Iron oxide nanoparticles for use as an MRI contrast agent: pharmacokinetics and metabolism.

The pharmacokinetics and metabolism of a new preparation of superparamagnetic iron oxide nanoparticles were evaluated by 59Fe radiotracer studies and histologic examination of mice liver and spleen tissues (light and transmission electron microscopy). In the first 30 min following IV injection of the product half of the dose injected remains in the blood, the other part being sequestered mainly by the mononuclear phagocyte system (MPS). In the first five days following IV administration of the nanoparticles, early metabolization of the iron oxide cores occurs, revealed by modification of their aspect in the lysosomes of Kupffer cells and macrophages of the splenic red pulp. The incorporation of 59Fe is then observed in RBC of the mice. These results are discussed in relation with the physicochemical properties of this new preparation of nanoparticles, and compared with current pharmacokinetic data concerning injectable particle systems.

[1]  E. Wisse,et al.  An electron microscopic study of the fenestrated endothelial lining of rat liver sinusoids. , 1970, Journal of ultrastructure research.

[2]  P. Couvreur,et al.  New magnetic drug carrier , 1983, The Journal of pharmacy and pharmacology.

[3]  Souhami Rl,et al.  The recovery of hepatic phagocytosis after blockade of Kupffer cells. , 1974 .

[4]  Wayne F. Patton,et al.  Rapid, high-yield purification of cell surface membrane using colloidal magnetite coated with polyvinylamine: sedimentation versus magnetic isolation. , 1985, Biochimica et biophysica acta.

[5]  P. Barthelemy,et al.  Highly stable lanthanide macrocyclic complexes: in search of new contrast agents for NMR imaging. , 1988, International journal of radiation applications and instrumentation. Part B, Nuclear medicine and biology.

[6]  P. Kronick,et al.  Magnetic microspheres prepared by redox polymerization used in a cell separation based on gangliosides. , 1978, Science.

[7]  J. Kemshead,et al.  Removal of malignant cells from bone marrow using magnetic microspheres and monoclonal antibodies. , 1985, Progress in experimental tumor research.

[8]  E. Tomlinson.  Theory and practice of site-specific drug delivery , 1987 .

[9]  L. Josephson,et al.  The effects of iron oxides on proton relaxivity. , 1988, Magnetic resonance imaging.

[10]  T J Brady,et al.  Ferrite particles: a superparamagnetic MR contrast agent for the reticuloendothelial system. , 1987, Radiology.

[11]  J. Wittenberg,et al.  Ferrite particles for bowel contrast in MR imaging: design issues and feasibility studies. , 1987, Radiology.

[12]  R Weissleder,et al.  Superparamagnetic iron oxide: pharmacokinetics and toxicity. , 1989, AJR. American journal of roentgenology.

[13]  A. Ericsson,et al.  Superparamagnetic particles as an MRI contrast agent for the gastrointestinal tract. , 1988, Acta radiologica.

[14]  J C Gore,et al.  Regional differences in rat brain displayed by fast MRI with superparamagnetic contrast agents. , 1988, Magnetic resonance imaging.

[15]  R. Molday,et al.  Immunospecific ferromagnetic iron-dextran reagents for the labeling and magnetic separation of cells. , 1982, Journal of immunological methods.

[16]  R. Weissleder,et al.  MR imaging of splenic metastases: ferrite-enhanced detection in rats. , 1987, AJR. American journal of roentgenology.

[17]  P. Leander,et al.  Magnetic starch microspheres, efficacy and elimination. A new organ-specific contrast agent for magnetic resonance imaging. , 1990, Investigative radiology.

[18]  P. Courtoy,et al.  Plasma protein synthesis in experimental cirrhosis. Morphologic demonstration and functional correlations. , 1981, Laboratory investigation; a journal of technical methods and pathology.

[19]  R. Weissleder,et al.  Ultrasmall superparamagnetic iron oxide: characterization of a new class of contrast agents for MR imaging. , 1990, Radiology.

[20]  R. Perdrisot,et al.  Superparamagnetic iron oxide nanoparticles as a liver MRI contrast agent: contribution of microencapsulation to improved biodistribution. , 1989, Magnetic resonance imaging.

[21]  P F Renshaw,et al.  Ferromagnetic contrast agents: A new approach , 1986, Magnetic resonance in medicine.

[22]  F. Smith,et al.  COLORIMETRIC METHOD FOR DETER-MINATION OF SUGAR AND RELATED SUBSTANCE , 1956 .