Ultra‐small gadolinium oxide nanoparticles to image brain cancer cells in vivo with MRI

Abstract

The majority of contrast agents used in magnetic resonance imaging (MRI) is based on the rare-earth element gadolinium. Gadolinium-based nanoparticles could find promising applications in pre-clinical diagnostic procedures of certain types of cancer, such as glioblastoma multiforme. This is one of the most malignant, lethal and poorly accessible forms of cancer. Recent advances in colloidal nanocrystal synthesis have led to the development of ultra-small crystals of gadolinium oxide (US-Gd(2)O(3), 2-3 nm diameter). As of today, this is the smallest and the densest of all Gd-containing nanoparticles. Cancer cells labeled with a sufficient quantity of this compound appear bright in T(1)-weighted MRI images. Here we demonstrate that US-Gd(2)O(3) can be used to label GL-261 glioblastoma multiforme cells, followed by localization and visualization in vivo using MRI. Very high amounts of Gd are efficiently internalized and retained in cells, as confirmed with TEM and ICP-MS. Labeled cells were visualized in vivo at 1.5 T using the chicken embryo model. This is one more step toward the development of "positively contrasted" cell tracking procedures with MRI.

Growth of Gd2O3 nanoparticles inside mesoporous silica frameworks

“…Gadolinium oxide, one of the rare earth oxides, is used as an additive in other ceramics, e.g., Gd 2 O 3 was used to stabilize the tetragonal phase of zirconia [5] and to improve the densification of sintered SiC [6]. At present, attempts are being made to use strongly paramagnetic Gd 2 O 3 nanoparticles for contrast enhancement in magnetic resonance imaging (MRI) [7] and, most recently, Faucher et al [8] reported on the possibility of using ultra-small gadolinium oxide nanoparticles to image brain cancer cells in vivo by MRI.…”

Gd2O3 nanoparticles in hematopoietic cells for MRI contrast enhancement

“…Although the cells, especially Ba/F3, only partly took up the particles, they still were exposed to the Gd extracellularly, as the nanoparticles were not washed away during these observations. Taking this into account, the viability was not significantly reduced and this preserved good viability is confirmed by Faucher et al 22 It is very promising that Ba/F3 cells withstand the Gd and DEG exposure to the same extent as THP-1 (previously studied in Klasson et al 15 However, toxicology investigations of the Gd 2 O 3 nanoparticles need more thorough viability studies and long term biological effects need to be evaluated. In addition, it has to be remembered that before considering …”

MRI with Gadolinium‐Based Nanoparticles

“…However, it was shown in aqueous media that these nanoparticles tend to agglomerate with subsequent decrease in the relaxivity [175]. nonetheless, improved contrast was obtained in the visualization of brain tumors [176] or in the detection of glioblastoma cancer cells in vivo [177]. These particles can furthermore be modified on their surface by incorporation of various functional groups such as organic acids [178] or peG [179], suggesting potential control over stability and biodistribution.…”