Magnetic resonance imaging (MRI) can detect atherosclerotic lesions containing accumulations of ultrasmall superparamagnetic
iron oxides (
USPIO). Positing that improved
USPIO with a higher affinity for
atherosclerotic plaques would yield better plaque images, we performed MRI and histologic studies to compare the uptake of
dextran- and
mannan-
dextran-coated
USPIO (D-
USPIO and DM-
USPIO, respectively) by the atherosclerotic walls of rabbits. We intravenously injected atherosclerotic rabbits with DM-
USPIO (n = 5) or D-
USPIO (n = 5). Two rabbits were the controls. The doses delivered were 0.08 (dose 1) (n = 1), 0.4 (dose 2) (n = 1), or 0.8 (dose 3) (n = 3) mmol
iron/Kg. The dose 3 rabbits underwent in vivo contrast-enhanced magnetic resonance angiography (MRA) before and 5 days after
USPIO administration. Afterwards, all animals were euthanized, the aortae were removed and subjected to in vitro MRI study. The signal-to-noise ratio (SNR) of the aortic wall in the same region of interest (ROI) was calculated in both in vivo and in vitro studies. Histological assessment through measurement of
iron-positive regions in
Prussian blue-stained specimens showed that
iron-positive regions were significantly larger in rabbits injected with DM- rather than D-
USPIO (P < 0.05) for all doses. In vivo MRA showed that the SNR-reducing effect of DM- was greater than that of D-
USPIO (P < 0.05). With in vitro MRI scans, SNR was significantly lower in rabbits treated with dose 2 of DM-
USPIO compared with D-
USPIO treatment (P < 0.05), and it tended to be lower at dose 3 (P < 0.1). In conclusion, we suggest that DM-
USPIO is superior to D-
USPIO for the study of atherosclerotic lesions in rabbits.