Differential uptake of ferumoxtran‐10 and ferumoxytol, ultrasmall superparamagnetic iron oxide contrast agents in rabbit: Critical determinants of atherosclerotic plaque labeling

Purpose To compare atherosclerotic plaque uptake of a first (ferumoxtran‐10) and second generation (ferumoxytol) ultrasmall superparamagnetic iron oxide (USPIO) contrast agent with different pharmacokinetic/pharmacodynamic properties. Materials and Methods New Zealand White rabbits maintained on a high cholesterol/fat diet were subjected to balloon injury to the abdominal aorta. Ferumoxtran‐10 or ferumoxytol (500 μmol/kg) was administered at 2, 4, and 8 weeks following injury. In vivo magnetic resonance imaging (MRI) was performed immediately prior to, immediately after, and 6 days post‐contrast administration. Ex vivo MRI, histologic, and inductively coupled plasma‐mass spectrometry (ICP‐MS) iron analyses were performed on the excised vessels. Results The blood pool clearance of ferumoxytol (t½ ≤ 6 hours) was more rapid than that of ferumoxtran‐10 (t½ ≤ 48 hours). Decreased in vivo MRI signal intensity in the abdominal aorta was observed at 2, 4, and 8 weeks following injury with ferumoxtran‐10, but not with ferumoxytol. Consistent with these observations, ex vivo MRI signal intensity was decreased in the ferumoxtran‐10 vessels, and to a lesser degree in the ferumoxytol vs. control vessels (− contrast agent). In contrast, in vitro macrophage phagocytosis of USPIO was four to six fold greater with ferumoxytol than with ferumoxtran‐10. Additionally, the absolute iron content correlated with ex vivo MRI signal intensity in all vessels (r = −0.86, P < 0.0001). Conclusions These data suggest that the exposure period of atherosclerotic plaque to USPIO rather than the kinetics of the USPIO uptake by plaque alone is a critical criterion for experimental design of in vivo studies. J. Magn. Reson. Imaging 2005;21:432–442. © 2005 Wiley‐Liss, Inc.