Preclinical evaluation of severely defective manganese-based nanocrystal as a liver-specific contrast media for MR imaging: comparison with Gd-EOB-DTPA and MnDPDP

Abstract Manganese-based (chemically formulated of KMnF ₃ ) nanocrystal was evaluated as a liver-specific contrast agent for MR imaging and its imaging performance was also compared with those of two commercial hepatobiliary contrast media (Gd-EOB-DTPA and MnDPDP). KMnF ₃ nanocrystal was post-treated using a plasma technique to cause severe defects, leading to appropriate water dispersibility and high relaxivity. Severely defective KMnF ₃ nanocrystal (SD-KMnF ₃ ) has characteristic high tolerance, as evidenced by cytotoxicity on the macrophage cell, and acute and subchronic toxicity on the healthy mouse. SD-KMnF ₃ showed better hepatic MR imaging as the T ₁ relaxation time of the liver decreased to only 17% of the control group, compared to 22% of the control group for Gd-EOB-DTPA ( P < 0.01) and 42% of the control group for MnDPDP ( P < 0.001). As applied to MR imaging of the allograft orthotopic model of liver cancer, statistical studies demonstrated that SD-KMnF ₃ significantly improved the tumor’s contrast-to-noise ratio, compared with Gd-EOB-DTPA ( P < 0.01) and MnDPDP ( P < 0.01) by spin-echo pulse sequence, and even better performance ( P < 0.001) by gradient-echo sequence. Our findings indicate that SD-KMnF ₃ could serve as a hepatic contrast agent for imaging liver cancer such as hepatocarcinoma or metastatic lesions.