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.