Ultrasmall Water-Soluble and Biocompatible Magnetic Iron Oxide Nanoparticles as Positive and Negative Dual Contrast Agents

Monodispersed water-soluble and biocompatible ultrasmall magnetic iron oxide nanoparticles (UMIONs, D = 3.3 +/- 0.5 nm) generated from a high-temperature coprecipitation route are successfully used as efficient positive and negative dual contrast agents of magnetic resonance imaging (MRI). Their longitudinal relaxivity at 4.7 T (r1 = 8.3 mM-1 s-1) is larger than that of clinically used T1-positive agent Gd-DTPA (r1 = 4.8 mM-1 s-1), and three times that of commercial contrast agent SHU-555C (r1 = 2.9 mM-1 s-1). The transversal relaxivity (r2 = 35.1 mM-1 s-1) is six times that of Gd-DTPA (r2 = 5.3 mM-1 s-1), half of SHU-555C (r2 = 69 mM-1 s-1). The in vivo results show that the liver signal from T1-weighted MRI is positively enhanced 26%, and then negatively decreased 20% after injection of the iron oxide nanoparticles, which is stronger than those obtained from Gd-DTPA (<10%) using the same dosage. The kidney signal is positively enhanced up to 35%, similar to that obtained from Gd-DTPA. Under T2-weighted conditions, the liver signal is negatively enhanced ?70%, which is significantly higher than that from Gd-DTPA (?6%). These results demonstrate the great potential of the UMIONs in dual contrast agents, especially as an alternative to Gd-based positive contrast agents, which have risks of inducing side effects in patients.