Monomer-coated very small superparamagnetic iron oxide particles as contrast medium for magnetic resonance imaging - Preclinical in vivo characterization

RATIONALE AND OBJECTIVES. Preclinical in-vivo characterization of a newly developed MR contrast medium consisting of very small superparamagnetic iron oxide particles (VSOP) coated with citrate (VSOP-C184). METHODS. VSOP-C184 (core diameter: 4 nm; total diameter: 8.6 nm; relaxivities in water at 0.94 T (T1) 20.1 and (T2) 37.1 I/[mmol*sec]) was investigated to determine its pharmacokinetics, efficacy, acute single dose toxicity, repeated dose toxicity, and genotoxicity. RESULTS. The plasma elimination half-life at 0.045 mmol Fe/kg was 21.3 +/- 5.5 minutes in rats and 36.1 +/- 4.2 minutes in pigs, resulting in a T1-relaxation time of plasma of < 100 milliseconds for 30 minutes in pigs. The particles are mainly cleared via the phagocytosing system of the liver. MR angiography at a dose of 0.045 mmol Fe/kg shows an excellent depiction of the thoracic and abdominal vasculature in rats and of the coronary arteries in pigs. The LD50 in mice is > 17.9 mmol Fe/kg. A good tolerance and safety profile was found. CONCLUSIONS. The experiments indicate, that VSOP-C184 may be a well tolerated and safe contrast medium for MR imaging that can be effectively used for MR angiography including visualization of the coronary arteries.