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

作者：Raabe Nina^*; Forberich Evelyn; Freund Barbara; Bruns Oliver T; Heine Markus; Kaul Michael G; Tromsdorf Ulrich; Herich Lena; Nielsen Peter; Reimer Rudolph; Hohenberg Heinrich; Weller Horst; Schumacher U; Adam Gerhard; Ittrich Harald

来源：Contrast Media and Molecular Imaging, 2015, 10(2): 153-162.

DOI：10.1002/cmmi.1612

• USPIO
• relaxometry
• 3T MRI
• quantification
• animal study

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 Fe-59-core-labeled USPIO ((FeUSPIO)-Fe-59). 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 (FeUSPIO)-Fe-59 using iron dosages of 9 (n=3), 18 (n=2) and 27 (n=3) mu mol Fe kg(-1) body weight. The R-2* of the liver before and after USPIO injection (R-2*) was measured and correlated with Fe-59 activity measurements of excised organs by a whole body radioactivity counter (HAMCO) to define the dependency of R-2* and (FeUSPIO)-Fe-59 liver concentration and calculate the r(2)* of (FeUSPIO)-Fe-59 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 (FeUSPIO)-Fe-59 with a percentage uptake of 70-88% of the injection dose. Hepatic R-2* showed a dose-dependent linear correlation to (FeUSPIO)-Fe-59 activity measurements (r=0.92) and an r(2)* in the liver of 48174.9 mm(-1) s(-1) in comparison to an in vitro r(2)* of 60.5 +/- 3.3 mm(-1) s(-1). Our results indicate that core-labeled (FeUSPIO)-Fe-59 can be used to quantify the local amount of USPIO and to estimate the liver-specific relaxivity r(2)*. Copyright (c) 2014 John Wiley & Sons, Ltd.
Fe-59-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.

• 出版日期2015-4