Determination of liver-specific r 2 * of a highly monodisperse USPIO by 59 Fe iron core-labeling

Accurate determination of tissue concentration of ultrasmall superparamagnetic iron oxide nanoparticles (USPIO) using T2* MR relaxometry is still challenging. We present a reliable quantification method for local USPIO amount with the estimation of the liver specific relaxivity r2* using monodisperse 59 Fe-core-labeled USPIO ( 59 FeUSPIO). Dynamic and relaxometric in vivo characteristics of unlabeled monodisperse USPIO were determined in MRI at 3 T. The in vivo MR studies were performed for liver tissue with 59 FeUSPIO using iron dosages of 9 (n=3), 18 (n=2) and 27 (n=3) μmol Fe kg � 1 body weight. The R2* of the liver before and after USPIO injection (ΔR2*) was measured and correlated with 59 Fe activity measurements of excised organs by a whole body radioactivity counter (HAMCO) to define the dependency of ΔR2* and 59 FeUSPIO liver concentration and calculate the r2 *o f 59 FeUSPIO for the liver. Ultrastructural analysis of liver uptake was performed by histology and transmission electron microscopy. ΔR2* of the liver revealed a dosage-dependent accumulation of 59 FeUSPIO with a percentage uptake of 70–88% of the injection dose. Hepatic ΔR2* showed a dose-dependent linear correlation to 59 FeUSPIO activity measurements (r=0.92) and an r2* in the liver of 481±74.9 mM � 1 s � 1 in comparison to an in vitro r2* of 60.5±3.3 mM � 1 s � 1 . Our results indicate that core-labeled 59 FeUSPIO can be used to quantify the local amount of USPIO and to estimate the liver-specific relaxivity r2*. Copyright © 2014 John Wiley & Sons, Ltd. Additional supporting information may be found in the online version of this article at the publisher’s web site.