Determination of liver‐specific r 2 of a highly monodisperse USPIO by 59 Fe iron core‐labeling in mice at 3 T MRI

Accurate determination of tissue concentration of ultrasmall superparamagnetic iron oxide nanoparticles (USPIO) using T 2 * MR relaxometry is still challenging. We present a reliable quantification method for local USPIO amount with the estimation of the liver specific relaxivity r 2 * 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 R 2 * of the liver before and after USPIO injection (∆ R 2 *) was measured and correlated with 59 Fe activity measurements of excised organs by a whole body radioactivity counter (HAMCO) to define the dependency of ∆ R 2 * and 59 FeUSPIO liver concentration and calculate the r 2 * of 59 FeUSPIO for the liver. Ultrastructural analysis of liver uptake was performed by histology and transmission electron microscopy. ∆ R 2 * of the liver revealed a dosage‐dependent accumulation of 59 FeUSPIO with a percentage uptake of 70–88% of the injection dose. Hepatic ∆ R 2 * showed a dose‐dependent linear correlation to 59 FeUSPIO activity measurements ( r = 0.92) and an r 2 * in the liver of 481 ± 74.9 m m −1 s −1 in comparison to an in vitro r 2 * of 60.5 ± 3.3 m m −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 r 2 *. Copyright © 2014 John Wiley & Sons, Ltd. 59 Fe‐labeled USPIO can be used to quantify ∆ R 2 * by generating a standard calibration curve and can be furthermore used to determine tissue‐dependent relaxivities in vivo . This quantification method of signal changes caused by USPIO can serve as a noninvasive tool to monitor disease activity or detect early pathologic tissue alterations.