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

Abstract 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 ( r 1 = 8.3 mM −1 s −1 ) is larger than that of clinically used T 1 ‐positive agent Gd‐DTPA ( r 1 = 4.8 mM −1 s −1 ), and three times that of commercial contrast agent SHU‐555C ( r 1 = 2.9 mM −1 s −1 ). The transversal relaxivity ( r 2 = 35.1 mM −1 s −1 ) is six times that of Gd‐DTPA ( r 2 = 5.3 mM −1 s −1 ), half of SHU‐555C ( r 2 = 69 mM −1 s −1 ). The in vivo results show that the liver signal from T 1 ‐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 T 2 ‐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.