Gadolinium-conjugated TiO2-DNA oligonucleotide nanoconjugates show prolonged intracellular retention period and T1-weighted contrast enhancement in magnetic resonance images.

Nanoconjugates composed of titanium dioxide (TiO2) nanoparticles, DNA oligonucleotides, and a gadolinium (Gd) contrast agent were synthesized for use in magnetic resonance imaging. Transfection of cultured cancer cells with these nanoconjugates showed them to be superior to the free contrast agent of the same formulation with regard to intracellular accumulation, retention, and subcellular localization. Our results have shown that 48 hours after treatment, the concentration of Gd in nanoconjugate-treated cells was 1000-fold higher than in cells treated with contrast agent alone. Consequently, T1-weighted contrast enhancements were observed in cells treated with nanoconjugates but not in cells treated by the contrast agent alone. This type of nanoconjugate with increased retention time, Gd accumulation, and intracellular delivery may find its use in Gd neutron-capture cancer therapy.

Comparison of superparamagnetic and ultrasmall superparamagnetic iron oxide cell labeling for tracking green fluorescent protein gene marker with negative and positive contrast magnetic resonance imaging.

The objectives of this study were to investigate the feasibility of imaging green fluorescent protein (GFP)-expressing cells labeled with iron oxide nanoparticles with the fast low-angle positive contrast steady-state free precession (FLAPS) method and to compare them with the traditional negative contrast technique. The GFP-R3230Ac cell line (GFP cell) was incubated for 24 hours using 20 microg Fe/mL concentration of superparamagnetic iron oxide (SPIO) and ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles. Cell samples were prepared for iron content analysis and cell function evaluation. The labeled cells were imaged using positive contrast with FLAPS imaging, and FLAPS images were compared with negative contrast T2*-weighted images. The results demonstrated that SPIO and USPIO labeling of GFP cells had no effect on cell function or GFP expression. Labeled cells were successfully imaged with both positive and negative contrast magnetic resonance imaging (MRI). The labeled cells were observed as a narrow band of signal enhancement surrounding signal voids in FLAPS images and were visible as signal voids in T2*-weighted images. Positive contrast and negative contrast imaging were both valuable for visualizing labeled GFP cells. MRI of labeled cells with GFP expression holds potential promise for monitoring the temporal and spatial migration of gene markers and cells, thereby enhancing the understanding of cell- and gene-based therapeutic strategies.

Fast low-angle positive contrast steady-state free precession imaging of USPIO-labeled macrophages: theory and in vitro experiment.

The feasibility of imaging macrophages labeled with ultrasmall superparamagnetic iron-oxide nanoparticles (USPIO) with fast low-angle positive contrast steady-state free precession (FLAPS) was investigated through theory and in vitro experiment. Human macrophage cells were labeled with USPIO and imaged at 1.5 T. The metric "visibility," which combines magnitude and spatial extent of positive contrast, was used to evaluate the images. Negative contrast steady-state free precession (SSFP) and gradient-echo (GRE) imaging were also evaluated. Positive contrast was observed for relatively high concentrations of labeled cells for flip angles less than alpha=25 degrees . Theoretical and experimental results indicate that positive visibility (VIS(POS)) was maximized at alpha=10 degrees and 15 degrees. Low flip angle SSFP also provided negative contrast comparable to standard SSFP and GRE imaging. Results suggest that USPIO-labeled macrophages are capable of producing the conditions necessary for positive contrast with FLAPS at clinical field strength (1.5 T) and resolution (0.8x0.8x3 mm(3)).