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Cerium oxide nanoparticles with integrated gadolinium have been proved to be useful as contrast agents in magnetic resonance imaging. Of question is their performance in dual-energy computed tomography. The aims of this work are to determine (1) the relation between the computed tomography number and the concentration of the I, Gd or Ce contrast agent and (2) under what conditions it is possible to resolve the type of contrast agent. Hounsfield values of iodoacetic acid, gadolinium acetate and cerium acetate dissolved in water at molar concentrations of 10, 50 and 100 mM were measured in a water phantom using the Siemens SOMATOM Definition Force scanner; gadolinium- and cerium acetate were used as substitutes for the gadolinium-integrated cerium oxide nanoparticles. The relation between the molar concentration of the I, Gd or Ce contrast agent and the Hounsfield value was linear. Concentrations had to be sufficiently high to resolve the contrast agents., (© The Author(s) 2021. Published by Oxford University Press.)

Uniform, highly water-dispersible and ultra-small Fe3O4 nanoparticles were synthesized via a modified one-step coprecipitation approach. The prepared Fe3O4 nanoparticles not only show good magnetic properties, long-term stability in a biological environment, but also exhibit good biocompatibility in cell viability and hemolysis assay. Due to the ultra-small sized and highly water-dispersibility, they exhibit excellent relaxivity properties, the 1.7 nm sized Fe3O4 nanoparticles reveal a low r2/r1 ratio of 2.03 (r1 = 8.20 mM(-1) s(-1), r2 = 16.67 mM(-1) s(-1)); and the 2.2 nm sized Fe3O4 nanoparticles also appear to have a low r2/r1 ratio of 4.65 (r1 = 6.15 mM(-1) s(-1), r2 = 28.62 mM(-1) s(-1)). This demonstrates that the proposed ultra-small Fe3O4 nanoparticles have great potential as a new type of T1 magnetic resonance imaging contrast agents. Especially, the 2.2 nm sized Fe3O4 nanoparticles, have a competitive r1 value and r2 value compared to commercial contrasting agents such as Gd-DTPA (r1 = 4.8 mM(-1) s (-1)), and SHU-555C (r2 = 69 mM(-1) s(-1)). In vitro and in vivo imaging experiments, show that the 2.2 nm sized Fe3O4 nanoparticles exhibit great contrast enhancement, long-term circulation, and low toxicity, which enable these ultra-small sized Fe3O4 nanoparticles to be promising as T1 and T2 dual contrast agents in clinical settings.

Water-dispersible and luminescent gadolinium oxide (GO) nanoparticles (NPs) were designed and synthesized for potential dual-modal biological imaging. They were obtained by capping gadolinium oxide nanoparticles with a fluorescent glycol-based conjugated carboxylate (HL). The obtained nanoparticles (GO-L) show long-term colloidal stability and intense blue fluorescence. In addition, L can sensitize the luminescence of europium(III) through the so-called antenna effect. Thus, to extend the spectral ranges of emission, europium was introduced into L-modified gadolinium oxide nanoparticles. The obtained EuIII-doped particles (Eu:GO-L) can provide visible red emission, which is more intensive than that without L capping. The average diameter of the monodisperse modified oxide cores is about 4 nm. The average hydrodynamic diameter of the L-modified nanoparticles was estimated to be about 13 nm. The nanoparticles show effective longitudinal water proton relaxivity. The relaxivity values obtained for GO-L and Eu:GO-L were r1=6.4 and 6.3 s−1 mM−1 with r2/r1 ratios close to unity at 1.4 T. Longitudinal proton relaxivities of these nanoparticles are higher than those of positive contrast agents based on gadolinium complexes such as Gd-DOTA, which are commonly used for clinical magnetic resonance imaging. Moreover, these particles are suitable for cellular imaging and show good biocompatibility.

Recently, much attention has been given to the development of biofunctionalized nanoparticles with magnetic properties for novel biomedical imaging. Guided, smart, targeting nanoparticulate magnetic resonance imaging (MRI) contrast agents inducing high MRI signal will be valuable tools for future tissue specific imaging and investigation of molecular and cellular events. In this study, we report a new design of functionalized ultrasmall rare earth based nanoparticles to be used as a positive contrast agent in MRI. The relaxivity is compared to commercially available Gd based chelates. The synthesis, PEGylation, and dialysis of small (3-5 nm) gadolinium oxide (DEG-Gd(2)O(3)) nanoparticles are presented. The chemical and physical properties of the nanomaterial were investigated with Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, transmission electron microscopy, and dynamic light scattering. Neutrophil activation after exposure to this nanomaterial was studied by means of fluorescence microscopy. The proton relaxation times as a function of dialysis time and functionalization were measured at 1.5 T. A capping procedure introducing stabilizing properties was designed and verified, and the dialysis effects were evaluated. A higher proton relaxivity was obtained for as-synthesized diethylene glycol (DEG)-Gd(2)O(3) nanoparticles compared to commercial Gd-DTPA. A slight decrease of the relaxivity for as-synthesized DEG-Gd(2)O(3) nanoparticles as a function of dialysis time was observed. The results for functionalized nanoparticles showed a considerable relaxivity increase for particles dialyzed extensively with r(1) and r(2) values approximately 4 times the corresponding values for Gd-DTPA. The microscopy study showed that PEGylated nanoparticles do not activate neutrophils in contrast to uncapped Gd(2)O(3). Finally, the nanoparticles are equipped with Rhodamine to show that our PEGylated nanoparticles are available for further coupling chemistry, and thus prepared for targeting purposes. The long term goal is to design a powerful, directed contrast agent for MRI examinations with specific targeting possibilities and with properties inducing local contrast, that is, an extremely high MR signal at the cellular and molecular level.

There is a demand for more efficient and tissue-specific MRI contrast agents and recent developments involve the design of substances useful as molecular markers and magnetic tracers. In this study, nanoparticles of gadolinium oxide (Gd2O3) have been investigated for cell labeling and capacity to generate a positive contrast. THP-1, a monocytic cell line that is phagocytic, was used and results were compared with relaxivity of particles in cell culture medium (RPMI 1640). The results showed that Gd2O3-labeled cells have shorter T1 and T2 relaxation times compared with untreated cells. A prominent difference in signal intensity was observed, indicating that Gd2O3 nanoparticles can be used as a positive contrast agent for cell labeling. The r1 for cell samples was 4.1 and 3.6 s(-1) mm(-1) for cell culture medium. The r2 was 17.4 and 12.9 s(-1) mm(-1), respectively. For r1, there was no significant difference in relaxivity between particles in cells compared to particles in cell culture medium, (p(r1) = 0.36), but r2 was significantly different for the two different series (p(r2) = 0.02). Viability results indicate that THP-1 cells endure treatment with Gd2O3 nanoparticles for an extended period of time and it is therefore concluded that results in this study are based on viable cells., (Copyright 2008 John Wiley & Sons, Ltd.)