Magnetic iron oxide particles coated with carboxydextran for parenteral administration and liver contrasting - Pre-clinical profile of SH U555A

Rationale and objectives: To evaluate the physical and pharmacological profiles of SH U555A, a suspension of magnetic iron oxide particles that is designed to enhance the visualization of liver tumors and metastases. Material and Methods: Chemical and physical methods were used to characterize the-size and structure of these magnetic iron oxide particles in aqueous solution. The biodistribution and pharmacokinetics of the particles were studied in mice, rats and dogs. The imaging efficacy of the particles was demonstrated by MR imaging in rat liver tumors. Results: The SH U555A particles consist of low-molecular-weight carboxydextrancoated iron oxides predominantly of the gamma-Fe2O3 form with a hydrodynamic diameter ranging from 57-59 nm and strong T2 relaxivity of 164 liters.mmol(-1).s(-1) (water, 0.47 T). In rats the particles exhibited a dose-dependent half-life of between 2 and 3 days in the liver at a dose of 20 mu mol Fe/kg and a shorter half-life at lower doses. No major side effects were found. In a rat tumor model the rumor-to-liver contrast was markedly improved after i.v. administration of SH U555A, At a dose of 14 mu mol Fe/kg the half-maximal contrast-effect was obtained even in nonoptimized T1-weighted spin-echo images. Conclusion: SH U555A is a superparamagnetic MR contrast agent for i.v. administration and has substantial potential for the demarcation of liver tumors.