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.