  We report on the synthesis, characterization, stability and pharmacokinetics
of novel iron based contrast agents for magnetic resonance imaging (MRI).
Statistical copolymers combining multiple phosphonic acid groups and
poly(ethylene glycol) (PEG) were synthesized and used as coating agents for 10
nm iron oxide nanocrystals. In vitro, protein corona and stability assays show
that phosphonic acid PEG copolymers outperform all other coating types
examined, including low molecular weight anionic ligands and polymers. In vivo,
the particle pharmacokinetics is investigated by monitoring the MRI signal
intensity from mouse liver, spleen and arteries as a function of the time,
between one minute and seven days after injection. Iron oxide particles coated
with multi-phosphonic acid PEG polymers are shown to have a blood circulation
lifetime of 250 minutes, i.e. 10 to 50 times greater than that of recently
published PEGylated probes and benchmarks. The clearance from the liver takes
in average 2 to 3 days and is independent of the core size, coating and
particle stability. By comparing identical core particles with different
coatings, we are able to determine the optimum conditions for stealth MRI
probes.
