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      Ultrasmall superparamagnetic iron oxide: characterization of a new class of contrast agents for MR imaging.

      Radiology
      Animals, Capillary Permeability, Cells, Cultured, Contrast Media, Endothelium, Vascular, metabolism, Ferrosoferric Oxide, Iron, diagnostic use, pharmacokinetics, Lymph Nodes, Magnetic Resonance Imaging, Male, Oxides, Particle Size, Rats, Rats, Inbred Strains, Tissue Distribution

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          Abstract

          An ultrasmall superparamagnetic iron oxide (USPIO) preparation was developed that is small enough to migrate across the capillary wall, a prerequisite in the design of targetable particulate pharmaceuticals. Seventy percent of particles were smaller than 10 nm; 26%, smaller than 5 nm. The blood half-life of USPIO in rats was 81 minutes, considerably longer than that of larger superparamagnetic iron oxide preparations such as AMI-25 (6 minutes). Electron microscopy demonstrated that USPIO particles transmigrate the capillary wall by means of vesicular transport and through interendothelial junctions. Twenty-four hours after intravenous administration, 3.6% of the injected dose per gram of tissue was found in lymph nodes, 2.9% per gram in bone marrow, 6.3% per gram in liver, and 7.1% per gram in spleen. The major potential applications for USPIO are as (a) an intravenous contrast agent for the lymphatic system, (b) a bone marrow contrast agent, (c) a long-half-life perfusion agent for brain and heart, and (d) the magnetic moiety in organ-targeted superparamagnetic contrast agents for magnetic resonance imaging.

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