Biodistribution of ultrasmall iron oxide particles in the rat liver

Ferumoxtran, an ultrasmall superparamagnetic Iron oxide particle, can be lo cated in several tissue compartments in the liver, namely the extracellular space (blood and interstitium), reticuloendothelial cells, and possibly he patocytes. To better understand the compartmental distribution of ferumoxtr an in the liver, we performed a longitudinal study in the rat using microsc opy and magnetic resonance imaging. At light microscopy, no substantial cel lular uptake of ferumoxtran was observed before one hour after injection. W ith a dose of 15 mu mol Fe/kg, the number of ferumoxtran particles in the r eticuloendothelial cells peaked between one and four hours and with a 150 m u mol Fe/kg dose, it peaked between eight and 24 hours. Within hepatocytes, only sparse particles were observed with electron microscopy, at a dose of 150 mu mol Fe/kg. Imaging performed up until one hour after ferumoxtran In jection showed a significant increase in liver signal intensity on T1-weigh ted images. These results suggest that ferumoxtran mainly acts as an extrac ellular agent for at least one hour in the rat and that reticuloendothelial accumulation peaks at later time points. Substantial uptake within hepatoc ytes did not occur. (C) 2001 Wiley-Liss, Inc.