Functionalizable silica-based micron-sized iron oxide particles for cellular magnetic resonance imaging.

Cellular therapies require methods for noninvasive visualization of transplanted cells. Micron-sized iron oxide particles (MPIOs) generate a strong contrast in magnetic resonance imaging (MRI) and are therefore ideally suited as an intracellular contrast agent to image cells under clinical conditions. However, MPIOs were previously not applicable for clinical use. Here, we present the development and evaluation of silica-based micron-sized iron oxide particles (sMPIOs) with a functionalizable particle surface. Particles with magnetite content of >40% were composed using the sol-gel process. The particle surfaces were covered with COOH groups. Fluorescein, poly-L-lysine (PLL), and streptavidin (SA) were covalently attached. Monodisperse sMPIOs had an average size of 1.18 µm and an iron content of about 1.0 pg Fe/particle. Particle uptake, toxicity, and imaging studies were performed using HuH7 cells and human and rat hepatocytes. sMPIOs enabled rapid cellular labeling within 4 h of incubation; PLL-modified particles had the highest uptake. In T2*-weighted 3.0 T MRI, the detection threshold in agarose was 1,000 labeled cells, whereas in T1-weighted LAVA sequences, at least 10,000 cells were necessary to induce sufficient contrast. Labeling was stable and had no adverse effects on labeled cells. Silica is a biocompatible material that has been approved for clinical use. sMPIOs could therefore be suitable for future clinical applications in cellular MRI, especially in settings that require strong cellular contrast. Moreover, the particle surface provides the opportunity to create multifunctional particles for targeted delivery and diagnostics.

Feasibility of fast dynamic MRI for noninvasive monitoring during ectopic liver cell transplantation to the spleen in a porcine model.

OBJECTIVE: Liver cell transplantation is a promising approach for the treatment of metabolic liver disorders. However, a method for noninvasive monitoring during liver cell transplantation is not available clinically. The aim of this study was to investigate the feasibility of fast dynamic MRI monitoring during liver cell infusion to the spleen, which is considered an ectopic implantation site for liver cell transplantation. MATERIALS AND METHODS: Porcine liver cells were labeled with micron-sized iron oxide particles and infused to the spleens of pigs (n = 5) via the lineal artery. MRI was performed using a 3-T MR scanner. Initially, T1- and T2-weighted pulse sequences were tested. Thereafter, fast dynamic MRI was performed during cell infusion. MR findings were verified by immunohistological examinations. RESULTS: Images from static MRI (TR/TE, 2500/105.2) showed significantly lower signal intensity and signal-to-noise ratio after cell infusion compared with pretransplant images. T2-weighted fast dynamic MRI enabled visualization of signal decrease of the spleen during cell infusion. When cells were infused systemically, no signal changes in the spleen were observed. CONCLUSION: This study shows that fast dynamic MRI can enable noninvasive monitoring during liver cell transplantation to the spleen. This approach could be useful for preclinical studies and for quality control of clinical liver cell transplantation.