Physical and chemical properties of superparamagnetic iron oxide MR contrast agents: ferumoxides, ferumoxtran, ferumoxsil.

The bulk physiochemical properties of the active ingredients in three AMI colloidal, superparamagnetic iron oxide (SPIO), MR contrast agents are described. Ferrous content and X-Ray diffraction (XRD) of the colloids are consistent with nonstoichiometric magnetite phases in all three active ingredients. No separate maghemite (gamma-Fe2O3) phases were detected by XRD. XRD line-broadening determinations of representative samples of ferumoxides (dextran coated), Ferumoxtran (dextran covered), and ferumoxsil (siloxane coated) yielded mean crystal diameters (volume weighted distribution) of 4.8-5.6, 5.8-6.2, and 7.9-8.8 nm, respectively. Transmission electron microscopy (TEM) showed that the crystal sizes were lognormally distributed with respective mean crystal diameters (number weighted distribution) of 4.3-4.8, 4.3-4.9, and 8.0-9.5 nm, respectively. Consistent with their small crystal sizes, the three SPIO colloids are superparamagnetic with no remanence after saturation at high applied fields (< 1 T), and showed characteristic relaxed Mössbauer spectra. The Mössbauer spectra of ferumoxides and Ferumoxtran were consistent with the presence of superparamagnetic relaxation above a blocking temperature of approximately 60 K. Due to the larger crystal sizes of ferumoxsil, its Mössbauer spectra showed the presence of rapid collective magnetic excitations on the Mössbauer time scale (approximately 1-10 ns). All three colloids showed high MR relaxivities. TEM of the SPIO colloids showed that ferumoxides and ferumoxsil are composed of aggregates of nonstoichiometric magnetite crystals, while Ferumoxtran consists of single crystals of nonstoichiometric magnetite. Dynamic light scattering (PCS) measurements showed that Ferumoxtran particles have average hydrodynamic diameters of approximately 21 nm (number weighted distribution) or 30 nm (volume weighted distribution). The data indicate that Ferumoxtran crystals are coated with an 8-12 nm layer of dextran T-10. Ferumoxides aggregates have average particle sizes of approximately 35 nm (number average distribution; TEM and PCS), or approximately 50 nm (volume weighted distribution; PCS). Mean sizes of ferumoxsil aggregates are approximately 300 nm (intensity weighted distribution). A discussion of the various particle size distributions is presented.