Preclinical safety and pharmacokinetic profile of ferumoxtran-10, an ultrasmall superparamagnetic iron oxide magnetic resonance contrast agent.

OBJECTIVES: This report presents an overview of preclinical data available on ferumoxtran-10, an ultrasmall superparamagnetic iron oxide nanoparticular contrast agent proposed for lymph node magnetic resonance imaging. MATERIALS AND METHODS: Pharmacokinetic, safety pharmacology, single- and repeat-dose toxicity, reproduction toxicity, and genotoxicity studies were performed with ferumoxtran-10 given intravenously (bolus injection) in mice, rats, rabbits, dogs, and monkeys. RESULTS: Ferumoxtran-10 was taken up by macrophages, mostly in liver, spleen, and lymph nodes, within 24 hours after bolus injection and underwent progressive metabolism. Toxicity was observed only at very high exposure levels and mainly was linked to a massive iron load after repeated injections. Ferumoxtran-10 was not mutagenic but was teratogenic in rats and rabbits. DISCUSSION: The preclinical pharmacokinetic and safety profile of ferumoxtran-10 appears to be satisfactory in view of its proposed use as a single-dose diagnostic agent in human for MR imaging of lymph nodes.

First-pass contrast-enhanced magnetic resonance angiography in humans using ferumoxytol, a novel ultrasmall superparamagnetic iron oxide (USPIO)-based blood pool agent.

PURPOSE: To evaluate the feasibility of first-pass contrast-enhanced magnetic resonance angiography (MRA) using ferumoxytol in humans. MATERIALS AND METHODS: First-pass and equilibrium phase MRA were performed using ferumoxytol in one healthy volunteer and 11 patients with a fast three-dimensional spoiled gradient recalled (SPGR) pulse sequence. The examined vessels included carotid arteries, thoracic aorta, abdominal aorta, and peripheral arteries. A dose of either 71.6 micromol Fe/kg (n = 9), or 35.8 micromol Fe/kg (n = 3) was used. Based on a phantom study, the agent with initial concentration of 537.2 micromol Fe/mL was diluted by either four-fold (134.3 micromol Fe/mL) or eight-fold (67.1 micromol Fe/mL) for first-pass MRA. RESULTS: All subjects completed their studies without adverse events. First-pass MRA showed selective arterial enhancement, with both arterial and venous enhancement on delayed acquisitions. Selective venous enhancement could be obtained by subtraction of arterial phase images from equilibrium phase images. The findings in ferumoxytol MRA were consistent with the results of original vascular tests. CONCLUSION: Our preliminary experience supports the feasibility of first-pass MRA with ferumoxytol. Satisfactory arterial enhancement during first-pass imaging is obtained with injection of diluted contrast agent. With ferumoxytol, arteries and veins can be selectively depicted in a single exam.