Gadolinium-Based Hybrid Nanoparticles as a Positive MR Contrast Agent

Hifumi, Hiroki; Yamaoka, Seiichi; Tanimoto, Akihiro; Citterio, Daniel; Suzuki, Kôji

doi:10.1021/ja066442d

Cited by 229 publications

(243 citation statements)

References 28 publications

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“…The r 2 /r 1 of ZES-SPIONs is slightly lower and therefore slightly better than that of VSOP (44), a state-of-the-art SPION-based T 1 contrast agent. The r 2 /r 1 of our ZES-SPIONs is more preferable than that of other SPION-based MRI contrast agents including Feraheme, Resovist, Feridex, Combidex, Supravist, Clariscan, and others (3,8,9,21,46,47). Furthermore, as shown in Fig.…”

mentioning

confidence: 83%

Exceedingly small iron oxide nanoparticles as positive MRI contrast agents

Bruns

Kaul

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

396

322

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Medical imaging is routine in the diagnosis and staging of a wide range of medical conditions. In particular, magnetic resonance imaging (MRI) is critical for visualizing soft tissue and organs, with over 60 million MRI procedures performed each year worldwide. About one-third of these procedures are contrast-enhanced MRI, and gadolinium-based contrast agents (GBCAs) are the mainstream MRI contrast agents used in the clinic. GBCAs have shown efficacy and are safe to use with most patients; however, some GBCAs have a small risk of adverse effects, including nephrogenic systemic fibrosis (NSF), the untreatable condition recently linked to gadolinium (Gd) exposure during MRI with contrast. In addition, Gd deposition in the human brain has been reported following contrast, and this is now under investigation by the US Food and Drug Administration (FDA). To address a perceived need for a Gdfree contrast agent with pharmacokinetic and imaging properties comparable to GBCAs, we have designed and developed zwitterioncoated exceedingly small superparamagnetic iron oxide nanoparticles (ZES-SPIONs) consisting of ∼3-nm inorganic cores and ∼1-nm ultrathin hydrophilic shell. These ZES-SPIONs are free of Gd and show a high T 1 contrast power. We demonstrate the potential of ZES-SPIONs in preclinical MRI and magnetic resonance angiography. exceedingly small iron oxide nanoparticles | renal clearance | gadoliniumfree positive MR contrast agent | preclinical magnetic resonance imaging M RI signal arises from the excitation of low-energy nuclear spins, which are formed in a permanent magnetic field, by applying radiofrequency pulses followed by the measurement of the spin relaxation processes (i.e

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confidence: 83%

Exceedingly small iron oxide nanoparticles as positive MRI contrast agents

Bruns

Kaul

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

396

322

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“…[46] Dextran-coated GdPO 4 nanoparticles (PGP/dextran-K01) were synthesized by a hydrothermal process in the presence of dextran. [47] These Gd-based nanoparticles had significantly low r 2 /r 1 values, and they showed strong positive-contrast effects. However, uniformly sized nanoparticles of gadolinium or related lanthanide compounds have not yet been demonstrated.…”

Section: T1 Nanoparticulate Mri Contrast Agentsmentioning

confidence: 95%

“…The most obvious nanoparticles for T1 agents are gadolinium-based ones, because many gadolinium complexes have been extensively used as clinical MRI contrast agents. Nanoparticles of gadolinium oxide (Gd 2 O 3 ), [45] gadolinium fluoride (GdF 3 ), [46] and gadolinium phosphate (GdPO 4 ) [47] have been investigated as MRI contrast agents. They exhibited signal-enhancing contrast in T1-weighted images with low r 2 /r 1 values.…”

Section: T1 Nanoparticulate Mri Contrast Agentsmentioning

confidence: 99%

Inorganic Nanoparticles for MRI Contrast Agents

2009

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Various inorganic nanoparticles have been used as magnetic resonance imaging (MRI) contrast agents due to their unique properties, such as large surface area and efficient contrasting effect. Since the first use of superparamagnetic iron oxide (SPIO) as a liver contrast agent, nanoparticulate MRI contrast agents have attracted a lot of attention. Magnetic iron oxide nanoparticles have been extensively used as MRI contrast agents due to their ability to shorten T2* relaxation times in the liver, spleen, and bone marrow. More recently, uniform ferrite nanoparticles with high crystallinity have been successfully employed as new T2 MRI contrast agents with improved relaxation properties. Iron oxide nanoparticles functionalized with targeting agents have been used for targeted imaging via the site‐specific accumulation of nanoparticles at the targets of interest. Recently, extensive research has been conducted to develop nanoparticle‐based T1 contrast agents to overcome the drawbacks of iron oxide nanoparticle‐based negative T2 contrast agents. In this report, we summarize the recent progress in inorganic nanoparticle‐based MRI contrast agents.

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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%

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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Gadolinium-Based Hybrid Nanoparticles as a Positive MR Contrast Agent

Cited by 229 publications

References 28 publications

Exceedingly small iron oxide nanoparticles as positive MRI contrast agents

Exceedingly small iron oxide nanoparticles as positive MRI contrast agents

Inorganic Nanoparticles for MRI Contrast Agents

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

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