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.

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.

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.

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.