The pharmacokinetics of the lymphotropic nanoparticle MRI contrast agent ferumoxtran-10.
Ferumoxtran-10 is an ultrasmall superparamagnetic biodegradable iron oxide which serves as a MRI contrast agent in the differentiation of metastatic and non-metastatic lymph nodes in primary malignancies and imaging of phagocyte-associated disease processes. Ferumoxtran-10 is supplied as a lyophilized powder containing 210 mg of iron, 631 mg of dextran, and 27 mg of sodium citrate. The iron oxide core determines the magnetic properties of ferumoxtran-10, primarily its effects on the MR relaxation times, T1, T2, and T2*. Attachment of dextran prolongs the circulatory time of the nanoparticles. The intended human dose of ferumoxtran-10 is 2.6 mg Fe/kg. Reconstituted and diluted with physiological saline it is administered intravenously by means of a slow drip infusion. After initial vascular distribution of the particles, they are slowly phagocytosed by the reticuloendothelial system cells of the spleen, lymph nodes, bone marrow, and liver. When ferumoxtran-10 is present in phagocytic cells the iron oxide causes local magnetic field inhomogeneities which lead to increases in proton relaxation rates, resulting in signal loss on mid-T1/T2 or heavily T2-weighted MR images. Stored in lysosomes the particles are ultimately degraded: the iron enters the normal body iron metabolism cycle and dextran is eliminated mainly via the kidney.
Islam
Tina
T
Center for Molecular Imaging Research, Charlestown, MA, USA. islam.tina@mgh.harvard.edu
Wolf
Gerald
G
D000818:Animals; D003287:Contrast Media / Q000493:pharmacokinetics*; D003911:Dextrans; D052203:Ferrosoferric Oxide; D006801:Humans; D007501:Iron / Q000493:pharmacokinetics*; D008198:Lymph Nodes / Q000473:pathology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008280:Magnetics; D058185:Magnetite Nanoparticles; D010087:Oxides / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D003287:Contrast Media; D003911:Dextrans; D058185:Magnetite Nanoparticles; D010087:Oxides; C097921:ferumoxtran-10; D007501:Iron; D052203:Ferrosoferric Oxide