concerns an improved process to regenerate iron (II) (CHELATE) by reduction of iron (II) (CHELATE) (NO) complex, which process comprises: (a) contacting an aqueous solution containing iron (II) (CHELATE) (NO) with metal particles at between about 20 and 90 C to reduce NO present, produce ammonia or an ammonium ion, and produce free iron (II) (CHELATE) at a pH of between about 3 and 8. The process is useful to remove NO from flue gas and reduce pollution. 34 figs.

[Gadolinium-based contrast agents for magnetic resonance imaging].

PubMed

Carrasco Muñoz, S; Calles Blanco, C; Marcin, Javier; Fernández Álvarez, C; Lafuente Martínez, J

2014-06-01

Gadolinium-based contrast agents are increasingly being used in magnetic resonance imaging. These agents can improve the contrast in images and provide information about function and metabolism, increasing both sensitivity and specificity. We describe the gadolinium-based contrast agents that have been approved for clinical use, detailing their main characteristics based on their chemical structure, stability, and safety. In general terms, these compounds are safe. Nevertheless, adverse reactions, the possibility of nephrotoxicity from these compounds, and the possibility of developing nephrogenic systemic fibrosis will be covered in this article. Lastly, the article will discuss the current guidelines, recommendations, and contraindications for their clinical use, including the management of pregnant and breast-feeding patients. Copyright © 2014 SERAM. Published by Elsevier Espana. All rights reserved.

Gadolinium-based nanoparticles for highly efficient T1-weighted magnetic resonance imaging

NASA Astrophysics Data System (ADS)

Lim, Eun-Kyung; Kang, Byunghoon; Choi, Yuna; Jang, Eunji; Han, Seungmin; Lee, Kwangyeol; Suh, Jin-Suck; Haam, Seungjoo; Huh, Yong-Min

2014-06-01

We developed Pyrene-Gadolinium (Py-Gd) nanoparticles as pH-sensitive magnetic resonance imaging (MRI) contrast agents capable of showing a high-Mr signal in cancer-specific environments, such as acidic conditions. Py-Gd nanoparticles were prepared by coating Py-Gd, which is a complex of gadolinium with pyrenyl molecules, with pyrenyl polyethyleneglycol PEG using a nano-emulsion method. These particles show better longitudinal relaxation time (T1) MR signals in acidic conditions than they do in neutral conditions. Furthermore, the particles exhibit biocompatibility and MR contrast effects in both in vitro and in vivo studies. From these results, we confirm that Py-Gd nanoparticles have the potential to be applied for accurate cancer diagnosis and therapy.

The evolution of gadolinium based contrast agents: from single-modality to multi-modality

NASA Astrophysics Data System (ADS)

Zhang, Li; Liu, Ruiqing; Peng, Hui; Li, Penghui; Xu, Zushun; Whittaker, Andrew K.

2016-05-01

Gadolinium-based contrast agents are extensively used as magnetic resonance imaging (MRI) contrast agents due to their outstanding signal enhancement and ease of chemical modification. However, it is increasingly recognized that information obtained from single modal molecular imaging cannot satisfy the higher requirements on the efficiency and accuracy for clinical diagnosis and medical research, due to its limitation and default rooted in single molecular imaging technique itself. To compensate for the deficiencies of single function magnetic resonance imaging contrast agents, the combination of multi-modality imaging has turned to be the research hotpot in recent years. This review presents an overview on the recent developments of the functionalization of gadolinium-based contrast agents, and their application in biomedicine applications.

Metal Pollutants and Cardiovascular Disease: Mechanisms and Consequences of Exposure

PubMed Central

Solenkova, Natalia V.; Newman, Jonathan D.; Berger, Jeffrey S.; Thurston, George; Hochman, Judith S.; Lamas, Gervasio A.

2014-01-01

Introduction There is epidemiological evidence that metal contaminants may play a role in the development of atherosclerosis and its complications. Moreover, a recent clinical trial of a metal chelator had a surprisingly positive result in reducing cardiovascular events in a secondary prevention population, strengthening the link between metal exposure and cardiovascular disease (CVD). This is, therefore, an opportune moment to review evidence that exposure to metal pollutants, such as arsenic, lead, cadmium, and mercury, are significant risk factors for CVD. Methods We reviewed the English-speaking medical literature to assess and present the epidemiological evidence that 4 metals having no role in the human body (xenobiotic), mercury, lead, cadmium, and arsenic, have epidemiologic and mechanistic links to atherosclerosis and CVD. Moreover, we briefly review how the results of the Trial to Assess Chelation Therapy strengthen the link between atherosclerosis and xenobiotic metal contamination in humans. Conclusions There is strong evidence that xenobiotic metal contamination is linked to atherosclerotic disease and is a modifiable risk factor. PMID:25458643

Development of an iron chelating polyethylene film for active packaging applications.

PubMed

Tian, Fang; Decker, Eric A; Goddard, Julie M

2012-02-29

Metal-promoted oxidation reactions are a major cause of food quality deterioration. Active packaging offers novel approaches to controlling such oxidation for the purpose of extending shelf life. Herein, we report modification of the surface of polyethylene (PE) films to possess metal chelating activity. Metal chelating carboxylic acids were introduced to the film surface using cross-linking agents [polyethylenimine (PEI) or ethylenediamine (ED)] to increase the number of available carboxylic acids. ATR-FTIR, contact angle, dye assay, and iron chelating assay were used to characterize changes in surface chemistry after each functionalization step. The chelator poly(acrylic acid) (PAA) was attached to the surface at a density of 9.12 ± 0.71 nmol carboxyl groups/cm², and exhibited an iron chelating activity. The results indicate that PAA-modified PE films might have a higher affinity to Fe³⁺ than Fe²⁺ with the optimum binding pH at 5.0. Such inexpensive active packaging materials are promising in food industry for the preservation of liquid and semiliquid food products and have application in heavy metal chelation therapy for biomedical materials as well.

Europium-doped gadolinium sulfide nanoparticles as a dual-mode imaging agent for T1-weighted MR and photoluminescence imaging.

PubMed

Jung, Jongjin; Kim, Mi Ae; Cho, Jee-Hyun; Lee, Seung Jae; Yang, Ilseung; Cho, Janggeun; Kim, Seong Keun; Lee, Chulhyun; Park, Joung Kyu

2012-08-01

We present a facile synthesis of europium-doped gadolinium sulfide (GdS:Eu(3+)) opto-magnetic nanoparticles (NPs) via sonochemistry. Their photoluminescence and strong paramagnetic properties enable these NPs to be utilized as an in vitro cell imaging and in vivo T(1)-weighted MR imaging probe. The GdS:Eu(3+) NPs have a prominent longitudinal (r(1)) relaxivity value, which is a critical parameter for T(1)-weighted MR imaging. Here, we showed not only their strong positive contrast effect to blood vessels and organs of mice, but also blood half-life and biodistribution including clearance from organs, in order to assess the GdS:Eu(3+) NPs as a competent nanocrystal-based T(1) contrast agent. We further showed confocal images of breast cancer cells containing GdS:Eu(3+) NPs to evaluate as a photoluminescence probe. Dual-mode imaging capability obtained from the GdS:Eu(3+) NPs will allow target-oriented cellular imaging as well as the resulting disease-specific MR imaging. Copyright © 2012 Elsevier Ltd. All rights reserved.

Extracting metals directly from metal oxides

DOEpatents

Wai, Chien M.; Smart, Neil G.; Phelps, Cindy

1997-01-01

A method of extracting metals directly from metal oxides by exposing the oxide to a supercritical fluid solvent containing a chelating agent is described. Preferably, the metal is an actinide or a lanthanide. More preferably, the metal is uranium, thorium or plutonium. The chelating agent forms chelates that are soluble in the supercritical fluid, thereby allowing direct removal of the metal from the metal oxide. In preferred embodiments, the extraction solvent is supercritical carbon dioxide and the chelating agent is selected from the group consisting of .beta.-diketones, halogenated .beta.-diketones, phosphinic acids, halogenated phosphinic acids, carboxylic acids, halogenated carboxylic acids, and mixtures thereof. In especially preferred embodiments, at least one of the chelating agents is fluorinated. The method provides an environmentally benign process for removing metals from metal oxides without using acids or biologically harmful solvents. The chelate and supercritical fluid can be regenerated, and the metal recovered, to provide an economic, efficient process.

Extracting metals directly from metal oxides

DOEpatents

Wai, C.M.; Smart, N.G.; Phelps, C.

1997-02-25

A method of extracting metals directly from metal oxides by exposing the oxide to a supercritical fluid solvent containing a chelating agent is described. Preferably, the metal is an actinide or a lanthanide. More preferably, the metal is uranium, thorium or plutonium. The chelating agent forms chelates that are soluble in the supercritical fluid, thereby allowing direct removal of the metal from the metal oxide. In preferred embodiments, the extraction solvent is supercritical carbon dioxide and the chelating agent is selected from the group consisting of {beta}-diketones, halogenated {beta}-diketones, phosphinic acids, halogenated phosphinic acids, carboxylic acids, halogenated carboxylic acids, and mixtures thereof. In especially preferred embodiments, at least one of the chelating agents is fluorinated. The method provides an environmentally benign process for removing metals from metal oxides without using acids or biologically harmful solvents. The chelate and supercritical fluid can be regenerated, and the metal recovered, to provide an economic, efficient process. 4 figs.

Method for separating metal chelates from other materials based on solubilities in supercritical fluids

DOEpatents

Wai, Chien M.; Smart, Neil G.; Phelps, Cindy

2001-01-01

A method for separating a desired metal or metalloi from impurities using a supercritical extraction process based on solubility differences between the components, as well as the ability to vary the solvent power of the supercritical fluid, is described. The use of adduct-forming agents, such as phosphorous-containing ligands, to separate metal or metalloid chelates in such processes is further disclosed. In preferred embodiments, the extraction solvent is supercritical carbon dioxide and the chelating agent is selected from the group consisting of .beta.-diketones; phosphine oxides, such as trialkylphosphine oxides, triarylphosphine oxides and alkylarylphosphine oxides; phosphinic acids; carboxylic acids; phosphates, such as trialkylphosphates, triarylphosphates and alkylarylphosphates; crown ethers; dithiocarbamates; phosphine sulfides; phosphorothioic acids; thiophosphinic acids; halogenated analogs of these chelating agents; and mixtures of these chelating agents. In especially preferred embodiments, at least one of the chelating agents is fluorinated.

A review of pitfalls and progress in chelation treatment of metal poisonings.

PubMed

Andersen, Ole; Aaseth, Jan

2016-12-01

Most acute and chronic human metal poisonings are due to oral or inhalation exposure. Almost 80% of published animal experiments on chelation in metal poisoning used single or repeated intraperitoneal, intramuscular or intravenous administration of metal and chelator, impeding extrapolation to clinical settings. Intramuscular administration of dimercaptopropanol (BAL) has until now been used in acute arsenic, lead, and mercury poisonings, but repeated BAL administration increased the brain uptake of As, Pb and Hg in experimental animals. Also, diethyl dithiocarbamate (DDC) has been used as antidote in acute experimental animal parenteral Cd poisoning, and both DDC and tetraethylthiuram disulfide (TTD, disulfiram, Antabuse) have been used in nickel allergic patients. However, even one dose of DDC given immediately after oral Cd or Ni increased their brain uptake considerably. The calcium salt of ethylenediamminetetraacetic acid (CaEDTA) but not dimercaptosuccinic acid (DMSA) increased the brain uptake of Pb. In oral Cd or Hg poisoning, early oral administration of DMSA or dimercaptopropane sulfonate (DMPS) increased survival and reduced intestinal metal uptake. Oral administration of Prussian Blue or resins with fixed chelating groups that are not absorbed offer chelation approaches for decorporation after oral exposure to various metals. Diethylenetriaminepentaacetic acid (DTPA) nebulizers for pulmonary chelation after inhalation exposure need further development. Also, combined chelation with more than one compound may offer extensive advances. Solid knowledge on the chemistry of metal chelates together with relevant animal experiments should guide development of chelation procedures to alleviate and not aggravate the clinical status of poisoned patients. Copyright © 2016 Elsevier GmbH. All rights reserved.

Biological and Clinical Aspects of Lanthanide Coordination Compounds

PubMed Central

Misra, Sudhindra N.; M., Indira Devi; Shukla, Ram S.

2004-01-01

The coordinating chemistry of lanthanides, relevant to the biological, biochemical and medical aspects, makes a significant contribution to understanding the basis of application of lanthanides, particularly in biological and medical systems. The importance of the applications of lanthanides, as an excellent diagnostic and prognostic probe in clinical diagnostics, and an anticancer material, is remarkably increasing. Lanthanide complexes based X-ray contrast imaging and lanthanide chelates based contrast enhancing agents for magnetic resonance imaging (MRI) are being excessively used in radiological analysis in our body systems. The most important property of the chelating agents, in lanthanide chelate complex, is its ability to alter the behaviour of lanthanide ion with which it binds in biological systems, and the chelation markedly modifies the biodistribution and excretion profile of the lanthanide ions. The chelating agents, especially aminopoly carboxylic acids, being hydrophilic, increase the proportion of their complex excreted from complexed lanthanide ion form biological systems. Lanthanide polyamino carboxylate-chelate complexes are used as contrast enhancing agents for Magnetic Resonance Imaging. Conjugation of antibodies and other tissue specific molecules to lanthanide chelates has led to a new type of specific MRI contrast agents and their conjugated MRI contrast agents with improved relaxivity, functioning in the body similar to drugs. Many specific features of contrast agent assisted MRI make it particularly effective for musculoskeletal and cerebrospinal imaging. Lanthanide-chelate contrast agents are effectively used in clinical diagnostic investigations involving cerebrospinal diseases and in evaluation of central nervous system. Chelated lanthanide complexes shift reagent aided 23Na NMR spectroscopic analysis is used in cellular, tissue and whole organ systems. PMID:18365075

Clickable, hydrophilic ligand for fac-[M(I)(CO)3](+) (M = Re/(99m)Tc) applied in an S-functionalized α-MSH peptide.

PubMed

Kasten, Benjamin B; Ma, Xiaowei; Liu, Hongguang; Hayes, Thomas R; Barnes, Charles L; Qi, Shibo; Cheng, Kai; Bottorff, Shalina C; Slocumb, Winston S; Wang, Jing; Cheng, Zhen; Benny, Paul D

2014-03-19

The copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) click reaction was used to incorporate alkyne-functionalized dipicolylamine (DPA) ligands (1 and 3) for fac-[M(I)(CO)3](+) (M = Re/(99m)Tc) complexation into an α-melanocyte stimulating hormone (α-MSH) peptide analogue. A novel DPA ligand with carboxylate substitutions on the pyridyl rings (3) was designed to increase the hydrophilicity and to decrease in vivo hepatobiliary retention of fac-[(99m)Tc(I)(CO)3](+) complexes used in single photon emission computed tomography (SPECT) imaging studies with targeting biomolecules. The fac-[Re(I)(CO)3(3)] complex (4) was used for chemical characterization and X-ray crystal analysis prior to radiolabeling studies between 3 and fac-[(99m)Tc(I)(OH2)3(CO)3](+). The corresponding (99m)Tc complex (4a) was obtained in high radiochemical yields, was stable in vitro for 24 h during amino acid challenge and serum stability assays, and showed increased hydrophilicity by log P analysis compared to an analogous complex with nonfunctionalized pyridine rings (2a). An α-MSH peptide functionalized with an azide was labeled with fac-[M(I)(CO)3](+) using both click, then chelate (CuAAC reaction with 1 or 3 followed by metal complexation) and chelate, then click (metal complexation of 1 and 3 followed by CuAAC with the peptide) strategies to assess the effects of CuAAC conditions on fac-[M(I)(CO)3](+) complexation within a peptide framework. The peptides from the click, then chelate strategy had different HPLC tR's and in vitro stabilities compared to those from the chelate, then click strategy, suggesting nonspecific coordination of fac-[M(I)(CO)3](+) using this synthetic route. The fac-[M(I)(CO)3](+)-complexed peptides from the chelate, then click strategy showed >90% stability during in vitro challenge conditions for 6 h, demonstrated high affinity and specificity for the melanocortin 1 receptor (MC1R) in IC50 analyses, and led to moderately high uptake in B16F10 melanoma cells. Log P analysis of the (99m)Tc-labeled peptides confirmed the enhanced hydrophilicity of the peptide bearing the novel, carboxylate-functionalized DPA chelate (10a') compared to the peptide with the unmodified DPA chelate (9a'). In vivo biodistribution analysis of 9a' and 10a' showed moderate tumor uptake in a B16F10 melanoma xenograft mouse model with enhanced renal uptake and surprising intestinal uptake for 10a' compared to predominantly hepatic accumulation for 9a'. These results, coupled with the versatility of CuAAC, suggests this novel, hydrophilic chelate can be incorporated into numerous biomolecules containing azides for generating targeted fac-[M(I)(CO)3](+) complexes in future studies.

The Extracellular Domain of Human High Affinity Copper Transporter (hNdCTR1), Synthesized by E. coli Cells, Chelates Silver and Copper Ions In Vivo

PubMed Central

Sankova, Tatiana P.; Orlov, Iurii A.; Saveliev, Andrey N.; Kirilenko, Demid A.; Babich, Polina S.; Brunkov, Pavel N.; Puchkova, Ludmila V.

2017-01-01

There is much interest in effective copper chelators to correct copper dyshomeostasis in neurodegenerative and oncological diseases. In this study, a recombinant fusion protein for expression in Escherichia coli cells was constructed from glutathione-S-transferase (GST) and the N-terminal domain (ectodomain) of human high affinity copper transporter CTR1 (hNdCTR1), which has three metal-bound motifs. Several biological properties of the GST-hNdCTR1 fusion protein were assessed. It was demonstrated that in cells, the protein was prone to oligomerization, formed inclusion bodies and displayed no toxicity. Treatment of E. coli cells with copper and silver ions reduced cell viability in a dose- and time-dependent manner. Cells expressing GST-hNdCTR1 protein demonstrated resistance to the metal treatments. These cells accumulated silver ions and formed nanoparticles that contained AgCl and metallic silver. In this bacterial population, filamentous bacteria with a length of about 10 µm were often observed. The possibility for the fusion protein carrying extracellular metal binding motifs to integrate into the cell’s copper metabolism and its chelating properties are discussed. PMID:29099786

The Extracellular Domain of Human High Affinity Copper Transporter (hNdCTR1), Synthesized by E. coli Cells, Chelates Silver and Copper Ions In Vivo.

PubMed

Sankova, Tatiana P; Orlov, Iurii A; Saveliev, Andrey N; Kirilenko, Demid A; Babich, Polina S; Brunkov, Pavel N; Puchkova, Ludmila V

2017-11-03

There is much interest in effective copper chelators to correct copper dyshomeostasis in neurodegenerative and oncological diseases. In this study, a recombinant fusion protein for expression in Escherichia coli cells was constructed from glutathione-S-transferase (GST) and the N-terminal domain (ectodomain) of human high affinity copper transporter CTR1 (hNdCTR1), which has three metal-bound motifs. Several biological properties of the GST-hNdCTR1 fusion protein were assessed. It was demonstrated that in cells, the protein was prone to oligomerization, formed inclusion bodies and displayed no toxicity. Treatment of E. coli cells with copper and silver ions reduced cell viability in a dose- and time-dependent manner. Cells expressing GST-hNdCTR1 protein demonstrated resistance to the metal treatments. These cells accumulated silver ions and formed nanoparticles that contained AgCl and metallic silver. In this bacterial population, filamentous bacteria with a length of about 10 µm were often observed. The possibility for the fusion protein carrying extracellular metal binding motifs to integrate into the cell's copper metabolism and its chelating properties are discussed.

Computational Assessment of Potassium and Magnesium Ion Binding to a Buried Pocket in GTPase-Associating Center RNA

PubMed Central

2016-01-01

An experimentally well-studied model of RNA tertiary structures is a 58mer rRNA fragment, known as GTPase-associating center (GAC) RNA, in which a highly negative pocket walled by phosphate oxygen atoms is stabilized by a chelated cation. Although such deep pockets with more than one direct phosphate to ion chelation site normally include magnesium, as shown in one GAC crystal structure, another GAC crystal structure and solution experiments suggest potassium at this site. Both crystal structures also depict two magnesium ions directly bound to the phosphate groups comprising this controversial pocket. Here, we used classical molecular dynamics simulations as well as umbrella sampling to investigate the possibility of binding of potassium versus magnesium inside the pocket and to better characterize the chelation of one of the binding magnesium ions outside the pocket. The results support the preference of the pocket to accommodate potassium rather than magnesium and suggest that one of the closely binding magnesium ions can only bind at high magnesium concentrations, such as might be present during crystallization. This work illustrates the complementary utility of molecular modeling approaches with atomic-level detail in resolving discrepancies between conflicting experimental results. PMID:27983843

Computational Assessment of Potassium and Magnesium Ion Binding to a Buried Pocket in GTPase-Associating Center RNA.

PubMed

Hayatshahi, Hamed S; Roe, Daniel R; Galindo-Murillo, Rodrigo; Hall, Kathleen B; Cheatham, Thomas E

2017-01-26

An experimentally well-studied model of RNA tertiary structures is a 58mer rRNA fragment, known as GTPase-associating center (GAC) RNA, in which a highly negative pocket walled by phosphate oxygen atoms is stabilized by a chelated cation. Although such deep pockets with more than one direct phosphate to ion chelation site normally include magnesium, as shown in one GAC crystal structure, another GAC crystal structure and solution experiments suggest potassium at this site. Both crystal structures also depict two magnesium ions directly bound to the phosphate groups comprising this controversial pocket. Here, we used classical molecular dynamics simulations as well as umbrella sampling to investigate the possibility of binding of potassium versus magnesium inside the pocket and to better characterize the chelation of one of the binding magnesium ions outside the pocket. The results support the preference of the pocket to accommodate potassium rather than magnesium and suggest that one of the closely binding magnesium ions can only bind at high magnesium concentrations, such as might be present during crystallization. This work illustrates the complementary utility of molecular modeling approaches with atomic-level detail in resolving discrepancies between conflicting experimental results.

Hypersensitivity reaction with deferasirox

PubMed Central

Sharma, Atul; Arora, Ekta; Singh, Harmanjit

2015-01-01

Thalassemias comprise a group of hereditary blood disorders. Thalassemia major presents with anemia within the first 2 years of life requiring frequent blood transfusions for sustaining life. Regular blood transfusions lead to iron overload-related complications. Prognosis of thalassemia has improved because of the availability of iron-chelating agents. Oral iron chelators are the mainstay of chelation therapy. Deferasirox is a new-generation oral iron chelator for once daily usage. We herein describe a patient of beta thalassemia major who developed an allergic manifestation in the form of erythematous pruritic skin rashes to the oral iron chelator deferasirox. This is a rare adverse reaction reported with deferasirox that led to a therapeutic dilemma in this particular case. PMID:25969661

Investigation of Magnetostatic Surface Waves for Anisotropic Effects.

DTIC Science & Technology

1986-06-01

inves- tigate the effect of launching magnetostatic surface waves at different angles on a yttrium-iron- garnet (YIG) single crystal film . Many...propagation indeed could be achieved on a YIG thin film ring grown on a gadolinium-gallium- garnet (GGG) substrate (Sethares, 1975) (see Figure 1.1). The use of...thin films grown on a gadolinium-gallium- garnet substrate. The films were 27

Gadolinium chloride as a contrast agent for imaging wood composite components by magnetic resonance

Treesearch

Thomas L. Eberhardt; Chi-Leung So; Andrea Protti; Po-Wah So

2009-01-01

Although paramagnetic contrast agents have an established track record in medical uses of magnetic resonance imaging (MRI), only recently has a contrast agent been used for enhancing MRI images of solid wood specimens. Expanding on this concept, wood veneers were treated with a gadolinium-based contrast agent and used in a model system comprising three-ply plywood...

An Integrated Rare Earth Elements Supply Chain Strategy

DTIC Science & Technology

2011-02-24

iron boron magnets in Joint Direct Attack Munitions (JDAM) smart bombs; neodymium-yttrium- aluminum - garnet lasers and range finders in multiple weapon...components Europium 63 computer screens, fluorescent lights Gadolinium 64 magnetic applications, phosphors Terbium 65 phosphors, projection TV’s...Defense Stockpile report advised several production delays of weapons systems were caused by lanthanum, cerium, europium and gadolinium supply

Evaluation of on-line chelant addition to PWR steam generators. Steam generator cleaning project

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tvedt, T.J.; Wallace, S.L.; Griffin, F. Jr.

1983-09-01

The investigation of chelating agents for continuous water treatment of secondary loops of PWR steam generators were conducted in two general areas: the study of the chemistry of chelating agents and the study of materials compatability with chelating agents. The thermostability of both EDTA and HEDTA metal chelates in All Volatile Treatment (AVT) water chemistry were shown to be greater than or equal to the thermostability of EDTA metal chelates in phosphate-sulfite water chemistry. HEDTA metal chelates were shown to have a much greater stability than EDTA metal chelates. Using samples taken from the EDTA metal chelate thermostability study andmore » from the Commonwealth Research Corporation (CRC) model steam generators (MSG), EDTA decomposition products were determined. Active metal surfaces were shown to become passivated when exposed to EDTA and HEDTA concentrations as high as 0.1% w/w in AVT. Trace amounts of iron in the water were found to increase the rate of passivation. Material balance and visual inspection data from CRC model steam generators showed that metal was transported through and cleaned from the MSG's. The Inconel 600 tubes of the salt water fouled model steam generators experienced pitting corrosion. Results of this study demonstrates the feasibility of EDTA as an on-line water treatment additive to maintain nuclear steam generators in a clean condition.« less

Enhancement effects of chelating agents on the degradation of tetrachloroethene in Fe(III) catalyzed percarbonate system

PubMed Central

Miao, Zhouwei; Gu, Xiaogang; Lu, Shuguang; Brusseau, Mark L.; Zhang, Xiang; Fu, Xiaori; Danish, Muhammad; Qiu, Zhaofu; Sui, Qian

2015-01-01

The performance of Fe(III)-based catalyzed sodium percarbonate (SPC) for stimulating the oxidation of tetrachloroethene (PCE) for groundwater remediation applications was investigated. The chelating agents citric acid monohydrate (CIT), oxalic acid (OA), and Glutamic acid (Glu) significantly enhanced the degradation of PCE. Conversely, ethylenediaminetetraacetic acid (EDTA) had a negative impact on PCE degradation, which may due to its strong Fe chelation and HO• scavenging abilities. However, excessive SPC or chelating agent will retard PCE degradation. In addition, investigations using free radical probe compounds and radical scavengers revealed that PCE was primarily degraded by HO• radical oxidation in both the chelated and non-chelated systems, while O2•− also participated in the non-chelated system and the OA and Glu modified systems. According to the electron paramagnetic resonance (EPR) studies, the presence of HO• in the Fe(III)/SPC system was maintained much longer than that in the Fe(II)/SPC system. The results indicated that the addition of CIT, OA or Glu indeed enhanced the generation of HO• in the first 10 min and promoted degradation efficiency by increasing the amount of Fe(III) and maintaining the concentration of HO• radicals in solution. In conclusion, chelated Fe(III)-based catalyzed SPC oxidation is a promising method for the remediation of PCE-contaminated groundwater. PMID:26549979

Diagnostic value of three-dimensional magnetic resonance imaging of inner ear after intratympanic gadolinium injection, and clinical application of magnetic resonance imaging scoring system in patients with delayed endolymphatic hydrops.

PubMed

Gu, X; Fang, Z-M; Liu, Y; Lin, S-L; Han, B; Zhang, R; Chen, X

2014-01-01

Three-dimensional fluid-attenuated inversion recovery magnetic resonance imaging of the inner ear after intratympanic injection of gadolinium, together with magnetic resonance imaging scoring of the perilymphatic space, were used to investigate the positive identification rate of hydrops and determine the technique's diagnostic value for delayed endolymphatic hydrops. Twenty-five patients with delayed endolymphatic hydrops underwent pure tone audiometry, bithermal caloric testing, vestibular-evoked myogenic potential testing and three-dimensional magnetic resonance imaging of the inner ear after bilateral intratympanic injection of gadolinium. The perilymphatic space of the scanned images was analysed to investigate the positive identification rate of endolymphatic hydrops. According to the magnetic resonance imaging scoring of the perilymphatic space and the diagnostic standard, 84 per cent of the patients examined had endolymphatic hydrops. In comparison, the positive identification rates for vestibular-evoked myogenic potential and bithermal caloric testing were 52 per cent and 72 per cent respectively. Three-dimensional magnetic resonance imaging after intratympanic injection of gadolinium is valuable in the diagnosis of delayed endolymphatic hydrops and its classification. The perilymphatic space scoring system improved the diagnostic accuracy of magnetic resonance imaging.

Gadolinium-enhanced inner ear magnetic resonance imaging for evaluation of delayed endolymphatic hydrops, including a bilateral case.

PubMed

Fukushima, Munehisa; Oya, Ryohei; Akazawa, Hitoshi; Tsuruta, Yukinori; Inohara, Hidenori

2016-01-01

The data suggests that gadolinium-enhanced inner ear MR imaging is useful for diagnosis of delayed endolymphatic hydrops (DEH) because it is independent of inner ear function, and the size of the affected endolymphatic space is clearly enlarged. This study was performed to semi-quantitatively evaluate the endolymphatic space in patients with all types of DEH using gadolinium-enhanced inner ear magnetic resonance (MR) imaging. Seven patients (age range = 21-77 years; five female, two male) with ipsilateral DEH (n = 5), contralateral DEH (n = 1), and bilateral DEH (n = 1). All patients underwent 3T MR imaging 4 h after intravenous injection of gadolinium. Software was used to determine the size of the endolymphatic space. Pure tone audiometry and caloric testing using an electronystagmogram were carried out. One side of the endolymphatic space was dominantly extended in patients with ipsilateral DEH, and both sides of the space were extended in patients with contralateral and bilateral DEH. In patients with ipsilateral DEH, the volume ratio of endolymph to vestibule was 2.5-4.3-times that in the unaffected ear. The volume ratio of endolymph to vestibule was nearly equal in patients with contralateral and bilateral DEH.

Characteristics of Gadolinium Oxide Nanoparticles Using Terahertz Spectroscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Dongkyu; Maeng, Inhee; Son, Joo-Hiuk

2009-04-19

The penetration property of the terahertz electromagnetic (THz) wave is relevant to its use. We used the THz wave spectroscopy system which easily penetrates some materials that do not contain water, e.g., plastic and ceramics. The system has been developed for several purposes, including measuring the properties of semiconductors and bio-materials, and detecting plastic bombs and ceramic knives at airports. It is also used for medical imaging systems, such as magnetic resonance imaging (MRI), at some research institutes. It can show not only the difference in amplitude, but also the difference of the phase of each point of sample. MRImore » technology usually uses contrast agents to enhance the quality of the image. Gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA), made with a heavy metal ion, is commonly used as a clinical MRI contrast agent. Gadolinium oxide (Gd{sub 2}O{sub 3}) nanoparticle is a new contrast agent. It serves to equip the core of each particle with antibodies or ligands. It can freely circulate in blood vessels without amassing in the liver or lungs. This study shows the characteristics of gadolinium oxide nanoparticles to further advance terahertz medical imaging.« less

Gadolinium based contrast agents in current practice: Risks of accumulation and toxicity in patients with normal renal function

PubMed Central

Ranga, Anju; Agarwal, Yatish; Garg, Kanika J

2017-01-01

Despite being decked as the most prized compounds in the nugget box of contrast agents for clinical radiologists, and carrying an indisputable tag of safety of the US Food and Drug Administration for close to three decades, all may not be seemingly well with the family of gadolinium compounds. If the first signs of violations of primum non nocere in relation to gadolinium-based contrast agents (GBCAs) appeared in the millennium year with the first published report of skin fibrosis in patients with compromised renal function, the causal relationship between the development of nephrogenic systemic fibrosis (NSF) and GBCAs, first proposed by two European groups in 2006, further precluded their use in renocompromised patients. The toxicity, pharmacokinetics, and pharmacodynamics of GBCAs, however, has come under hawk-eyed scrutiny with recent reports that gadolinium tends to deposit cumulatively in the brain of patients with normal hepatobiliary function and intact blood–brain barrier. While the jury on the long-term hazard significance of this critical scientific finding is still out, the use of GBCAs must be guided by due clinical diligence, avoidance of repeated doses, and preferring GBCAs with the best safety profiles. PMID:28744073

Gadolinium enhanced cardiovascular magnetic resonance in Anderson-Fabry disease. Evidence for a disease specific abnormality of the myocardial interstitium.

PubMed

Moon, James C C; Sachdev, Bhavesh; Elkington, Andrew G; McKenna, William J; Mehta, Atul; Pennell, Dudley J; Leed, Philip J; Elliott, Perry M

2003-12-01

Anderson-Fabry Disease (AFD), an X-linked disorder of sphingolipid metabolism, is a cause of idiopathic left ventricular hypertrophy but the mechanism of hypertrophy is poorly understood. Gadolinium enhanced cardiovascular magnetic resonance can detect focal myocardial fibrosis. We hypothesised that hyperenhancement would be present in AFD. Eighteen males (mean 43+/-14 years) and eight female heterozygotes (mean 48+/-12 years) with AFD underwent cine and late gadolinium cardiovascular magnetic resonance. Nine male (50%) had myocardial hyperenhancement ranging from 3.4% to 20.6% (mean 7.7+/-5.7%) of total myocardium; in males, percentage hyperenhancement related to LV mass index (r=0.78, P=0.0002) but not to ejection fraction or left ventricular volumes. Lesser hyperenhancement was also found in four (50%) heterozygous females (mean 4.6%). In 12 (92%) patients with abnormal gadolinium uptake, hyperenhancement occurred in the basal infero-lateral wall where, unlike myocardial infarction, it was not sub-endocardial. In two male patients with severe LVH (left ventricular hypertrophy) and systolic impairment there was additional hyperenhancement in other myocardial segments. These observations suggests that myocardial fibrosis occurs in AFD and may contribute to the hypertrophy and the natural history of the disease.

Application of an oscillation-type linear cadmium telluride detector to enhanced gadolinium K-edge computed tomography

NASA Astrophysics Data System (ADS)

Matsukiyo, Hiroshi; Sato, Eiichi; Hagiwara, Osahiko; Abudurexiti, Abulajiang; Osawa, Akihiro; Enomoto, Toshiyuki; Watanabe, Manabu; Nagao, Jiro; Sato, Shigehiro; Ogawa, Akira; Onagawa, Jun

2011-03-01

A linear cadmium telluride (CdTe) detector is useful for carrying out energy-discrimination X-ray imaging, including computed tomography (CT). To perform enhanced gadolinium K-edge CT, we used an oscillation-type linear CdTe detector with an energy resolution of 1.2 keV. CT is performed by repeating the linear scan and the rotation of an object. Penetrating X-ray photons from the object are detected by the CdTe detector, and event signals of X-ray photons are produced using charge-sensitive and shaping amplifiers. Both the photon energy and the energy width are selected using a multichannel analyzer, and the number of photons is counted by a counter card. In energy-discrimination CT, tube voltage and current were 80 kV and 20 μA, respectively, and X-ray intensity was 1.55 μGy/s at 1.0 m from the source at a tube voltage of 80 kV. Demonstration of enhanced gadolinium K-edge X-ray CT was carried out by selecting photons with energies just beyond gadolinium K-edge energy of 50.3 keV.

Investigation of suspected Guillain-Barre syndrome in childhood: what is the role for gadolinium enhanced magnetic resonance imaging of the spine?

PubMed

Smith, Nicholas; Pereira, John; Grattan-Smith, Padraic

2014-10-01

To review the role of gadolinium-enhanced magnetic resonance imaging of the spine in the diagnosis of paediatric Guillain-Barre syndrome and compare it with nerve conduction studies and cerebrospinal fluid analysis. A retrospective review of investigations undertaken in children admitted to our institution with acute Guillain-Barre syndrome over a 10-year period was performed. Seven of eight children (88%) displayed post-gadolinium nerve root enhancement consistent with Guillain-Barre syndrome. This compared with supportive nerve conduction studies in 21/24 children (88%) and cerebrospinal fluid protein analysis consistent with the diagnosis in 16/20 children (80%). Nerve conduction studies are the recognised 'gold standard' technique for confirming a clinical diagnosis of Guillain-Barre syndrome. In this study, a high positive rate was demonstrated. While more experience is necessary, this study and the literature support gadolinium enhanced magnetic resonance imaging of the spine as a valuable, although not necessarily superior, investigation in the diagnosis of Guillain-Barre syndrome. It may be of particular benefit when specialist neurophysiology expertise is unavailable. © 2010 The Authors. Journal compilation © 2010 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

Timed non-transferrin bound iron determinations probe the origin of chelatable iron pools during deferiprone regimens and predict chelation response

PubMed Central

Aydinok, Yesim; Evans, Patricia; Manz, Chantal Y.; Porter, John B.

2012-01-01

Background Plasma non-transferrin bound iron refers to heterogeneous plasma iron species, not bound to transferrin, which appear in conditions of iron overload and ineffective erythropoiesis. The clinical utility of non-transferrin bound iron in predicting complications from iron overload, or response to chelation therapy remains unproven. We undertook carefully timed measurements of non-transferrin bound iron to explore the origin of chelatable iron and to predict clinical response to deferiprone. Design and Methods Non-transferrin bound iron levels were determined at baseline and after 1 week of chelation in 32 patients with thalassemia major receiving deferiprone alone, desferrioxamine alone, or a combination of the two chelators. Samples were taken at baseline, following a 2-week washout without chelation, and after 1 week of chelation, this last sample being taken 10 hours after the previous evening dose of deferiprone and, in those receiving desferrioxamine, 24 hours after cessation of the overnight subcutaneous infusion. Absolute or relative non-transferrin bound iron levels were related to transfusional iron loading rates, liver iron concentration, 24-hour urine iron and response to chelation therapy over the subsequent year. Results Changes in non-transferrin bound iron at week 1 were correlated positively with baseline liver iron, and inversely with transfusional iron loading rates, with deferiprone-containing regimens but not with desferrioxamine monotherapy. Changes in week 1 non-transferrin bound iron were also directly proportional to the plasma concentration of deferiprone-iron complexes and correlated significantly with urine iron excretion and with changes in liver iron concentration over the next 12 months. Conclusions The widely used assay chosen for this study detects both endogenous non-transferrin bound iron and the iron complexes of deferiprone. The week 1 increments reflect chelatable iron derived both from liver stores and from red cell catabolism. These increments correlate with urinary iron excretion and the change in liver iron concentration over the subsequent year thus predicting response to deferiprone-containing chelation regimes. This clinical study was registered at clinical.trials.gov with the number NCT00350662. PMID:22180427

Colour and stability assessment of blue ferric anthocyanin chelates in liquid pectin-stabilised model systems.

PubMed

Buchweitz, M; Brauch, J; Carle, R; Kammerer, D R

2013-06-01

The formation of blue coloured ferric anthocyanin chelates and their colour stability during storage and thermal treatment were monitored in a pH range relevant to food (3.6-5.0). Liquid model systems were composed of different types of Citrus pectins, juices (J) and the respective phenolic extracts (E) from elderberry (EB), black currant (BC), red cabbage (RC) and purple carrot (PC) in the presence of ferric ions. For EB, BC and PC, pure blue colours devoid of a violet tint were exclusively observed for the phenolic extracts and at pH values ≥ 4.5 in model systems containing high methoxylated and amidated pectins, respectively. Colour and its stability strongly depended on the amount of ferric ions and the plant source; however, colour decay could generally be described as a pseudo-first-order kinetics. Despite optimal colour hues for RC-E and RC-J, storage and heat stabilities were poor. Highest colour intensities and best stabilities were observed for model systems containing PC-E at a molar anthocyanin:ferric ion ratio of 1:2. Ascorbic and lactic acids interfered with ferric ions, thus significantly affecting blue colour evolution and stability. Colour loss strongly depended on heat exposure with activation energies ranging between 60.5 and 78.4 kJ/mol. The comprehensive evaluation of the interrelationship of pigment source, pH conditions and pectin type on chelate formation and stability demonstrated that ferric anthocyanin chelates are promising natural blue food colourants. Copyright © 2012 Elsevier Ltd. All rights reserved.

Clinical efficacy and safety of chelation treatment with typical penicillamine in cross combination with DMPS repeatedly for Wilson's disease.

PubMed

Xu, San-Qing; Li, Xu-Fang; Zhu, Hui-Yun; Liu, Yan; Fang, Feng; Chen, Ling

2013-10-01

The aim of this study was to assess the clinical efficacy and safety of chelation treatment with penicillamine (PCA) in cross combination with sodium 2, 3-dimercapto-1-propane sulfonate (DMPS) repeatedly in patients with Wilson's disease (WD). Thirty-five patients with WD were enrolled. They were administrated intravenous DMPS in cross combination with oral PCA alternately which was practiced repeatedly, all with Zinc in the meantime. During the treatment, clinical observations and 24-h urine copper excretion as well as adverse effects of medicines were recorded and analyzed. Although the incidence of adverse effects was not significantly different after either intravenous DMPS or oral PCA treatment, levels of 24-h urine copper tended to be higher after short-term intravenous DMPS than that of oral PCA. Adverse effects in the course of intravenous DMPS were mainly neutropenia, thrombocytopenia, allergic reaction and bleeding tendency. As compared with oral PCA alone or intravenous DMPS alone, such repeated cross combination treatment could as much as possible avoid continued drug adverse effects or poor curative effect and had less chance to stop treatment in WD patients. Improved or recovered liver function in 71% of the patients, alleviated neurologic symptoms in 50% of the patients, and disappeared hematuria in 70% of the patients could be observed during the follow-up period of 6 months to 5 years after such combined chelation regimen. Chelation treatment repeatedly with oral penicillamine in cross combination with intravenous DMPS alternately could be more beneficial for WD patients to relieve symptoms, avoid continued drug adverse effects and maintain lifelong therapy.

Polyaminoquinoline iron chelators for vectorization of antiproliferative agents: design, synthesis, and validation.

PubMed

Corcé, Vincent; Morin, Emmanuelle; Guihéneuf, Solène; Renault, Eric; Renaud, Stéphanie; Cannie, Isabelle; Tripier, Raphaël; Lima, Luís M P; Julienne, Karine; Gouin, Sébastien G; Loréal, Olivier; Deniaud, David; Gaboriau, François

2012-09-19

Iron chelation in tumoral cells has been reported as potentially useful during antitumoral treatment. Our aim was to develop new polyaminoquinoline iron chelators targeting tumoral cells. For this purpose, we designed, synthesized, and evaluated the biological activity of a new generation of iron chelators, which we named Quilamines, based on an 8-hydroxyquinoline (8-HQ) scaffold linked to linear polyamine vectors. These were designed to target tumor cells expressing an overactive polyamine transport system (PTS). A set of Quilamines bearing variable polyamine chains was designed and assessed for their ability to interact with iron. Quilamines were also screened for their cytostatic/cytotoxic effects and their selective uptake by the PTS in the CHO cell line. Our results show that both the 8-HQ moiety and the polyamine part participate in the iron coordination. HQ1-44, the most promising Quilamine identified, presents a homospermidine moiety and was shown to be highly taken up by the PTS and to display an efficient antiproliferative activity that occurred in the micromolar range. In addition, cytotoxicity was only observed at concentrations higher than 100 μM. We also demonstrated the high complexation capacity of HQ1-44 with iron while much weaker complexes were formed with other cations, indicative of a high selectivity. We applied the density functional theory to study the binding energy and the electronic structure of prototypical iron(III)-Quilamine complexes. On the basis of these calculations, Quilamine HQ1-44 is a strong tridentate ligand for iron(III) especially in the form of a 1:2 complex.

Biocompatible Polyhydroxyethylaspartamide-based Micelles with Gadolinium for MRI Contrast Agents

NASA Astrophysics Data System (ADS)

Jeong, Sang Young; Kim, Hyo Jeong; Kwak, Byung-Kook; Lee, Ha-Young; Seong, Hasoo; Shin, Byung Cheol; Yuk, Soon Hong; Hwang, Sung-Joo; Cho, Sun Hang

2010-12-01

Biocompatible poly-[ N-(2-hydroxyethyl)- d, l-aspartamide]-methoxypoly(ethyleneglycol)-hexadecylamine (PHEA-mPEG-C16) conjugated with 1,4,7,10-tetraazacyclododecan-1,4,7,10-tetraacetic acid-gadolinium (DOTA-Gd) via ethylenediamine (ED) was synthesized as a magnetic resonance imaging (MRI) contrast agent. Amphiphilic PHEA-mPEG-C16-ED-DOTA-Gd forms micelle in aqueous solution. All the synthesized materials were characterized by proton nuclear magnetic resonance (1H NMR). Micelle size and shape were examined by dynamic light scattering (DLS) and atomic force microscopy (AFM). Micelles with PHEA-mPEG-C16-ED-DOTA-Gd showed higher relaxivities than the commercially available gadolinium contrast agent. Moreover, the signal intensity of a rabbit liver was effectively increased after intravenous injection of PHEA-mPEG-C16-ED-DOTA-Gd.

Renal function, nephrogenic systemic fibrosis and other adverse reactions associated with gadolinium-based contrast media.

PubMed

Canga, Ana; Kislikova, Maria; Martínez-Gálvez, María; Arias, Mercedes; Fraga-Rivas, Patricia; Poyatos, Cecilio; de Francisco, Angel L M

2014-01-01

Nephrogenic systemic fibrosis is a fibrosing disorder that affects patients with impaired renal function and is associated with the administration of gadolinium-based contrast media used in MRI. Despite being in a group of drugs that were considered safe, report about this potentially serious adverse reaction was a turning point in the administration guidelines of these contrast media. There has been an attempt to establish safety parameters to identify patients with risk factors of renal failure. The close pharmacovigilance and strict observation of current regulations, with special attention being paid to the value of glomerular filtration, have reduced the published cases involving the use of gadolinium-based contrast media. In a meeting between radiologists and nephrologists we reviewed the most relevant aspects currently and recommendations for its prevention.

The performance of hafnium and gadolinium self powered neutron detectors in the TREAT reactor

NASA Astrophysics Data System (ADS)

Imel, G. R.; Hart, P. R.

1996-05-01

The use of gadolinium and hafnium self powered neutron detectors in a transient reactor is described in this paper. The detectors were calibrated to the fission rate of U-235 using calibrated fission chambers; the calibration factors were tested in two reactors in steady state and found to be consistent. Calibration of the detectors in transient reactor conditions was done by using uranium wires that were analyzed by radiochemistry techniques to determine total fissions during the transient. This was correlated to the time-integrated current of the detectors during the transient. A temperature correction factor was derived to account for self-shielding effects in the hafnium and gadolinium detectors. The dynamic response of the detectors under transient conditions was studied, and found to be excellent.

Electron magnetic resonance investigation of gadolinium diffusion in zircon powders

NASA Astrophysics Data System (ADS)

de Biasi, R. S.; Grillo, M. L. N.

2011-11-01

The electron magnetic resonance (EMR) technique was used to investigate the diffusion of gadolinium in zircon (ZrSiO4) powders. The EMR absorption intensity was measured for several annealing times and three different temperatures of isothermal annealing: 1273, 1323 and 1373 K. The activation energy for diffusion, calculated from the experimental data using a theoretical model based on the Fick equation, was found to be EA=506±5 kJ mol-1. This value is close to the ones for the diffusion of Gd in UO2 and CeO2, but much larger than for the diffusion of gadolinium in a compound with the same crystal structure as zircon, YVO4. This is attributed to a difference in the relative sizes of the ions involved in the diffusion process.

Current status of SK-Gd project and EGADS

NASA Astrophysics Data System (ADS)

Xu, Chenyuan; Super-Kamiokande Collaboration

2016-05-01

Supernova Relic Neutrino (SRN) has not been observed yet because of its low event rate and high background. By adding gadolinium into water Cherenkov detector, inverse beta decay will have two signals, the prompt one is positron signal and the delayed one is a ~8 MeV gamma cascade from neutron capture on gadolinium. By this way, background for SRN can be largely reduced by detecting prompt and delayed signals coincidently, and Super-K will also have the ability to distinguish neutrino and anti-neutrino. SK-Gd is a R&D project proposed to dissolve gadolinium into Super-K. As a part of it, EGADS, a 200 ton water Cherenkov detector was built in Kamioka mine. Current status of SK-Gd project and the physics work being performed in EGADS will be presented here.

Graphene oxide-gadolinium (III) oxide nanoparticle composite: a novel MR contrast agent with high longitudinal and transverse relaxivity

NASA Astrophysics Data System (ADS)

Venkatesha, N.; Poojar, Pavan; Geethanath, Sairam; Srivastava, Chandan

2014-12-01

Production of bio-compatible contrast agent materials to enhance the sensitivity of the magnetic resonance imaging (MRI) technique is a highly active area in MRI related research. This work illustrates the potential of a new material: graphene oxide-gadolinium (III) oxide nanoparticle (GO-Gd2O3) composite in yielding both transverse (16.3 mM-1 s-1) and longitudinal relaxivity (40 mM-1 s-1) values which are significantly higher than the proton relaxivity values achieved using the gadolinium based contrast agents currently used in MRI. Such high proton relaxivity values can facilitate low dosage of GO-Gd2O3 composite for obtaining both T1 and T2 weighted high signal-to-noise ratio images in MRI.

Suppression of Rabbit VX‐2 Subcutaneous Tumor Growth by Gadolinium Neutron Capture Therapy

PubMed Central

Tokita, Nobuhiko; Tokuuye, Koichi; Satoh, Michinao; Churei, Hisahiko; Pechoux, Cécile Le; Kobayashi, Tooru; Kanda, Keiji

1993-01-01

VX‐2 tumors growing in hind legs of New Zealand White rabbits (n=4) were exposed to thermal neutrons for 40 min (2.1 × 1012 neutrons cm−2) while one of two hind leg tumors of each rabbit was infused continuously with meglumine gadopentetate through a branch of the left femoral artery. The contralateral (uninfused) tumors served as controls. Although no differential distribution of gadolinium was achieved between the tumor and its adjacent normal tissue, the gadolinium concentration in the infused tumor was approximately 5–6 fold higher than that in the contralateral tumor. Growth of gadolinium‐infused tumors was significantly inhibited compared to that of control tumors (P<0.05) between the 16th and 23rd days after treatment. PMID:8407547

Gadolinium concentration analysis in brain phantom by X-ray fluorescence.

PubMed

Almalki, Musaed; Majid, Samir Abdul; Butler, Philip H; Reinisch, Lou

2010-06-01

We have measured the X-ray fluorescence from gadolinium as a function of concentration and position in tumors of different sizes and shapes in a head phantom. The gadolinium fluorescence was excited with a 36 GBq Am-241 source. The fluorescence signal was detected with a CdTe detector and a multi-channel analyzer. The fluorescence peak was clearly separated from the scattered X-rays. Concentrations of 5.62-78.63 mg/ml of Gd ion were used in 1, 2, and 3 cm diameter spherical tumors and a 2x4 cm oblate spheroid tumor. The data show trends approaching saturation for the highest concentrations, probably due to reabsorption in the tumor. A comparison of X-ray photographic imaging and densitometer measurements to determine concentration is also presented.

Dramatic impact of the giant local magnetic fields on spin-dependent recombination processes in gadolinium based garnets

DOE Office of Scientific and Technical Information (OSTI.GOV)

Romanov, N. G., E-mail: nikolai.romanov@mail.ioffe.ru; Tolmachev, D. O.; Gurin, A. S.

2015-06-29

A giant magnetic field effect on spin-dependent recombination of the radiation-induced defects has been found in cerium doped gadolinium based garnet crystals and ceramics, promising materials for scintillator applications. A sharp and strong increase in the afterglow intensity stimulated by external magnetic field and an evidence of the magnetic field memory have been discovered. The effect was ascribed to huge Gd-induced internal magnetic fields, which suppress the recombination, and cross-relaxation with Gd{sup 3+} ions leading to reorientation of the spins of the electron and hole centers. Thus, the spin system of radiation-induced defects in gadolinium garnet based scintillator materials wasmore » shown to accumulate significant energy which can be released in external magnetic fields.« less

Tissue gadolinium deposition in renally impaired rats exposed to different gadolinium-based MRI contrast agents: evaluation with inductively coupled plasma mass spectrometry (ICP-MS).

PubMed

Sato, Tomohiro; Ito, Katsuyoshi; Tamada, Tsutomu; Kanki, Akihiko; Watanabe, Shigeru; Nishimura, Hirotake; Tanimoto, Daigo; Higashi, Hiroki; Yamamoto, Akira

2013-10-01

To quantify tissue gadolinium (Gd) deposition in renally impaired rats exposed to Gd-EOB-DTPA and other Gd-based MRI contrast agents by means of inductively coupled plasma mass spectrometry (ICP-MS), and to compare the differences in distribution among major organs as possible triggers for nephrogenic systemic fibrosis (NSF). A total of 15 renally impaired rats were injected with Gd-EOB-DTPA, Gd-DTPA-BMA and Gd-HP-DO3A. Gd contents of skin, liver, kidney, lung, heart, spleen, diaphragm and femoral muscle were measured by inductively coupled plasma mass spectrometry (ICP-MS). Histological assessment was also conducted. Tissue Gd deposition in all organs was significantly higher (P=0.005~0.009) in the Gd-DTPA-BMA group than in the Gd-HP-DO3A and Gd-EOB-DTPA groups. In the Gd-DTPA-BMA group, Gd was predominantly deposited in kidney (1306±605.7μg/g), followed by skin, liver, lung, spleen, femoral muscle, diaphragm and heart. Comparing Gd-HP-DO3A and Gd-EOB-DTPA groups, Gd depositions in the kidney, liver and lung were significantly lower (P=0.009~0.011) in the Gd-EOB-DTPA group than in the Gd-HP-DO3A group although no significant differences were seen for any other organs. Gd-EOB-DTPA is a stable and safe Gd-based contrast agent (GBCA) showing lower Gd deposition in major organs in renally impaired rats, compared with other GBCAs. This fact suggests that the risk of NSF onset would be low in the use of Gd-EOB-DTPA. Copyright © 2013 Elsevier Inc. All rights reserved.

Intraoperative Near-Infrared Optical Imaging Can Localize Gadolinium-Enhancing Gliomas During Surgery

PubMed Central

Lee, John Y-K.; Thawani, Jayesh P.; Pierce, John; Zeh, Ryan; Martinez-Lage, Maria; Chanin, Michelle; Venegas, Ollin; Nims, Sarah; Learned, Kim; Keating, Jane; Singhal, Sunil

2016-01-01

Background Although real-time localization of gliomas has improved with intraoperative image guidance systems, these tools are limited by brain shift, surgical cavity deformation, and expense. Objective To propose a novel method to perform near-infrared (NIR) imaging during glioma resections based on preclinical and clinical investigations, in order to localize tumors and to potentially identify residual disease. Methods Fifteen patients were identified and administered an FDA-approved, NIR contrast agent (Second Window indocyanine green [ICG], 5 mg/kg) prior to surgical resection. An NIR camera was utilized to localize the tumor prior to resection and to visualize surgical margins following resection. Neuropathology and MR imaging data were used to assess the accuracy and precision of NIR-fluorescence in identifying tumor tissue. Results NIR visualization of 15 gliomas (10 glioblastoma multiforme, 1 anaplastic astrocytoma, 2 low grade astrocytoma, 1 juvenile pilocytic astrocytoma, and 1 ganglioglioma) was performed 22.7 hours (mean) after intravenous injection of ICG. During surgery, 12/15 tumors were visualized with the NIR camera. The mean signal-to-background ratio was 9.5 ± 0.8 and fluorescence was noted through the dura to a maximum parenchymal depth of 13 mm. The best predictor of positive fluorescence was enhancement on T1-weighted imaging; this correlated with SBR (P = .03). Non-enhancing tumors did not demonstrate NIR fluorescence. Using pathology as the gold standard, the technique demonstrated a sensitivity of 98% and specificity of 45% to identify tumor in gadolinium-enhancing specimens (n = 71). Conclusion Using Second Window ICG, gadolinium-enhancing tumors can be localized through brain parenchyma intraoperatively. Its utility for margin detection is promising but limited by lower specificity. PMID:27741220

Gadolinium and ruthenium red attenuate remote hind limb preconditioning-induced cardioprotection: possible role of TRP and especially TRPV channels.

PubMed

Randhawa, Puneet Kaur; Jaggi, Amteshwar Singh

2016-08-01

Remote ischemic preconditioning is a well reported therapeutic strategy that induces cardioprotective effects but the underlying intracellular mechanisms have not been widely explored. The current study was designed to investigate the involvement of TRP and especially TRPV channels in remote hind limb preconditioning-induced cardioprotection. Remote hind limb preconditioning stimulus (4 alternate cycles of inflation and deflation of 5 min each) was delivered using a blood pressure cuff tied on the hind limb of the anesthetized rat. Using Langendorff's system, the heart was perfused and subjected to 30-min ischemia and 120-min reperfusion. The myocardial injury was assessed by measuring infarct size, lactate dehydrogenase (LDH), creatine kinase (CK), LVDP, +dp/dtmax, -dp/dtmin, heart rate, and coronary flow rate. Gadolinium, TRP blocker, and ruthenium red, TRPV channel blocker, were employed as pharmacological tools. Remote hind limb preconditioning significantly reduced the infarct size, LDH release, CK release and improved coronary flow rate, hemodynamic parameters including LVDP, +dp/dtmax, -dp/dtmin, and heart rate. However, gadolinium (7.5 and 15 mg kg(-1)) and ruthenium red (4 and 8 mg kg(-1)) significantly attenuated the cardioprotective effects suggesting the involvement of TRP especially TRPV channels in mediating remote hind limb preconditioning-induced cardioprotection. Remote hind limb preconditioning stimulus possibly activates TRPV channels on the heart or sensory nerve fibers innervating the heart to induce cardioprotective effects. Alternatively, remote hind limb preconditioning stimulus may also activate the mechanosensitive TRP and especially TRPV channels on the sensory nerve fibers innervating the skeletal muscles to trigger cardioprotective neurogenic signaling cascade. The cardioprotective effects of remote hind limb preconditioning may be mediated via activation of mechanosensitive TRP and especially TRPV channels.

Metal specificity of an iron-responsive element in Alzheimer's APP mRNA 5'untranslated region, tolerance of SH-SY5Y and H4 neural cells to desferrioxamine, clioquinol, VK-28, and a piperazine chelator.

PubMed

Bandyopadhyay, S; Huang, X; Cho, H; Greig, N H; Youdim, M B; Rogers, J T

2006-01-01

Iron closely regulates the expression of the Alzheimer's Amyloid Precursor Protein (APP) gene at the level of message translation by a pathway similar to iron control of the translation of the ferritin L- and H mRNAs by Iron-responsive Elements in their 5' untranslated regions (5'UTRs). Using transfection based assays in SH-SY5Y neuroblastoma cells we tested the relative efficiency by which iron, copper and zinc up-regulate IRE activity in the APP 5'UTR. Desferrioxamine (high affinity Fe3+ chelator), (ii) clioquinol (low affinity Fe/Cu/Zn chelator), (iii) piperazine-1 (oral Fe chelator), (iv) VK-28 (oral Fe chelator), were tested for their relative modulation of APP 5' UTR directed translation of a luciferase reporter gene. Iron chelation based therapeutic strategies for slowing the progression of Alzheimer's disease (and other neurological disorders that manifest iron imbalance) are discussed with regard to the relative neural toxic action of each chelator in SH-SY5Y cells and in H4 glioblastoma cells.

Extraction of metals using supercritical fluid and chelate forming legand

DOEpatents

Wai, Chien M.; Laintz, Kenneth E.

1998-01-01

A method of extracting metalloid and metal species from a solid or liquid material by exposing the material to a supercritical fluid solvent containing a chelating agent is described. The chelating agent forms chelates that are soluble in the supercritical fluid to allow removal of the species from the material. In preferred embodiments, the extraction solvent is supercritical carbon dioxide and the chelating agent is a fluorinated .beta.-diketone. In especially preferred embodiments the extraction solvent is supercritical carbon dioxide, and the chelating agent comprises a fluorinated .beta.-diketone and a trialkyl phosphate, or a fluorinated .beta.-diketone and a trialkylphosphine oxide. Although a trialkyl phosphate can extract lanthanides and actinides from acidic solutions, a binary mixture comprising a fluorinated .beta.-diketone and a trialkyl phosphate or a trialkylphosphine oxide tends to enhance the extraction efficiencies for actinides and lanthanides. The method provides an environmentally benign process for removing contaminants from industrial waste without using acids or biologically harmful solvents. The method is particularly useful for extracting actinides and lanthanides from acidic solutions. The chelate and supercritical fluid can be regenerated, and the contaminant species recovered, to provide an economic, efficient process.

Extraction of metals using supercritical fluid and chelate forming ligand

DOEpatents

Wai, C.M.; Laintz, K.E.

1998-03-24

A method of extracting metalloid and metal species from a solid or liquid material by exposing the material to a supercritical fluid solvent containing a chelating agent is described. The chelating agent forms chelates that are soluble in the supercritical fluid to allow removal of the species from the material. In preferred embodiments, the extraction solvent is supercritical carbon dioxide and the chelating agent is a fluorinated {beta}-diketone. In especially preferred embodiments the extraction solvent is supercritical carbon dioxide, and the chelating agent comprises a fluorinated {beta}-diketone and a trialkyl phosphate, or a fluorinated {beta}-diketone and a trialkylphosphine oxide. Although a trialkyl phosphate can extract lanthanides and actinides from acidic solutions, a binary mixture comprising a fluorinated {beta}-diketone and a trialkyl phosphate or a trialkylphosphine oxide tends to enhance the extraction efficiencies for actinides and lanthanides. The method provides an environmentally benign process for removing contaminants from industrial waste without using acids or biologically harmful solvents. The method is particularly useful for extracting actinides and lanthanides from acidic solutions. The chelate and supercritical fluid can be regenerated, and the contaminant species recovered, to provide an economic, efficient process. 7 figs.

Effect of the tether on the Mg(II), Ca(II), Cu(II) and Fe(III) stability constants and pM values of chelating agents related to EDDHA.

PubMed

Sierra, Miguel A; Gómez-Gallego, Mar; Alcázar, Roberto; Lucena, Juan J; Yunta, Felipe; García-Marco, Sonia

2004-11-07

The effect of the length and the structure of the tether on the chelating ability of EDDHA-like chelates have not been established. In this work, PDDHA (propylenediamine-N,N'-bis(o-hydroxyphenyl)acetic acid), BDDHA (butylenediamine-N,N'-bis(o-hydroxyphenyl)acetic acid) and XDDHA (p-xylylenediamine-N,N'-bis(o-hydroxyphenyl)acetic acid) have been obtained and their chemical behaviour has been studied and compared with that of EDDHA following our methodology. The purity of the chelating agents, and their protonation, Ca(II), Mg(II), Fe(III) and Cu(II) stability constants and pM values have been determined. The stability constants and pM values indicate that EDDHA forms the most stable chelates followed by PDDHA. However, the differences among the pFe values are small when a nutrient solution is used, and in these conditions the XDDHA/Fe(III) chelate is the most stable. The results obtained in this work indicate that all the chelating agents studied can be used as iron chlorosis correctors and they can be applied to soil/plant systems.

Effectiveness of late gadolinium enhancement to improve outcomes prediction in patients referred for cardiovascular magnetic resonance after echocardiography

PubMed Central

2013-01-01

Background Echocardiography (echo) is a first line test to assess cardiac structure and function. It is not known if cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE) ordered during routine clinical practice in selected patients can add additional prognostic information after routine echo. We assessed whether CMR improves outcomes prediction after contemporaneous echo, which may have implications for efforts to optimize processes of care, assess effectiveness, and allocate limited health care resources. Methods and results We prospectively enrolled 1044 consecutive patients referred for CMR. There were 38 deaths and 3 cardiac transplants over a median follow-up of 1.0 years (IQR 0.4-1.5). We first reproduced previous survival curve strata (presence of LGE and ejection fraction (EF) < 50%) for transplant free survival, to support generalizability of any findings. Then, in a subset (n = 444) with contemporaneous echo (median 3 days apart, IQR 1–9), EF by echo (assessed visually) or CMR were modestly correlated (R2 = 0.66, p < 0.001), and 30 deaths and 3 transplants occurred over a median follow-up of 0.83 years (IQR 0.29-1.40). CMR EF predicted mortality better than echo EF in univariable Cox models (Integrated Discrimination Improvement (IDI) 0.018, 95% CI 0.008-0.034; Net Reclassification Improvement (NRI) 0.51, 95% CI 0.11-0.85). Finally, LGE further improved prediction beyond EF as determined by hazard ratios, NRI, and IDI in all Cox models predicting mortality or transplant free survival, adjusting for age, gender, wall motion, and EF. Conclusions Among those referred for CMR after echocardiography, CMR with LGE further improves risk stratification of individuals at risk for death or death/cardiac transplant. PMID:23324403

Assessment of late cardiomyopathy by magnetic resonance imaging in patients with acute promyelocytic leukaemia treated with all-trans retinoic acid and idarubicin.

PubMed

Rodríguez-Veiga, Rebeca; Igual, Begoña; Montesinos, Pau; Tormo, Mar; Sayas, Mª José; Linares, Mariano; Fernández, José María; Salvador, Antonio; Maceira-González, Alicia; Estornell, Jordi; Calabuig, Marisa; Pedreño, María; Roig, Mónica; Sanz, Jaime; Sanz, Guillermo; Carretero, Carlos; Boluda, Blanca; Martínez-Cuadrón, David; Sanz, Miguel Ángel

2017-07-01

Late cardiomyopathy CMP is regarded as a potential severe long-term complication after anthracycline-based regimens for acute promyelocitic leukaemia (APL). We assess by MRI the incidence and severity of clinical and subclinical long-term CMP in a cohort of adult APL patients in first complete remission with PETHEMA trials. Adult patients diagnosed with APL in first complete remission lasting ≥2 years underwent anamnesis and physical examination and were asked to perform a cardiac MRI. Clinical CMP was defined as radiographic and physical signs of heart failure accompanied by symptoms or by left ventricle ejection fraction (LVEF) <45% by MRI with or without symptoms. Subclinical CMP was defined as the following MRI abnormalities: LVEF 45-50% or late gadolinium enhancement or two or more of LVEF ≤55%, left ventricle end-diastolic volume index ≥98 ml/m 2 , left ventricle end-systolic volume index ≥38 ml/m 2 , right ventricle end-diastolic volume index ≥106 ml/m 2 and regional wall motion abnormalities. Of the 82 patients enrolled in the study, median cumulative dose of anthracyclines (doxorubicin equivalence) was 650 mg/m 2 , and median time from APL diagnosis to the study was 87 months (range, 24-195). Seven out of 57 patients with available MRI (12%) had subclinical CMP (all of them showed late gadolinium enhancement in MRI), and none had clinical CMP. Among the 25 patients without MRI, none had CMP by chest X-ray and physical assessment. In summary, we found 12% of subclinical and no clinical late CMP assessed by MRI in APL patients treated with PETHEMA protocols. Due to the low number of patients, we must interpret our results cautiously.

Relationship among chelator adherence, change in chelators, and quality of life in thalassemia.

PubMed

Trachtenberg, Felicia L; Gerstenberger, Eric; Xu, Yan; Mednick, Lauren; Sobota, Amy; Ware, Hannah; Thompson, Alexis A; Neufeld, Ellis J; Yamashita, Robert

2014-10-01

Thalassemia, a chronic blood disease, necessitates life-long adherence to blood transfusions and chelation therapy to reduce iron overload. We examine stability of health-related quality of life (HRQOL) in thalassemia and adherence to chelation therapy over time, especially after changes in chelator choice. Thalassemia Longitudinal Cohort participants in the USA, UK, and Canada completed the SF-36v2 (ages 14+) and the PF-28 CHQ (parents of children <14 years). Chelation adherence was defined as self-reported percent of doses administered in the last 4 weeks. Two hundred and fifty-eight adults/adolescents (mean 29.7 years) and 133 children (mean 8.5 years) completed a mean of 2.8-years follow-up. Children made few chelator changes, whereas a mean of 2.2 changes was observed among the 37% of adults/adolescents who made chelator changes, mainly due to patient preference or medical necessity. Physical HRQOL improved among those with lower iron burden (better health status) at baseline who made a single change in chelator, but declined among participants with multiple changes and/or high iron burden (worse health status). Mental health improved among participants with lower iron burden, but iron overload was negatively associated with social functioning. Adherence did not significantly change over follow-up except for an increase after a change from deferoxamine (DFO) infusion to oral deferasirox (p = 0.03). Predictors of lower adherence for adults/adolescents at follow-up included side effects, smoking, younger age, problems preparing DFO, increased number of days per week DFO prescribed, and lower physical quality of life . Strategies to balance medical needs with family, work, and personal life may assist in adherence.

Phenomenon of hot-cold hemolysis: chelator-induced lysis of sphingomyelinase-treated erythrocytes.

PubMed Central

Smyth, C J; Möllby, R; Wadström, T

1975-01-01

Staphylococcus aureus produces a phospholipase C specific for sphingomyelin (beta-hemolysin). Erythrocytes with approximately 50% sphingomyelin in their membranes, e.g., from sheep, have been shown to have up to 60% of this phospholipid hydrolyzed by this enzyme at 37 C in isotonic buffered saline without hemolysis. Cooling of sphingomyelinase C-treated erythrocytes to 4 C causes complete lysis of the cells, a phenomenon known as hot-cold hemolysis. The addition of ethylenediaminetetraacetate (EDTA) to sheep erythrocytes preincubated with sphingomyelinase C was found to induce rapid hemolysis at 37 C. The treated cells became susceptible to chelator-induced hemolysis and to hot-cold hemolysis simultaneously, and the degree of lysis of both mechanisms increased equally with prolonged preincubation with sphingomyelinase C. Erythrocytes of species not readily susceptible to hot-cold hemolysis were equally insusceptible to chelator-induced lysis. Chelators of the EDTA series were the most effective, whereas chelators more specific for Ca2+, Zn2+, Fe2+, Cu2+, and Mg2+ were without effect. The rate of chelator-induced lysis was dependent on the preincubation period with beta-hemolysin and on the concentration of chelator added. The optimal concentration of EDTA was found to equal the amount of exogenously added Mg2+, a cation necessary for sphingomyelinase C activity. Hypotonicity increased the rate of chelator-induced hemolysis, whereas increasing the osmotic pressure to twice isotonic completely inhibited chelator-induced lysis. The data suggest that exogenously added and/or membrane-bound divalent cations are important for the stability of sphingomyelin-depleted membranes. The phenomenon of hot-cold hemolysis may be a consequence of the temperature dependence of divalent ion stabilization. Images PMID:333

Unexpected effect of dry olive leaf extract on the level of DNA damage in lymphocytes of lead intoxicated workers, before and after CaNa2EDTA chelation therapy.

PubMed

Čabarkapa, Andrea; Dekanski, Dragana; Živković, Lada; Milanović-Čabarkapa, Mirjana; Bajić, Vladan; Topalović, Dijana; Giampieri, Francesca; Gasparrini, Massimiliano; Battino, Maurizio; Spremo-Potparević, Biljana

2017-08-01

The CaNa 2 EDTA chelation therapy is often practiced with antioxidant supplementation. Dry olive leaf extract (DOLE) is natural product with antioxidant and DNA protective properties. The effects of DOLE on the levels of DNA damage were investigated ex vivo in peripheral blood lymphocytes (PBLs) of 19 workers occupationally exposed to lead (Pb), before and after CaNa 2 EDTA chelation therapy. DOLE demonstrated pronounced radical scavenging activity in concentrations ≥1 mg/mL, and showed no genotoxicity per se, in concentrations 0.125-1 mg/mL. The level of DNA damage in PBLs of workers before chelation therapy was elevated (24.21 ± 14.26) compared to controls (6.0 ± 3.37). The incubation of PBLs before chelation therapy with selected concentration of DOLE lead to a severe increase of DNA damage (64.03 ± 20.96), exhibiting prooxidant rather than antioxidant effect. After the five-day CaNa 2 EDTA chelation regimen, DNA damage in PBLs of workers decreased (8.26 ± 4.62) significantly compared to baseline. Treatment of PBLs with DOLE after chelation, again produced high level of damage (41.82 ± 23.17) and the acute prooxidant effects of DOLE remained, but, DNA damage was less severe than before chelation. The DOLE exhibits prooxidant effect in presence of Pb in lymphocytes of exposed workers, and its effect is less pronounced following the removal of Pb after standard chelation therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

Optical response measurements of a new class of upconverting luminescent reporters

NASA Astrophysics Data System (ADS)

Xiao, Xudong; Haushalter, Jeanne P.; Weiss, Michael; Faris, Gregory W.

2004-06-01

We have prepared and characterized several lanthanide ion complexes of multidentate ligands or chelates in an effort to develop new luminescent reporters that will be immune to autofluorescence and photobleaching. Our study has involved the characterization of various chelates of Eu, Er, and Tm with respect to relative luminescent efficiency and excited state lifetimes. Included in the list of chelates studied are TTFA, EDTA, DPA, DOTA and DTPA as well as mixed and double chelates. In addition to determining the relative efficiencies and luminescence lifetimes of the lanthanide chelates, we have explored various excitation mechanisms and determined optimum excitation wavelengths. This paper will address the various hurdles encountered in the development of this new class of reporters.

Reusable chelating resins concentrate metal ions from highly dilute solutions

NASA Technical Reports Server (NTRS)

Bauman, A. J.; Weetal, H. H.; Weliky, N.

1966-01-01

Column chromatographic method uses new metal chelating resins for recovering heavy-metal ions from highly dilute solutions. The absorbed heavy-metal cations may be removed from the chelating resins by acid or base washes. The resins are reusable after the washes are completed.

Oxidation-Induced Degradable Nanogels for Iron Chelation

NASA Astrophysics Data System (ADS)

Liu, Zhi; Wang, Yan; Purro, Max; Xiong, May P.

2016-02-01

Iron overload can increase cellular oxidative stress levels due to formation of reactive oxygen species (ROS); untreated, it can be extremely destructive to organs and fatal to patients. Since elevated oxidative stress levels are inherent to the condition in such patients, oxidation-induced degradable nanogels for iron chelation were rationally designed by simultaneously polymerizing oxidation-sensitive host-guest crosslinkers between β-cyclodextrin (β-CD) and ferrocene (Fc) and iron chelating moieties composed of deferoxamine (DFO) into the final gel scaffold in reverse emulsion reaction chambers. UV-Vis absorption and atomic absorption spectroscopy (AAS) was used to verify iron chelating capability of nanogels. These materials can degrade into smaller chelating fragments at rates proportional to the level of oxidative stress present. Conjugating DFO reduces the cytotoxicity of the chelator in the macrophage cells. Importantly, the nanogel can effectively reduce cellular ferritin expression in iron overloaded cells and regulate intracellular iron levels at the same time, which is important for maintaining a homeostatic level of this critical metal in cells.

3-hydroxy-2(1H)-pyridinone chelating agents

DOEpatents

Raymond, K.N.; Xu, J.

1997-04-29

Disclosed is a series of improved metal chelating agents, which are highly effective upon both injection and oral administration; several of the most effective are of low toxicity. These chelating agents incorporate within their structure 1-hydroxy-2-pyridinone (1,2-HOPO) and 3-hydroxy-2-pyridinone (3,2-HOPO) moieties with a substituted carbamoyl group ortho to the hydroxy or oxo groups of the hydroxypyridinone ring. The electron-withdrawing carbamoyl group increases the acidity of the hydroxypyridinones. In the metal complexes of the chelating agents, the amide protons form very strong hydrogen bonds with its adjacent HOPO oxygen donor, making these complexes very stable at physiological conditions. The terminal N-substituents provides a certain degree of lipophilicity to the 3,2-HOPO, increasing oral activity. Also disclosed is a method of making the chelating agents and a method of producing a known compound, 3-hydroxy-1-alkyl-2(1H)pyridinone, used as a precursor to the chelating agent, safely and in large quantities. 2 figs.

3-hydroxy-2(1H)-pyridinone chelating agents

DOEpatents

Raymond, Kenneth N.; Xu, Jide

1997-01-01

Disclosed is a series of improved metal chelating agents, which are highly effective upon both injection and oral administration; several of the most effective are of low toxicity. These chelating agents incorporate within their structure 1-hydroxy-2-pyridinone (1,2-HOPO) and 3-hydroxy-2-pyridinone (3,2-HOPO) moieties with a substituted carbamoyl group ortho to the hydroxy or oxo groups of the hydroxypyridinone ring. The electron-withdrawing carbamoyl group increases the acidity of the hydroxypyridinones. In the metal complexes of said chelating agents, the amide protons form very strong hydrogen bonds with its adjacent HOPO oxygen donor, making these complexes very stable at physiological conditions. The terminal N-substituents provides a certain degree of lipophilicity to said 3,2-HOPO, increasing oral activity. Also disclosed is a method of making the chelating agents and a method of producing a known compound, 3-hydroxy-1-alkyl-2(1H)pyridinone, used as a precursor to the chelating agent, safely and in large quantities.

Synthesis and characterization of dihexyldithiocarbamate as a chelating agent in extraction of gold(III)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fatimah, Soja Siti, E-mail: soja-sf@upi.edu; Department of Chemistry, Faculty of Mathematics and Natural Sciences, Padjadjaran University, Jl. Raya Bandung-Sumedang, Km. 21, Jatinangor; Bahti, Husein H.

2016-02-08

The use of dialkyldithiocarbamates as chelating agents of transition metals have been developing for decades. Many chelating agents have been synthesized and used in the extraction of the metals. Studies on particular aspects of extraction of the metals, such as the effect of increasing hydrophobicity of chelating agents on the effectiveness of the extraction, have been done. However, despite the many studies on the synthesis and applications of this type of chelating agents, interests in the aspect of molecular structure of the synthesized ligands and of their complexes, have been limited. This study aimed at synthesizing and characterizing dihexylthiocarbamate, andmore » using the ligand for the extraction of gold III). Characterization of the ligand and of its metal complex were done by using elemental analysis, DTG, and spectroscopic methods to include NMR, ({sup 1}H, and {sup 13}C), FTIR, and MS-ESI. Data on the synthesis, characterization, and the application of the ligand as a chelating agent are presented.« less

Synthesis and characterization of dihexyldithiocarbamate as a chelating agent in extraction of gold(III)

NASA Astrophysics Data System (ADS)

Fatimah, Soja Siti; Bahti, Husein H.; Hastiawan, Iwan; Permanasari, Anna

2016-02-01

The use of dialkyldithiocarbamates as chelating agents of transition metals have been developing for decades. Many chelating agents have been synthesized and used in the extraction of the metals. Studies on particular aspects of extraction of the metals, such as the effect of increasing hydrophobicity of chelating agents on the effectiveness of the extraction, have been done. However, despite the many studies on the synthesis and applications of this type of chelating agents, interests in the aspect of molecular structure of the synthesized ligands and of their complexes, have been limited. This study aimed at synthesizing and characterizing dihexylthiocarbamate, and using the ligand for the extraction of gold III). Characterization of the ligand and of its metal complex were done by using elemental analysis, DTG, and spectroscopic methods to include NMR, (1H, and 13C), FTIR, and MS-ESI. Data on the synthesis, characterization, and the application of the ligand as a chelating agent are presented.

Oxidation-Induced Degradable Nanogels for Iron Chelation

PubMed Central

Liu, Zhi; Wang, Yan; Purro, Max; Xiong, May P.

2016-01-01

Iron overload can increase cellular oxidative stress levels due to formation of reactive oxygen species (ROS); untreated, it can be extremely destructive to organs and fatal to patients. Since elevated oxidative stress levels are inherent to the condition in such patients, oxidation-induced degradable nanogels for iron chelation were rationally designed by simultaneously polymerizing oxidation-sensitive host-guest crosslinkers between β-cyclodextrin (β-CD) and ferrocene (Fc) and iron chelating moieties composed of deferoxamine (DFO) into the final gel scaffold in reverse emulsion reaction chambers. UV-Vis absorption and atomic absorption spectroscopy (AAS) was used to verify iron chelating capability of nanogels. These materials can degrade into smaller chelating fragments at rates proportional to the level of oxidative stress present. Conjugating DFO reduces the cytotoxicity of the chelator in the macrophage cells. Importantly, the nanogel can effectively reduce cellular ferritin expression in iron overloaded cells and regulate intracellular iron levels at the same time, which is important for maintaining a homeostatic level of this critical metal in cells. PMID:26868174

Switching of the polarization of ferroelectric-ferroelastic gadolinium molybdate in a magnetic field

NASA Astrophysics Data System (ADS)

Yakushkin, E. D.

2017-10-01

A change in the character of the electric switching of polydomain ferroelectric-ferroelastic gadolinium molybdate in an external magnetic field has been detected. This change has been attributed to a magnetically stimulated increase in the pinning of domain walls. Under certain conditions, the loop of switchable polarization is degenerated into an ellipse characteristic of a linear insulator with leakage current.

Fuel bundle design for enhanced usage of plutonium fuel

DOEpatents

Reese, Anthony P.; Stachowski, Russell E.

1995-01-01

A nuclear fuel bundle includes a square array of fuel rods each having a concentration of enriched uranium and plutonium. Each rod of an interior array of the rods also has a concentration of gadolinium. The interior array of rods is surrounded by an exterior array of rods void of gadolinium. By this design, usage of plutonium in the nuclear reactor is enhanced.