Distribution of iron oxide nanoparticles in rat lymph nodes studied using electron energy loss spectroscopy (EELS) and electron spectroscopic imaging(ESI)

Superparamagnetic iron nanoparticles have been developed as contrast agents for magnetic resonance lymphography. The kinetics of uptake of these parti cles has not yet been accurately determined. We have therefore monitored th e distribution of Individual iron particles (ferumoxtran, AMI-227, Sinerem) in rat lymph nodes 1.5, 3, 6, 12, and 24 hours after i.v. injection (two r ats per time point). The ultrastructural distribution of the iron was deter mined by energy-filtered transmission electron microscopy (EFTEM). This met hod allows the identification of elements using element-specific energy-los s electrons. Iron was Identified by the Fe-L-2,L-3 edge (EELS), and Iron ma ps were obtained using Iron-specific electrons for imaging (ESI). The backg round was calculated by simplex optimization (EELS) and by the two-window m ethod (ESI). Ferumoxtran particles were regularly observed at the periphery of the lymph nodes but not In their centers. Isolated iron particles were seen extracellularly within lymph vessels and, 3 hours after injection, as small dots in phagocytic cells. Numerous dense clusters appeared within the cells at later times (6 and 12 hours after injection). These results sugge st that the contrast agent moves rapidly across the capillary wall to the l ymph and is then taken up by phagocytic cells. (C) 2000 Wiley-Liss, Inc.