Water‐Soluble <i>Ultra Small</i> Paramagnetic or Superparamagnetic Metal Oxide Nanoparticles for Molecular MR Imaging

Park, Ja Young; Choi, Eunsuk; Baek, Myung Ju; Lee, Gang Ho; Woo, Sung-Ho; Chang, Yongmin

doi:10.1002/ejic.200900173

Cited by 54 publications

(58 citation statements)

References 21 publications

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“…Consequently, they produce hypointense signals in T 2 -and T 2 *-weighted images, 32 and thus the affected regions appear darker. The phenomenon can be said to result from the large heterogeneity of the magnetic field around the nanoparticle through which water molecules diffuse, since diffusion induces dephasing of the proton magnetic moments, resulting in T 2 shortening.…”

Section: T 2 Contrast Agentsmentioning

confidence: 99%

Nanoparticles in magnetic resonance imaging: from simple to dual contrast agents

Estelrich¹,

Sánchez-Martín²,

Busquets³

2015

IJN

281

106

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Magnetic resonance imaging (MRI) has become one of the most widely used and powerful tools for noninvasive clinical diagnosis owing to its high degree of soft tissue contrast, spatial resolution, and depth of penetration. MRI signal intensity is related to the relaxation times ( T 1 , spin–lattice relaxation and T 2 , spin–spin relaxation) of in vivo water protons. To increase contrast, various inorganic nanoparticles and complexes (the so-called contrast agents) are administered prior to the scanning. Shortening T 1 and T 2 increases the corresponding relaxation rates, 1/ T 1 and 1/ T 2 , producing hyperintense and hypointense signals respectively in shorter times. Moreover, the signal-to-noise ratio can be improved with the acquisition of a large number of measurements. The contrast agents used are generally based on either iron oxide nanoparticles or ferrites, providing negative contrast in T 2 -weighted images; or complexes of lanthanide metals (mostly containing gadolinium ions), providing positive contrast in T 1 -weighted images. Recently, lanthanide complexes have been immobilized in nanostructured materials in order to develop a new class of contrast agents with functions including blood-pool and organ (or tumor) targeting. Meanwhile, to overcome the limitations of individual imaging modalities, multimodal imaging techniques have been developed. An important challenge is to design all-in-one contrast agents that can be detected by multimodal techniques. Magnetoliposomes are efficient multimodal contrast agents. They can simultaneously bear both kinds of contrast and can, furthermore, incorporate targeting ligands and chains of polyethylene glycol to enhance the accumulation of nanoparticles at the site of interest and the bioavailability, respectively. Here, we review the most important characteristics of the nanoparticles or complexes used as MRI contrast agents.

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Section: T 2 Contrast Agentsmentioning

confidence: 99%

Nanoparticles in magnetic resonance imaging: from simple to dual contrast agents

Estelrich¹,

Sánchez-Martín²,

Busquets³

2015

IJN

281

106

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“…; Fortin et al 2007;McDonald and Watkin 2006;Park et al 2009;Söderlind et al 2005;Petoral Jr et al 2009;Kim et al 2010), gadolinium fluoride (GdF 3 ) (Evanics et al 2006;Chaput et al 2011) or gadolinium phosphate (GdPO 4 ) (Hifumi et al 2006;Yan et al 2010;Lai et al 2008). The crystals preferably are kept small enough to give a large surface to bulk ratio and thereby an efficient interaction between Gd 3+ and water molecules; i.e a high water exchange.…”

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confidence: 99%

“…The crystals preferably are kept small enough to give a large surface to bulk ratio and thereby an efficient interaction between Gd 3+ and water molecules; i.e a high water exchange. Small or ultrasmall Gd 2 O 3 nanoparticles synthesized according to the polyol route have been extensively studied, by our group and others (Bridot et al 2007;Fortin et al 2007;McDonald and Watkin 2006;Park et al 2009;Petoral Jr et al 2009;Söderlind et al 2005). The yield of the polyol synthesis is rather low though, and a severe drawback is the necessity to apply lengthy dialysis times to purify the nanoparticle solutions from free Gd 3+ .…”

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confidence: 99%

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

et al. 2012

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In all kinds of gadolinium based contrast agents, the presence of free gadolinium ions have to be avoided due to the cytotoxicity. The conventional way of producing a gadolinium based contrast agent is to form a chelate, i.e. stabilizing the metal ion using a chelating agent (for example DTPA or DOTA) but recently nanoparticles is an initial step towards biocompatible and directed nanoparticles.The main focus is on a material that in the nearby future will be the core of an The experimental results are supported by theoretical modeling studies.Theoretical IR spectra of three different Gd acetate complexes are presented as well as calculated NEXAFS spectra of one of the Gd acetate complexes and an isolated acetate group. These calculations were performed to elucidate the molecular capping of the synthesized particles. 5 EXPERIMENTAL DETAILS ChemicalsAll chemicals were used as received. Gadolinium(III) acetate hydrate (SigmaAldrich, 99.9 %), tetramethylammonium hydroxide (Sigma-Aldrich, >97 % ), ethyl acetate (Fisher Scientific, 99.99 %), dimethyl sulfoxide (Merck, 99.9 %), ammonium acetate (Merck, >96%), ethanol (Kemetyl, 99.5 %). For preparation of water based solutions, Milli-Q water (ρ > 18.2 MΩ) was used. A commercial gadolinium oxide nanopowder (Aldrich, < 100 nm, 99.8 %) was used as a reference. Preparation of Gd 2 O 3 nanoparticlesThe preparation of Gd 2 O 3 nanoparticles was based on a method previously used for producing nanocrystalline ZnO (Schwartz et al. 2003). As Zn 2+ is divalent and Ethyl acetate was added and the mixture was centrifuge washed (3500 rpm) at least three times with ethyl acetate before it was diluted in deionized water. A total amount of 0.28 g ammonium acetate was added to one whole batch to increase the water solubility. Powder samples were air dried. The yield of the sample is dependent on the washing procedure. The gadolinium content after three times of centrifuge washing with ethyl acetate is roughly 60-65 % of the initial amount added in the synthesis.6 Instrumentation X-ray diffraction XRD measurements were carried out with a Philips XRD powder diffractometer using Cu Kα radiation (λ = 1.5418 Å, 40kV, 40 mA). The 2θ step-size was 0.025° and the time per step 4 s. Air dried powder samples were used in the preparation.High-resolution transmission electron microscopy TEM measurements were performed on a FEI Tecnai G 2 electron microscope operated at 200 kV. Sample preparation was done by letting 1-2 drops of Gd 2 O 3 in water dry on an amorphous carbon-covered copper grid.Dynamic light scattering DLS measurements were carried out on an ALV/DLS/SLS-5022F system from ALV-GmbH, Langen Germany, using a HeNe laser at 632.8 nm with 22 mW output power. Prior to the measurements, the samples were temperature stabilized in a thermostat bath at 22.1 °C for at least 10 minutes. The scattering angle was 90°. 15 Gd 2 O 3 samples dispersed in MilliQ water were studied in DLS, and the long term stability of the suspensions were studied by repeated measurements during a period of 6 weeks.ζ Pot...

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“…This is likely to be, because r 1 and r 2 are determined by the material with a higher relaxivity. Gd III ions close to the nanoparticle surface mainly contribute to r 1 , whereas the surface-doped MnO mainly contributes to r 2 , because r 1 (Gd 2 O 3 ) Ͼ r 1 (MnO) [29] and r 2 (Gd 2 O 3 ) Ͻ r 2 (MnO). This shows that r 2 can be improved by doping with a metal oxide with a high r 2 value at the same time as keeping the r 1 value of the ultra-small Gd 2 O 3 nanoparticles.…”

Section: In-vitro Map Images and Relaxivitiesmentioning

confidence: 98%

Water‐Soluble Ultra‐Small Manganese Oxide Surface Doped Gadolinium Oxide (Gd₂O₃@MnO) Nanoparticles for MRI Contrast Agent

et al. 2010

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We have developed ultra‐small gadolinium oxide (Gd2O3) nanoparticles, which are surface‐doped with manganese oxide (MnO) (abbreviated as Gd2O3@MnO). The surface‐doped nanoparticles ranged from 1 to 2 nm in diameter. They were further coated with hydrophilic biocompatible lactobionic acid. In‐vitro tests of the sample solution indicated clear dose‐dependent contrast enhancements in both T1 and T2 map images, showing that the nanoparticles may be used as both T1 and T2 MRI contrast agents. Their performance as a T1 MRI contrast agent was proved in vivo through T1 MR images of a mouse.

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Water‐Soluble Ultra Small Paramagnetic or Superparamagnetic Metal Oxide Nanoparticles for Molecular MR Imaging

Cited by 54 publications

References 21 publications

Nanoparticles in magnetic resonance imaging: from simple to dual contrast agents

Nanoparticles in magnetic resonance imaging: from simple to dual contrast agents

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

Water‐Soluble Ultra‐Small Manganese Oxide Surface Doped Gadolinium Oxide (Gd₂O₃@MnO) Nanoparticles for MRI Contrast Agent

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Water‐Soluble Ultra Small Paramagnetic or Superparamagnetic Metal Oxide Nanoparticles for Molecular MR Imaging

Cited by 54 publications

References 21 publications

Nanoparticles in magnetic resonance imaging: from simple to dual contrast agents

Nanoparticles in magnetic resonance imaging: from simple to dual contrast agents

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

Water‐Soluble Ultra‐Small Manganese Oxide Surface Doped Gadolinium Oxide (Gd2O3@MnO) Nanoparticles for MRI Contrast Agent

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Water‐Soluble Ultra‐Small Manganese Oxide Surface Doped Gadolinium Oxide (Gd₂O₃@MnO) Nanoparticles for MRI Contrast Agent