Fe3O4/MnO hybrid nanocrystals as a dual contrast agent for both T1- and T2-weighted liver MRI

To investigate whether it is possible to develop a dual magnetic resonance (MR) contrast agent, Fe3O4/MnO hybrid nanocrystals were modified to integrate the T1 and T2 contrast-enhancing abilities of each compound, and their characteristics as MR contrast agents were investigated. In vitro and in vivo investigations revealed that the Fe3O4/MnO dumbbell-shaped nanocrystal exerted a negative T2 contrast effect in its intact form and also gave rise to a positive contrast effect in T1-weighted MR imaging by releasing Mn2+ ions in a low pH environment. This induced organ-specific contrast enhancement for both T1- and T2-weighted in vivo MR imaging. The usefulness of the Fe3O4/MnO hybrid nanocrystals as dual contrast agents was evaluated by in vivo MR imaging of an orthotopic xenograft model of human hepatocellular carcinoma (HCC). After injection of the Fe3O4/MnO hybrid nanocrystals, dual contrast-enhanced MR images that synergistically combined the T2 and T1 contrast effects from the Fe3O4 grain and released Mn2+ ions were obtained by a single acquisition of MR imaging. This facilitated the detection of HCC with a high degree of conspicuity that could not be achieved with any single contrast agent.