title: In vitro stability analyses as a model for metabolism of ferromagnetic particles (Clariscan), a contrast agent for magnetic resonance imaging.
abstract: Clariscan is a new contrast agent for magnetic resonance imaging. It is an aqueous suspension of ferromagnetic particles injected for blood pool and liver imaging. Previous experiments showed that particles made of 59Fe were taken up by the mononuclear phagocytic system and then solubilised. The present work aims at explaining a possible mechanism for the dissolution of these ferromagnetic particles in the body. The particles were diluted in 10-mM citrate or 10-mM acetate buffers at pH 4.5, 5.0 and 5.5 and incubated at 37 degrees C for up to 22 days, protected from light. The mixtures were analysed at different times during this incubation period using photon correlation spectroscopy, magnetic relaxation, visible spectroscopy and reactivity of the iron with the chelator, bathophenanthroline disulphonic acid. The data obtained with these techniques showed that the particles were almost completely solubilised within 4-7 days when incubated in 10 mM citrate, pH 4.5. Incubation in 10 mM citrate buffer, pH 5.0 revealed a slower solubilisation of the particles, as the changes observed after 72 h of incubation at pH 5.0 were 43-71% of the changes observed at pH 4.5. Incubation in 10 mM citrate, pH 5.5 revealed an even slower solubilisation of the particles, as the changes observed after 72 h of incubation at pH 5.5 were 12-34% of those observed at pH 4.5. Incubation of the particles in 10 mM acetate at pH 4.5, 5.0 and 5.5, as well as incubation of the particles in water pH adjusted to pH 5.1, resulted in only minor or no solubilisation of the particles. The results indicate that the low pH of endosomes and lysosomes, as well as endogenous iron-complexing substances, may be important for the solubilisation of these ferromagnetic particles following i.v. injection of Clariscan.
authors.affiliation: Research and Development, Nycomed Imaging AS, P.O. Box 4220 Nydalen, N-0401 Oslo, Norway. tore.skotland@no.nycomed-amersham.com
authors.forename: Tore
authors.initials: T
authors.lastname: Skotland
authors.forename: Per Christian
authors.initials: PC
authors.lastname: Sontum
authors.forename: Inger
authors.initials: I
authors.lastname: Oulie
mesh_terms: D003287:Contrast Media / Q000032:analysis* / Q000378:metabolism; D003911:Dextrans; D004355:Drug Stability; D005290:Ferric Compounds / Q000032:analysis* / Q000378:metabolism; D052203:Ferrosoferric Oxide; D006863:Hydrogen-Ion Concentration; D007501:Iron / Q000032:analysis* / Q000378:metabolism; D007502:Iron Chelating Agents / Q000737:chemistry; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles; D008863:Microspheres; D008954:Models, Biological; D010087:Oxides / Q000032:analysis* / Q000378:metabolism; D017785:Photons; D012542:Scattering, Radiation; D013056:Spectrophotometry, Ultraviolet
chemical_list: D003287:Contrast Media; D003911:Dextrans; D005290:Ferric Compounds; D007502:Iron Chelating Agents; D058185:Magnetite Nanoparticles; D010087:Oxides; C097921:ferumoxtran-10; C000499:ferric oxide; D007501:Iron; D052203:Ferrosoferric Oxide