Change search
ReferencesLink to record
Permanent link

Direct link
MRI Contrast Enhancement and Cell Labeling using Gd2O3 Nanoparticles
Linköping University, Center for Medical Image Science and Visualization, CMIV. Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences.
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

There is an increasing interest for nanomaterials in bio-medical applications and in this work, nanoparticles of gadolinium oxide (Gd2O3 ) have been investigated as a novel contrast agent for magnetic resonance imaging (MRI). Relaxation properties have been studied in aqueous solutions as well as in cell culture medium and the nanoparticles have been explored as cell labeling agents. The fluorescent properties of the particles were used to visualize the internalization in cells and doped particles were investigated as a multimodal agent that could work as a fluorescent marker for microscopy and as a contrast enhancer for MRI. Fluorescent studies show that the Gd2O3 nanoparticles doped with 5% terbium have interesting fluorescent properties and that these particles could work as such multimodal contrast agent. Relaxivity measurements show that in aqueous solutions, there is a twofold increase in relaxivity for Gd2O3 compared to commercial agent Gd-DTPA. In cell culture medium as well as in cells, there is a clear T1 effect and an increase in signal intensity in T1-mapped images. The cellular uptake of Gd2O3 nanoparticles were increased with the use of transfection agent protamine sulfate. This work shows that Gd2O3 nanoparticles possess good relaxation properties that are retained in different biological environments. Gd2O3 particles are suitable as a T1 contrast agent, but seem also be adequate for T2 enhancement in forinstance cell labeling experiments.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press , 2011. , 73 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1230
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-68802ISBN: 978-91-7393-215-8OAI: oai:DiVA.org:liu-68802DiVA: diva2:421094
Public defence
2011-06-08, Wrannesalen, Universitetssjukhuset, CMIV, Campus US, Linköpings universitet, Linköping, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2011-06-07 Created: 2011-06-07 Last updated: 2013-09-05Bibliographically approved
List of papers
1. High Proton Relaxivity for Gadolinium Oxide Nanoparticles
Open this publication in new window or tab >>High Proton Relaxivity for Gadolinium Oxide Nanoparticles
Show others...
2006 (English)In: Magnetic Resonance Materials in Physics, Biology and Medicine, ISSN 0968-5243, E-ISSN 1352-8661, Vol. 19, no 4, 180-186 p.Article in journal (Refereed) Published
Abstract [en]

Objective: Nanosized materials of gadolinium oxide can provide high-contrast enhancement in magnetic resonance imaging (MRI). The objective of the present study was to investigate proton relaxation enhancement by ultrasmall (5 to 10 nm) Gd2O3 nanocrystals.

Materials and methods: Gd2O3 nanocrystals were synthesized by a colloidal method and capped with diethylene glycol (DEG). The oxidation state of Gd2O3 was confirmed by X-ray photoelectron spectroscopy. Proton relaxation times were measured with a 1.5-T MRI scanner. The measurements were performed in aqueous solutions and cell culture medium (RPMI).

Results: Results showed a considerable relaxivity increase for the Gd2O3–DEG particles compared to Gd-DTPA. Both T 1 and T 2 relaxivities in the presence of Gd2O3–DEG particles were approximately twice the corresponding values for Gd–DTPA in aqueous solution and even larger in RPMI. Higher signal intensity at low concentrations was predicted for the nanoparticle solutions, using experimental data to simulate a T1-weighted spin echo sequence.

Conclusion: The study indicates the possibility of obtaining at least doubled relaxivity compared to Gd–DTPA using Gd2O3–DEG nanocrystals as contrast agent. The high T 1 relaxation rate at low concentrations of Gd2O3 nanoparticles is very promising for future studies of contrast agents based on gadolinium-containing nanocrystals.

Keyword
Gd2O3, Nanoparticle, Contrast agent, Relaxivity, MRI
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-12943 (URN)10.1007/s10334-006-0039-x (DOI)000241584400002 ()
Available from: 2008-02-21 Created: 2008-02-21 Last updated: 2015-10-09
2. Positive MRI Enhancement in THP-1 Cells with Gd2O3 Nanoparticles
Open this publication in new window or tab >>Positive MRI Enhancement in THP-1 Cells with Gd2O3 Nanoparticles
Show others...
2008 (English)In: Contrast Media and Molecular Imaging, ISSN 1555-4309, Vol. 3, no 3, 106-111 p.Article in journal (Refereed) Published
Abstract [en]

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, (pr1 = 0.36), but r2 was significantly different for the two different series (pr2 = 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.

Keyword
gadolinium oxide, nanoparticles, contrast agent, THP-1 cells, magnetic resonance imaging
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-12945 (URN)10.1002/cmmi.236 (DOI)000257982000002 ()
Available from: 2008-02-21 Created: 2008-02-21 Last updated: 2015-10-09Bibliographically approved
3. Detection of Gd2O3 Nanoparticles in Hematopoietic Cells for MRI Contrast Enhancement
Open this publication in new window or tab >>Detection of Gd2O3 Nanoparticles in Hematopoietic Cells for MRI Contrast Enhancement
Show others...
(English)Manuscript (preprint) (Other academic)
Abstract [en]

As the utility of magnetic resonance imaging (MRI) broadens, the importance of having specific and efficient contrast agents increases and 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. The Gd2O3 nanoparticles are also promising for MRI cell tracking. The aim of the present work was to study cell labeling with Gd2O3 nanoparticles and to improve techniques for monitoring hematopoietic stem cell migration by MRI.

We studied particle uptake in two cell lines; the hematopoietic progenitor cell line Ba/F3 and the monocytic cell line THP-1. Cells were incubated with Gd2O3 nanoparticles as well as superparamagnetic iron oxide particles (SPIOs) for comparison. In addition, it was investigated whether the transfection agent protamine sulfate increased the particle uptake. Treated cells were examined by microscopic techniques, MRI and analyzed for particle content.

Results showed that particles were intracellular, however in Ba/F3 only sparsely. The relaxation times were shortened with increasing particle concentration. Overall relaxivities, r1 and r2 for Gd2O3 nanoparticles in all cell samples measured were 5.1 ± 0.3 and 14.9 ± 0.7 (s-1mM-1) respectively. Goodness of fit was 0.97 in both cases. Protamine sulfate treatment increased the uptake in both Ba/F3 cells and THP-1 cells.

Viability of treated cells was not significantly decreased and thus, we conclude that the use of Gd2O3 nanoparticles is suitable for this type of cell labeling by means of detecting and monitoring hematopoietic cells.

Keyword
Gadolinium oxide; nanoparticles; magnetic resonance imaging; Ba/F3 cells, THP-1 cells.
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-68801 (URN)
Available from: 2011-06-07 Created: 2011-06-07 Last updated: 2013-09-04Bibliographically approved
4. Synthesis and Characterization of Tb3+-Doped Gd2O3 Nanocrystals: A Bifunctional Material with Combined Fluorescent Labeling and MRI Contrast Agent Properties
Open this publication in new window or tab >>Synthesis and Characterization of Tb3+-Doped Gd2O3 Nanocrystals: A Bifunctional Material with Combined Fluorescent Labeling and MRI Contrast Agent Properties
Show others...
2009 (English)In: The Journal of Physical Chemistry C, ISSN 1932-7447, E-ISSN 1932-7455, Vol. 113, no 17, 6913-6920 p.Article in journal (Refereed) Published
Abstract [en]

Ultrasmall gadolinium oxide nanoparticles doped with terbium ions were synthesized by the polyol route and characterized as a potentially bifunctional material with both fluorescent and magnetic contrast agent properties. The structural, optical, and magnetic properties of the organic-acid-capped and PEGylated Gd2O3:Tb3+ nanocrystals were studied by HR-TEM, XPS, EDX, IR, PL, and SQUID. The luminescent/fluorescent property of the particles is attributable to the Tb3+ ion located on the crystal lattice of the Gd2O3 host. The paramagnetic behavior of the particles is discussed. Pilot studies investigating the capability of the nanoparticles for fluorescent labeling of living cells and as a MRI contrast agent were also performed. Cells of two cell lines (THP-1 cells and fibroblasts) were incubated with the particles, and intracellular particle distribution was visualized by confocal microscopy. The MRI relaxivity of the PEGylated nanoparticles in water at low Gd concentration was assessed showing a higher T-1 relaxation rate compared to conventional Gd-DTPA chelates and comparable to that of undoped Gd2O3 nanoparticles.

National Category
Natural Sciences
Identifiers
urn:nbn:se:liu:diva-12944 (URN)10.1021/jp808708m (DOI)000265529700009 ()
Note

On the day of the defence date the status of this article was Submitted

Available from: 2008-02-21 Created: 2008-02-21 Last updated: 2015-10-09Bibliographically approved

Open Access in DiVA

MRI Contrast Enhancement and Cell Labeling using Gd2O3 Nanoparticles(750 kB)1690 downloads
File information
File name FULLTEXT01.pdfFile size 750 kBChecksum SHA-512
a4db041b5a9b2daf0f51ec82a81b3acd175cf350d72d3471d99b798ab375917c38ee203cc2eec56598ab8ab58201c1b2a210e9c3f4994fcc3c0d37020be14d57
Type fulltextMimetype application/pdf
omslag(3435 kB)67 downloads
File information
File name COVER01.pdfFile size 3435 kBChecksum SHA-512
ea2018000f506fecbf544e497cfd11d01f18ad066826ac4503585ada7c43ec44961b36369e0f74b4a6a0edd28c2996c51f36154d615b87c9b041324693e55370
Type coverMimetype application/pdf

Search in DiVA

By author/editor
Hedlund, Anna
By organisation
Center for Medical Image Science and Visualization, CMIVRadiologyFaculty of Health Sciences
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
Total: 1690 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Total: 624 hits
ReferencesLink to record
Permanent link

Direct link