Synthesis and Characterization of PEGylated Gd<sub>2</sub>O<sub>3</sub> Nanoparticles for MRI Contrast Enhancement

Ahrén, Maria; Selegård, Linnéa; Klasson, Anna; Söderlind, Fredrik; Abrikossova, Natalia; Skoglund, Camilla; Bengtsson, Torbjörn; Engström, Maria; Käll, Per-Olov; Uvdal, Kajsa

doi:10.1021/la903566y

Cited by 200 publications

(181 citation statements)

References 44 publications

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“…where more Gd surface atoms are thus able to interact with hydrogen protons. Ahrén et al [12] and Hu et al [13] reported a water relaxivity increment of a factor of 2 per Gd atom for Gd2O3 nanoparticles, compared to Magnevist .…”

Section: Contrast Agents For Magnetic Resonance Imagingmentioning

confidence: 98%

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Evaluation of the Dual-Modal usage of contrast agents by means of Synchrotron X-ray Computed Microtomography and Magnetic Resonance Imaging using Macrophages loaded with Barium Sulfate and Gadolinium Nanoparticles for Detection and Monitoring in Animal Disease Models

Larsson

2015

Linköping Studies in Science and Technology. Dissertations

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To My Family. A B S T R A C TTechnical improvements of imaging devices during the last two decades have led to the development of so called hybrid imaging modalities, containing at least two different imaging modalities in the same machine. Hybrid imaging allows the combination of multi-modal images and the extraction of both complementary and synergistic information, which is useful for more accurate and reliable diagnosis. Within this framework there was an increased need for multi-modal contrast agents. During the last decade development of multi-modal contrast agents have hence received further attention.Recent developments of X-ray based imaging techniques now also offers imaging in other regimes, than standard absorption based imaging, e.g. phase contrast imaging, which exploits the refraction and phase-shift of the incident X-ray beam at tissue-interfaces. It has been shown that phase contrast imaging is more sensitive than classical clinical radiography, especially in soft-tissue applications, such as mammography.This thesis focuses on evaluating the dual-modal Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) capabilities of contrast agents. For such purposes a gadolinium based contrast agent is of high interest, due to its paramagnetic properties, which while present inside a magnetic field will hence interact with the protons spins of water (in tissue and fat) and shorten their the T1 relaxation time, thereby creating a positive image contrast in MRI. Furthermore, the X-ray Mass Attenuation Coefficient (MAC) of gadolinium is relatively high, thus suggesting its potential use, also as a CT contrast agent.Gadolinium nanoparticles can be loaded into cells, such as macrophages, which offers the possibility to track cells inside entire organisms. In the first step the uptake of gadolinium nanoparticles inside cells was investigated, together with a test for toxicity. To show the potential of using gadolinium nanoparticle loaded macrophages for functional imaging of inflammation, an acute allergic airway inflammation mouse model (mimicking asthma in humans) was used and analyzed by in-situ synchrotron phase contrast CT. This animal model was chosen, since macrophages are one of the main effector cells in asthma, where especially their ability to migrate is of crucial interest, which up until now was not possible to study in-situ. v In the first step this approach was evaluated using macrophages loaded with a clinical contrast agent containing barium sulphate, since this agent is known to provide high contrast in CT. In the ultimate step a combination of both barium sulphate and gadolinium nanoparticle loaded macrophages was used in the same mouse model (mimicking human asthma) and analyzed by dual modal Synchrotron phase contrast CT and Micro Magnetic Resonance Imaging (µ-MRI).Complementary results in terms of the biodistribution of injected macrophages could only be obtained by the combination of both synchrotron phase contrast CT and µ-MRI, where the first modality allows a detailed local...

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Section: Contrast Agents For Magnetic Resonance Imagingmentioning

confidence: 98%

“…Marinescu et al [19] [20]) and a positive MR contrast agent based on Gadolinium Oxide nanoparticles (GdO-NP) (hereinafter referred to as GdNP) [12] were tested as intracellular contrast agents in an animal disease model of asthma.…”

Section: Selection and Development Of A Multi-modal Contrast Agent Fomentioning

confidence: 99%

Evaluation of the Dual-Modal usage of contrast agents by means of Synchrotron X-ray Computed Microtomography and Magnetic Resonance Imaging using Macrophages loaded with Barium Sulfate and Gadolinium Nanoparticles for Detection and Monitoring in Animal Disease Models

Larsson

2015

Linköping Studies in Science and Technology. Dissertations

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“…For further details, see earlier published data. 6,8,15 Gd 2 O 3 -DEG particles have earlier been characterized by transmission electron microscopy showing crystalline particles with an average size of about 2-5 nm. 9,16 In this work, crystalline particles in the same size range were obtained.…”

Section: Particle Characterizationmentioning

confidence: 99%

“…For this reason, Gd oxide (Gd 2 O 3 ) nanoparticles have gained attention. [6][7][8] In contrast to superparamagnetic iron oxide particles, Gd 2 O 3 can easily generate positive contrast, thereby avoiding loss of signal and image voids that generally occur when using susceptibility contrast agents. Such signal loss could make it difficult to detect the contrast agent and discriminate between the agent, tissue, and image artifacts.…”

Section: Introductionmentioning

confidence: 99%

Gd2O3 nanoparticles in hematopoietic cells for MRI contrast enhancement

Hedlund

Ahrén²,

Gustafsson³

et al. 2011

IJN

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As the utility of magnetic resonance imaging (MRI) broadens, the importance of having specific and efficient contrast agents increases and in recent time there has been a huge development in the fields of molecular imaging and intracellular markers. Previous studies have shown that gadolinium oxide (Gd2O3) nanoparticles generate higher relaxivity than currently available Gd chelates: In addition, the Gd2O3 nanoparticles have promising properties for MRI cell tracking. The aim of the present work was to study cell labeling with Gd2O3 nanoparticles in hematopoietic cells and to improve techniques for monitoring hematopoietic stem cell migration by MRI. Particle uptake was studied in two cell lines: the hematopoietic progenitor cell line Ba/F3 and the monocytic cell line THP-1. Cells were incubated with Gd2O3 nanoparticles and it was investigated whether the transfection agent protamine sulfate increased the particle uptake. Treated cells were examined by electron microscopy and MRI, and analyzed for particle content by inductively coupled plasma sector field mass spectrometry. Results showed that particles were intracellular, however, sparsely in Ba/F3. The relaxation times were shortened with increasing particle concentration. Relaxivities, r1 and r2 at 1.5 T and 21°C, for Gd2O3 nanoparticles in different cell samples were 3.6–5.3 s-1 mM-1 and 9.6–17.2 s-1 mM-1, respectively. Protamine sulfate treatment increased the uptake in both Ba/F3 cells and THP-1 cells. However, the increased uptake did not increase the relaxation rate for THP-1 as for Ba/F3, probably due to aggregation and/or saturation effects. Viability of treated cells was not significantly decreased and thus, it was concluded that the use of Gd2O3 nanoparticles is suitable for this type of cell labeling by means of detecting and monitoring hematopoietic cells. In conclusion, Gd2O3 nanoparticles are a promising material to achieve positive intracellular MRI contrast; however, further particle development needs to be performed.

funding agencies|Swedish Research Council| 621-2007-3810 621-2009-5148 521-2009-3423 |VINNOVA| 2009-00194 |Center in Nanoscience and Technology at LiTH (CeNano)||

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“…These molecular magnets are used as contrast agents in magnetic resonance imaging, and have shown an efficacy 40 to 90 times larger than any other Gd 3þ -based contrast agent. 2,5,6 The maximum magnetic moment of gadolinium is 7l B which is about two times larger than those of the 3d metals Fe, Ni, and Co. Therefore, molecular magnets based on Gd metal are expected to show enhanced magnetoresponsive properties relative to those based on 3d-metals.…”

Section: Introductionmentioning

confidence: 99%

Magnetic properties and phase transitions of gadolinium-infused carbon nanotubes

Quetz

Dubenko

Samanta

et al. 2013

Journal of Applied Physics

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Carbon nanotube (CNT)/metal-cluster-based composites are envisioned as new materials that possess unique electronic properties which may be utilized in a variety of future applications. Superparamagnetic behavior was reported for CNTs with Gd ions introduced into the CNT openings by internal loading with an aqueous GdCl 3 chemical process. In the current work, the magnetic properties of the CNT/Gd composites were obtained by the joining and annealing of Gd metal and CNTs at 850 C for 48 h. Energy dispersive X-ray analysis shows the presence of Gd intermingled with the CNT walls with maximum and average Gd concentrations of about 20% and 4% (by weight), respectively. The Gd clusters have a non-uniform distribution and are mostly concentrated at the ends of the CNTs. A ferromagnetic-type transition at T C $ 320 K, accompanied by jump like change in magnetization and temperature hysteresis typical for the temperature induced first order phase transitions has been observed by magnetization measurements. It was found that Gd infused into the CNTs by the annealing results in a first order paramagnetic-ferromagnetic transition at T C ¼ 320 K. V C 2013 American Institute of Physics. [http://dx

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Synthesis and Characterization of PEGylated Gd₂O₃ Nanoparticles for MRI Contrast Enhancement

Cited by 200 publications

References 44 publications

Evaluation of the Dual-Modal usage of contrast agents by means of Synchrotron X-ray Computed Microtomography and Magnetic Resonance Imaging using Macrophages loaded with Barium Sulfate and Gadolinium Nanoparticles for Detection and Monitoring in Animal Disease Models

Evaluation of the Dual-Modal usage of contrast agents by means of Synchrotron X-ray Computed Microtomography and Magnetic Resonance Imaging using Macrophages loaded with Barium Sulfate and Gadolinium Nanoparticles for Detection and Monitoring in Animal Disease Models

Gd2O3 nanoparticles in hematopoietic cells for MRI contrast enhancement

Magnetic properties and phase transitions of gadolinium-infused carbon nanotubes

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Synthesis and Characterization of PEGylated Gd2O3 Nanoparticles for MRI Contrast Enhancement

Cited by 200 publications

References 44 publications

Evaluation of the Dual-Modal usage of contrast agents by means of Synchrotron X-ray Computed Microtomography and Magnetic Resonance Imaging using Macrophages loaded with Barium Sulfate and Gadolinium Nanoparticles for Detection and Monitoring in Animal Disease Models

Evaluation of the Dual-Modal usage of contrast agents by means of Synchrotron X-ray Computed Microtomography and Magnetic Resonance Imaging using Macrophages loaded with Barium Sulfate and Gadolinium Nanoparticles for Detection and Monitoring in Animal Disease Models

Gd2O3 nanoparticles in hematopoietic cells for MRI contrast enhancement

Magnetic properties and phase transitions of gadolinium-infused carbon nanotubes

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Product

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Synthesis and Characterization of PEGylated Gd₂O₃ Nanoparticles for MRI Contrast Enhancement