Phase I clinical evaluation of citrate-coated monocrystalline very small superparamagnetic iron oxide particles as a new contrast medium for magnetic resonance imaging

RATIONALE AND OBJECTIVES: To evaluate the safety and pharmacokinetics of a newly developed MR contrast medium consisting of very small superparamagnetic iron oxide particles (VSOP) coated with citrate (VSOP-C184) in a clinical phase I trial. METHODS: A total of 18 healthy subjects received either VSOP-C184 (core diameter: 4 nm; total diameter: 7 +/- 0.15 nm; relaxivities in water at 0.47 T (T1) 18.7 and (T2) 30 L/(mmol*seconds)) at doses of 0.015, 0.045, or 0.075 mmol Fe/kg (n = 5 per dose) or placebo (n = 1 per dose) as intravenous injections. Physical status and vital parameters were recorded, blood samples were collected for clinical chemistry and relaxometry (0.94 T), and urinalyses were performed before and for up to 2 weeks after administration. RESULTS: No serious adverse events occurred. The most pronounced adverse events occurred in 2 subjects of the highest dose group 45-50 minutes after injection. These were a drop in blood pressure and a drop in oxygen saturation, which were considered to be possibly drug-related and rapidly resolved without medication. Otherwise, no relevant changes in vital and laboratory parameters were observed. The parameters of iron metabolism exhibited short-term, dose-related changes. The injection of VSOP-C184 decreased T1 relaxation time of blood below 100 milliseconds for 18 minutes after a dose of 0.045 mmol [corrected] Fe/kg and for 60 minutes after 0.075 mmol [corrected] Fe/kg. CONCLUSIONS: The favorable data on the safety, tolerability, and efficacy of VSOP-C184 justify further clinical phase II and III trials as a contrast medium for MRI.