23911-26-4Relevant articles and documents
Synthesis and study on magnetic resonance imaging performance of Gd(III)-DTPA-bisfuran-2-carbohydrazide as a potential MRI contrast agent
Wan, Fuxian,Zhang, Tiankai,Li, Changcheng,Jiang, Lin
, p. 288 - 293 (2017)
One novel ligand, diethylenetriamine-N, N?-bi(acetyl-furan-2-carbohydrazide)-N, N?, N?-triacetic acid (H3L), has been synthesized in high yield by the reaction of bicyclic anhydride of diethylenetraiaminepentaacetic acid (DTPA) with furan-2-carbohydrazide. It has three carboxylic groups, and the corresponding nonion complex of Gd(III)-L holding promise of magnetic resonance imaging (MRI) was obtained by treating these ligand with Gd2O3 in water. The efficacy of the contrast agent was assessed by measuring the longitudinal relaxivity (r1) and T1 weighted magnetic resonance imaging in vitro. The r1 of Gd(III)-DTPA-bisfuran-2- carbohydrazide was up to 5.92 mM-1￠s-1, which was 1.27 times higher than that of the analogous MRI contrast agent Gd(III)-DTPA(4.65 mM-1￠s-1) in clinical application. T1 weighted magnetic resonance imaging in vitro showed that proton signal intensity increased with Gd(III) complex concentration and the imaging effect of Gd(III)-DTPA-bisfuran-2-carbohydrazide was superior to that of Gd(III)-DTPA in the same condition. These results showed that the complex might be considered as a potential MRI contrast agent.
Synthesis and Characterization of Amphiphilic Gd(III) Complexes: Gd-DTPA-BA
Zhao, Zheng,Fang, Hui,Qiao, Weihong
, p. 601 - 607 (2018)
Magnetic resonance imaging (MRI) is widely used to identify different diseases. MRI contrast agents, used to enhance the MRI signal, have been studied extensively for precise diagnosis. Based on the advantages of macromolecular MRI contrast agents of higher contrast imaging ability and a longer cycle time, this article modified the most common micromolecular contrast agent (Gd-diethylene triamine pentaacetic acid [DTPA]). 2 long saturated aliphatic chains were attached to both sides of DTPA. DTPA derivatives with 12, 14, and 16 carbon lengths were synthesized and chelated to Gd3+. 3 amphiphilic MRI contrast agents were obtained and their structures were characterized using mass spectrometry, 1H NMR, and Fourier transform infrared. Furthermore, the surface tension of the compounds was measured, and liposomes were prepared by mixing the synthesized amphiphilic molecules with egg lecithin and cholesterol. The assembly behavior of the liposomes was studied using transmission electron microscopy (TEM), dynamic light scattering (DLS), and zeta potential measurements. TEM showed that the liposomes possessed bilayer vesicle structures. The liposome size distribution determined by DLS was from 10 to 1000 nm, and as the aliphatic chain length increased, the polydispersity index (PDI) and zeta potential increased. No obvious changes in the PDI and zeta potential of the liposomes were observed after 5 days at room temperature, suggesting that they possess good stability.
Design and synthesis of novel adenine fluorescence probe based on Eu(III) complexes with dtpa-bis(guanine) ligand
Tian, Fengyun,Jiang, Xiaoqing,Dou, Xuekai,Wu, Qiong,Wang, Jun,Song, Youtao
, p. 194 - 200 (2017)
A novel adenine (Ad) fluorescence probe (EuIII-dtpa-bis(guanine)) was designed and synthesized by improving experimental method based on the Eu(III) complex and dtpa-bis(guanine) ligand. The dtpa-bis(guanine) ligand was first synthesized by the acylation action between dtpaa and guanine (Gu), and the corresponding Eu(III) complex was successfully prepared through heat-refluxing method with dtpa-bis(guanine) ligand. As a novel fluorescence probe, the EuIII-dtpa-bis(guanine) complex can detect adenine (Ad) with characteristics of strong targeting, high specificity and high recognition ability. The detection mechanism of the adenine (Ad) using this probe in buffer solution was studied by ultraviolet-visible (UV–vis) and fluorescence spectroscopy. When the EuIII-dtpa-bis(guanine) was introduced to the adenine (Ad) solution, the fluorescence emission intensity was significantly enhanced. However, adding other bases such as guanine (Gu), xanthine (Xa), hypoxanthine (Hy) and uric acid (Ur) with similar composition and structure to that of adenine (Ad) to the EuIII-dtpa-bis(guanine) solution, the fluorescence emission intensities are nearly invariable. Meanwhile, the interference of guanine (Gu), xanthine (Xa), hypoxanthine (Hy) and uric acid (Ur) on the detection of the adenine using EuIII-dtpa-bis(guanine) probe was also studied. It was found that presence of these bases does not affect the detection of adenine (Ad). A linear response of fluorescence emission intensities of EuIII-dtpa-bis(guanine) at 570?nm as a function of adenine (Ad) concentration in the range of 0.00–5.00?×?10??5?mol?L??1 was observed. The detection limit is about 4.70?×?10??7?mol?L??1.
Synthesis, biological evaluation and molecular docking studies of high-affinity bone targeting N,N'-Bis (alendronate) diethylenetriamene-N,N'-triacetic acid: A bifunctional bone scintigraphy agent
Chadha, Nidhi,Sinha, Deepa,Tiwari, Anjani K.,Chuttani, Krishna,Mishra, Anil K.
, p. 468 - 476 (2013)
A bisphosphonate derivative DTPA-bis(alendronate) conjugate has been synthesized and evaluated as potential radiopharmaceutical for bone imaging. The compound was synthesized by the covalent coupling of DTPA-bis(anhydride) with alendronate and was char-acterized on the basis of IR, NMR and mass spectroscopy. It was labelled with 99mTc with 96% efficacy and was found stable for about 24 h under physiological conditions. Blood kinetic studies of 99mTc DTPA-bis(alendronate) showed a biexponential pattern as well as quick washout from the blood circulation. The biological t1/2(F) and t1/2(S) were found to be 50 min ± 0.001 and 6 h 30 min ± 0.005, respectively. Imaging and biodistribution studies showed a significant accumulation of 99mTc DTPA-bis(alendronate) conjugate at bone site. Bone-to-muscles ratios were 12.08 ± 0.001 at 1 h, 45.33 ± 0.001 at 4 h and 35.83 ± 0.001 at 24 h after post-injection, respectively. The receptor binding of the 99mTc-DTPA-bis (alendronate) was established on human bone cell line (Soas-2) revealed KD = 0.86 nm. The preliminary result of the 99mTc-DTPA-bis(alendronate) is encouraging to carrying out further in vivo experiment for targeted bone imaging because of good-bone-to-normal-organ contrast. Further docking analysis with molecular targets, farnesyl diphosphate synthase, geranylgeranyl pyrophosphate and osteocalcin revealed the high affinity of -17.419 and thus represents strong potential of bone-imaging agent.
Lanthanide-containing polycations for monitoring polyplex dynamics via lanthanide resonance energy transfer
Kelkar, Sneha S.,Xue, Lian,Turner, S. Richard,Reineke, Theresa M.
, p. 1612 - 1624 (2014)
Theranostic nanomaterials have emerged in the past decade that combine therapeutic delivery and diagnostic imaging into one package. Such materials offer the opportunity to aid diagnosis, track therapeutic biodistribution, and monitor drug release. We have developed a series of nucleic acid delivery polymers containing oligoethylene amines that are able to be protonated at physiological pH (for binding/compacting pDNA) and a lanthanide-chelating domain, which imparts diagnostic functionality. Diamine monomers (containing between 3 and 6 Boc-protected ethyleneamines) were prepared via a multistep procedure involving the selective protection and deprotection of primary and secondary amines. The polymer structures were then synthesized by step-growth polymerization of the oligoethylene diamines with a bisanhydride of diethylenetriamine pentaacetic acid (DTPA-BA), yielding degrees of polymerization between 18 and 24. Chelation of the polymers with gadolinium and terbium was performed to offer MRI contrast agent and luminescence properties, respectively. All of the polymer chelates were found to house approximately one water coordination site, as calculated by the Horrocks equation and possess longitudinal relaxivities (r1, on a per Gd basis) at least twice that of Magnevist, a clinical contrast agent. All the structures formed polyplexes with pDNA with highly positive zeta potentials and hydrodynamic diameters around 50-80 nm. Lanthanide resonance energy transfer (LRET) was used to monitor polyplex association and dissociation. Polyplexes were formed using the donor-acceptor pair comprising of terbium-chelated polymer with five ethyleneamines within the repeat unit (6c-Tb) and tetramethyl rhodamine (TMR)-labeled pDNA. Association/dissociation in the presence of heparin and NaCl was monitored. The effect of amine number along the polymer backbone on transfection efficiency and cytotoxicity was also investigated. None of the polymers revealed cytotoxic effects with cultured cells; however, the polymer with six ethyleneamines clearly offered the highest transfection efficiency. This preliminary study offers insight into the development of materials with the ability to monitor polyplex unpackaging over time within the cellular environment.
Design and preparation of gadolinium-reservoir microcapsules for neutron-capture therapy by means of the wurster process
Miyamoto, Masahito,Ichikawa, Hideki,Fukumori, Yoshinobu,Akine, Yasuyuki,Tokuuye, Koichi
, p. 2043 - 2050 (1997)
Gadolinium (Gd)-containing microcapsules designed for neutron-capture therapy (NCT) were prepared by a spouted bed coating process. Microcapsules were designed as a Gd-reservoir. They were prepared with the following properties: particle size was smaller than 50 μm, Gd-content was as high as possible, and release of Gd was suppressed as long as possible. Calcium carbonate (20-32 μm) was selected as a seed particle. As a Gd-source, gadoliniun diethylenetriaminepentaacetic acid (Gd-DTPA) or a synthesized water-insoluble Gd-DTPA derivative, Gd-DTPA-distearylamide (Gd-DTPA-SA), was layered onto the seed particles. The release-suppressing layer was composed of aqueous acrylic latex of 9:9:4 poly(ethyl acrylate/methyl methacrylate]2- hydroxyethyl methacrylate). In preliminary studies, Gd-DTPA microcapsules with 41-45 μm (mass median diameter) were prepared; they released Gd with a short lag-time and 3h-prolongation. Complete release suppression was, however, difficult to achieve because of high water-solubility of Gd-DTPA. Hence, a hydrophobic derivative, Gd-DTPA-SA, was next used as a Gd source. Gd-DTPA-SA microcapsules could he prepared with a mass median diameter of 52 μm. Gd-DTPA-SA content of the microcapsules was 38% and release of Gd was suppressed to less than 0.2% over 60d.
Synthesis and Characterization of GaIII, InIII and LuIII Complexes of a Set of dtpa Bis-Amide Ligands
Greiser, Julia,Hagemann, Tino,Niksch, Tobias,Traber, Philipp,Kupfer, Stephan,Gr?fe, Stefanie,G?rls, Helmar,Weigand, Wolfgang,Freesmeyer, Martin
, p. 4125 - 4137 (2015)
The synthesis and characterization of five new diethylenetriaminepentaacetic acid (dtpa) ligands, (dtpa)-N,N"-bis(alkoxyphenylamide), and their complexation with GaIII, InIII and LuIII are reported. The procedures for the synthesis of all complexes in aqueous media are described as well as a synthetic pathway for the preparation of GaIII complexes in chloroform. All substances were characterized by NMR spectroscopy, mass spectrometry, elemental analysis and HPLC. Single-crystal structure analysis was performed where applicable, which revealed the presence of hepta- and octa-coordinated isomers for InIII complexes and a nine-fold coordination of LuIII ions in the solid state. Additional NMR experiments suggested a hepta-coordinated InIII species in solution, whereas the GaIII complexes appear to be hexa-coordinated and the LuIII complexes to be octa-coordinated. Both NMR and HPLC studies indicated the presence of a single isomer in every complex. The synthesis and characterization of new GaIII, InIII and LuIII complexes of five dtpa bis-amides are described. As determined by single-crystal structure analysis, the InIII complexes are hepta- or octa-coordinated, whereas the LuIII are nona-coordinated in the solid state. NMR studies were undertaken to characterize the coordination behaviour of the complexes in solution.
Platinum(II)-gadolinium(III) complexes as potential single-molecular theranostic agents for cancer treatment
Zhu, Zhenzhu,Wang, Xiaoyong,Li, Tuanjie,Aime, Silvio,Sadler, Peter J.,Guo, Zijian
, p. 13225 - 13228 (2014)
Theranostic agents are emerging multifunctional molecules capable of simultaneous therapy and diagnosis of diseases. We found that platinum(II)-gadolinium(III) complexes with the formula [{Pt(NH3)2Cl}2GdL](NO3)2 possess such properties. The Gd center is stable in solution and the cytoplasm, whereas the Pt centers undergo ligand substitution in cancer cells. The Pt units interact with DNA and significantly promote the cellular uptake of Gd complexes. The cytotoxicity of the Pt-Gd complexes is comparable to that of cisplatin at high concentrations (≥0.1 mm), and their proton relaxivity is higher than that of the commercial magnetic resonance imaging (MRI) contrast agent Gd-DTPA. T1-weighted MRI on B6 mice demonstrated that these complexes can reveal the accumulation of platinum drugs in vivo. Their cytotoxicity and imaging capabilities make the Pt-Gd complexes promising theranostic agents for cancer treatment.
Detection and quantification of lanthanide complexes in cell lysates by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
Corpillo, Davide,Cabella, Claudia,Crich, Simonetta Geninatti,Barge, Alessandro,Aime, Silvio
, p. 6012 - 6016 (2004)
Gadolinium (III) complexes are under intense scrutiny as contrast agents for magnetic resonance imaging. Although currently used mainly as extracellular agents, there is a growing interest to exploit their contrast enhancing ability in the intracellular environment To ascertain the preservation of their chemical integrity upon the intracellular entrapment, it is necessary to have a method for their dosage in the cell lysates. Herein, a mass spectrometric method for detection and quantification of gadolinium complexes in cell lysates is reported. The detection by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) was carried out by using a non-acidic matrix (2,4,6-trihydroxyacetophenone), which does not allow any leakage of gadolinium from the complex. Quantification has been possible by using as an internal standard an ytterbium complex with the same ligand of the analyte. Ytterbium was chosen because, among the lanthanides, it is the one with the isotopic distribution pattern the most similar to that of gadolinium. Sensitivity was enough to detect low micromolar quantities of a cationic complex and high micromolar quantities of a neutral complex in cell lysates of rat hepatoma cells. In the case of anionic complexes, sensitivity was too low for quantitative analysis. To the best of our knowledge, this is the first report concerning the quantification of metal complexes by MALDI-TOF-US.
Synthesis, characterization, thermodynamics stability constant, and relaxation properties of neutral gadolinium(III) complex with derivatives from diethylene triamine pentaacetic acid and m -hydroxybenzoyl hydrazine
Zhang, Ding-Wa,Liu, Yin-Qiu,Yang, Ya-Jun,Zhong, Fan
, p. 882 - 885 (2013)
A novel ligand, diethylenetriamine-N,N″-bis(acetyl-m-hydroxybenzoyl hydrazine)-N, N′, N″-triacetic acid (H3L), was synthesized and characterized on the basis of elemental analysis, molar conductivities, 1H NMR, FAB-MS, TG-DTA analysis, and IR methods. Its complex of Gd(III) holding promise of magnetic resonance imaging(MRI) was synthesized, and relaxivity of GdL and Gd(DTPA)2- used as compare were determined in water solution, respectively. The relaxivity of GdL (R 1 = 6.02 L·mmol-1·s-1) was larger than that of Gd(DTPA)2-(R1 = 4.34L·mmol -1·s-1). The relaxivity of GdL had also been investigated in human serum albumin (HSA) solution, the relaxivity of GdL was enhanced from 6.02 L·mmol-1·s-1 in water solution to 7.10 L·mmol-1·s-1 in HSA solution. In addition, thermodynamics stability constant of GdL complex was determined. The results showed that GdL is a prospective MRI contrast agent, although the thermodynamic stability constant of GdL complex(KGdL = 1019.92) was a little less than that of Gd(DTPA) 2-(KGd-DTPA = 1020.73).
Physicochemical characterization of the dimeric lanthanide complexes [en{Ln(DO3A)(H2O)}2] and [pi{Ln(DTTA)(H 2O)}2]2-: A variable-temperature 17O NMR study
Lee, Tzu-Ming,Cheng, Tsan-Hwang,Ou, Ming-Hung,Chang, C. Allen,Liu, Gin-Chung,Wang, Yun-Ming
, p. 329 - 336 (2004)
The Gd(III) complexes of the two dimeric ligands [en(DO3A)2] {N,N′-bis[1,4,7-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecan-10-yl- methylcarbonyl]-N,N′-ethylenediamme} and [pi(DTTA)2] 8- [bisdiethylene-triaminepentaacetic acid (trans-1,2- cyclohexanediamine)] were synthesized and characterized. The 17O NMR chemical shift of H2O induced by [en{Dy(DO3A)}2] and [pi{Dy(DTTA)}2]2- at pH 6.80 proved the presence of 2.1 and 2.2 inner-sphere water molecules, respectively. Water proton spin-lattice relaxation rates for [en{Gd(DO3A)(H2O)}2] and [pi{Gd(DTTA)(H2O)}2]2- at 37.0 ± 0.1°C and 20 MHz are 3.60 ± 0.05 and 5.25 ± 0.05 mM -1 s-1 per Gd, respectively. The EPR transverse electronic relaxation rate and 17O NMR transverse relaxation time for the exchange lifetime of the coordinated H2O molecule and the 2H NMR longitudinal relaxation rate of the deuterated diamagnetic lanthanum complex for the rotational correlation time were thoroughly investigated, and the results were compared with those reported previously for other lanthanide(III) complexes. The exchange lifetimes for [en{Gd(DO3A)(H 2O)}2] (769 ± 10 ns) and [pi{Gd(DTTA)(H 2O)}2]2- (910 ± 10 ns) are significantly higher than those of [Gd(DOTA)(H2O)]- (243 ns) and [Gd(DTPA)(H2O)]2- (303 ns) complexes. The rotational correlation times for [en{Gd(DO3A)(H2O)}2] (150 ± 11 ps) and [pi{Gd(DTTA)(H2O)}2]2- (130 ± 12 ps) are slightly greater than those of [Gd(DOTA)(H2O)] - (77 ps) and [Gd(DTPA)(H2O)]2- (58 ps) complexes. The marked increase in relaxivity (r1) of [en{Gd(DO3A)(H2O)}2] and [pi{Gd(DTTA)(H 2O)}2]2- result mainly from their longer rotational correlation time and higher molecular weight. Copyright
MRI-guided targeting delivery of doxorubicin with reduction-responsive lipid-polymer hybrid nanoparticles
Wu, Bo,Lu, Shu-Ting,Deng, Kai,Yu, Hui,Cui, Can,Zhang, Yang,Wu, Ming,Zhuo, Ren-Xi,Xu, Hai-Bo,Huang, Shi-Wen
, p. 6871 - 6882 (2017)
In recent years, there has been increasing interest in developing a multifunctional nanoscale platform for cancer monitoring and chemotherapy. However, there is still a big challenge for current clinic contrast agents to improve their poor tumor selectivity and response. Herein, we report a new kind of Gd complex and folate-coated redox-sensitive lipid-polymer hybrid nanoparticle (Gd-FLPNP) for tumor-targeted magnetic resonance imaging and therapy. Gd-FLPNPs can simultaneously accomplish diagnostic imaging, and specific targeting and controlled release of doxorubicin (DOX). They exhibit good monodispersity, excellent size stability, and a well-defined core-shell structure. Paramagnetic nanoparticles based on gadolinium-diethylenetriaminepentaacetic acid-biscetylamine have paramagnetic properties with an approximately two-fold enhancement in the longitudinal relaxivity compared to clinical used Magnevist. For targeted and reduction-sensitive drug delivery, Gd-FLPNPs released DOX faster and enhanced cell uptake in vitro, and exhibited better antitumor effect both in vitro and in vivo.
Luminescent lanthanide(III) complexes of DTPA-bis(amido-phenyl-terpyridine) for bioimaging and phototherapeutic applications
Dasari, Srikanth,Singh, Swati,Abbas, Zafar,Sivakumar, Sri,Patra, Ashis K.
supporting information, (2021/04/12)
We report here a series of coordinatively-saturated and thermodynamically stable luminescent [Ln(dtntp)(H2O)] [Ln(III) = Eu (1), Tb (2), Gd (3), Sm (4) and Dy (5)] complexes using an aminophenyl-terpyridine appended-DTPA (dtntp) chelating ligand as cell imaging and photocytotoxic agents. The N,N″-bisamide derivative of H5DTPA named as dtntp is based on 4′-(4-aminophenyl)-2,2′:6′,2″-terpyridine conjugated to diethylenetriamine-N,N′,N″-pentaacetic acid. The structure, physicochemical properties, detailed photophysical aspects, interaction with DNA and serum proteins, and photocytotoxicity were studied. The intrinsic luminescence of Eu(III) and Tb(III) complexes due to f → f transitions used to evaluate their cellular uptake and distribution in cancer cells. The solid-state structure of [Eu(dtntp)(DMF)] (1·DMF) shows a discrete mononuclear molecule with nine-coordinated {EuN3O6} distorted tricapped-trigonal prism (TTP) coordination geometry around the Eu(III). The {EuN3O6} core results from three nitrogen atoms and three carboxylate oxygen atoms, and two carbonyl oxygen atoms of the amide groups of dtntp ligand. The ninth coordination site is occupied by an oxygen atom of DMF as a solvent from crystallization. The designed probes have two aromatic pendant phenyl-terpyridine (Ph-tpy) moieties as photo-sensitizing antennae to impart the desirable optical properties for cellular imaging and photocytotoxicity. The photostability, coordinative saturation, and energetically rightly poised triplet states of dtntp ligand allow the efficient energy transfer (ET) from Ph-tpy to the emissive excited states of the Eu(III)/Tb(III), makes them luminescent cellular imaging probes. The Ln(III) complexes show significant binding tendency to DNA (K ~ 104 M?1), and serum proteins (BSA and HSA) (K ~ 105 M?1). The luminescent Eu(III) (1) and Tb(III) (2) complexes were utilized for cellular internalization and cytotoxicity studies due to their optimal photophysical properties. The cellular uptake studies using fluorescence imaging displayed intracellular (cytosolic and nuclear) localization in cancer cells. The complexes 1 and 2 displayed significant photocytotoxicity in HeLa cells. These results offer a modular design strategy with further scope to utilize appended N,N,N-donor tpy moiety for developing light-responsive luminescent Ln(III) bioprobes for theranostic applications.
