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


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.


CONCLUSIONS
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.
Bourrinet
Philippe
P
Guerbet, Roissy CDG Cedex, France. philippe.bourrinet@guerbet-group.com
Bengele
Howard H
HH
Bonnemain
Bruno
B
Dencausse
Anne
A
Idee
Jean-Marc
JM
Jacobs
Paula M
PM
Lewis
Jerome M
JM
D000818:Animals; D003911:Dextrans; D004285:Dogs; D052203:Ferrosoferric Oxide; D000882:Haplorhini; D007501:Iron / Q000493:pharmacokinetics* / Q000633:toxicity*; D008198:Lymph Nodes; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles; D051379:Mice; D010087:Oxides / Q000493:pharmacokinetics* / Q000633:toxicity*; D011817:Rabbits; D051381:Rats
D003911:Dextrans; D058185:Magnetite Nanoparticles; D010087:Oxides; C097921:ferumoxtran-10; D007501:Iron; D052203:Ferrosoferric Oxide