MAGNETIC IRON-OXIDE PARTICLES COATED WITH CARBOXYDEXTRAN FOR PARENTERAL ADMINISTRATION AND LIVER CONTRASTING - PRECLINICAL PROFILE OF SH U555A

Rationale and objectives: To evaluate the physical and pharmacological profiles of SH U555A, a suspension of magnetic iron oxide particles t hat is designed to enhance the visualization of liver tumors and metas tases. Material and Methods: Chemical and physical methods were used t o characterize the-size and structure of these magnetic iron oxide par ticles in aqueous solution. The biodistribution and pharmacokinetics o f the particles were studied in mice, rats and dogs. The imaging effic acy of the particles was demonstrated by MR imaging in rat liver tumor s. Results: The SH U555A particles consist of low-molecular-weight car boxydextrancoated iron oxides predominantly of the gamma-Fe2O3 form wi th a hydrodynamic diameter ranging from 57-59 nm and strong T2 relaxiv ity of 164 liters.mmol(-1).s(-1) (water, 0.47 T). In rats the particle s 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 do ses. No major side effects were found. In a rat tumor model the rumor- to-liver contrast was markedly improved after i.v. administration of S H 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. Concl usion: SH U555A is a superparamagnetic MR contrast agent for i.v. admi nistration and has substantial potential for the demarcation of liver tumors.