MR lymphography using iron oxide nanoparticles in rats: Pharmacokinetics in the lymphatic system after intravenous injection

The objective of the study was to quantify the kinetics of the superparamag netic nanoparticle ferumoxtran (AMI 227, Sinerem((R)), Combidex((R))) in th e efferent lymph of the subdiaphragmatic lymph nodes and in various node gr oups of the rat to elucidate the uptake mechanism. The thoracic lymph duct was catheterized in 24 rats after an IV injection of 40 mu mol Fe/kg ferumo xtran. Three rats were studied at several time points between 1.5 and 24 ho urs. At each time point, 0.3 ml of lymph were collected over 45 minutes. Ly mph nodes were differentiated into five groups. The iron concentration in t he samples and in plasma was measured by relaxometry at 0.47 T and atomic a bsorption spectrometry. Cytology was performed on the lymph. High concentra tions of nanoparticles were found in the thoracic lymph soon after injectio n (90 minutes). No particle was found in the lymph cells, indicating that f erumoxtran was extracellular in the lymph fluid. The maximum concentration was reached later in all node groups, at 12 hours, and then plateaued. The transcapillary pathway and subsequent lymph drainage of the particles seem to play a major role in the delivery to the lymph nodes. (C) 2000 Wiley-Lis s, Inc.