U.S. patents available from 1976 to present.
U.S. patent applications available from 2005 to present.

Hepatocyte specific receptor mediated endocytosis type magnetic resonance imaging contrast agents

Patent 5284646 Issued on February 8, 1994. Estimated Expiration Date: Icon_subject October 3, 2011. Estimated Expiration Date is calculated based on simple USPTO term provisions. It does not account for terminal disclaimers, term adjustments, failure to pay maintenance fees, or other factors which might affect the term of a patent.

Patent References

3325473

3337526

3509126

Magnetic particles for use in separations
Patent #: 4554088
Issued on: 11/19/1985
Inventor: Whitehead ,   et al.

Ferrioxamine-paramagnetic contrast agents for MR imaging, composition, apparatus and use
Patent #: 4637929
Issued on: 01/20/1987
Inventor: Quay

Gadolinium chelates as NMR contrast agents
Patent #: 4639365
Issued on: 01/27/1987
Inventor: Sherry

Diagnostic media
Patent #: 4647447
Issued on: 03/03/1987
Inventor: Gries ,   et al.

Method of magnetic resonance imaging of the liver and spleen
Patent #: 4675173
Issued on: 06/23/1987
Inventor: Widder

Biologically degradable superparamagnetic particles for use as nuclear magnetic resonance imaging agents
Patent #: 4770183
Issued on: 09/13/1988
Inventor: Groman ,   et al.

Use of specific relaxation agents for organs or pathologies for modifying the contrasts in medical imaging by nuclear magnetic resonance
Patent #: 4804529
Issued on: 02/14/1989
Inventor: Bardy ,   et al.

More ...

Inventors

Assignee

Application

No. 771876 filed on 10/03/1991

US Classes:

424/9.322, Polymer containing (e.g., polypeptide, synthetic resin, etc.)252/62.56, Iron-oxygen compound containing424/646, Iron, cobalt, nickel, vanadium, molybdenum, or palladium424/648, Ferrous514/8, Glycoprotein (carbohydrate containing)514/54, Polysaccharide514/57, Cellulose or derivative514/60, Starch or derivative600/420Using detectable material placed in body

Examiners

Primary: Robinson, Allen J.
Assistant: Hollinden, Gary E.

Attorney, Agent or Firm

Foreign Patent References

  • 0184899 EP. 06/20/1986
  • 0186947 EP. 07/20/1986
  • 0210043 EP. 01/20/1987
  • 0186616 EP. 09/20/1990
  • 3443251A1 DE. 11/20/1984
  • 3508000A1 DE. 03/20/1985
  • 85/02772 WO. 07/20/1985
  • 85/04330 WO. 10/20/1985
  • 85/05554 WO. 12/20/1985
  • 86/06605 WO. 11/20/1986

International Classes

G01N 024/08
A61K 037/10

Abstract

A new class of magnetic resonance (MR) contrast agents are described whose in vivo biodistribution is based upon the ability of certain cells to recognize and internalize macromolecules, including the MR contrast agents of the present invention, via a process which substantially involves receptor mediated endocytosis. The RME-type MR contrast agents described herein comprised of biodegradable superparamagnetic metal oxides associated with a variety of macromolecular species, including but not limited to, serum proteins, hormones, asialoglycoproteins, galactose-terminal species, polysaccharides, arabinogalactan, or conjugates of these molecules with other polymeric substances such as a poly(organosilane) and dextran. One of the advantages of these MR contrast agents is that they may be selectively directed to those cells which bear receptors for a particular macromolecule or ligand and are capable of undergoing receptor mediated endocytosis. An MR contrast agent prepared from biodegradable superparamagnetic iron oxide and asialofetuin, or more preferably arabinogalactan, for example, is selectively localized in the hepatocytes of the liver with no significant accumulation in the spleen. An MR experiment which can be carried out shortly after administration to the subject of the contrast agents of the invention can thus provide a method for obtaining an enhanced MR image, as well as valuable information regarding the functional or metabolic state of the organ or tissue under examination. Preparative methods, biodistribution data, and time function MR images are further provided.

Other References

  • Balter, S. "An Introduction to the Physics of Magnetic Resonance Imaging," RadioGraphics 7(2):371-383 (1987)
  • Fullerton, G. D. "Magnetic Resonance Imaging Signal Concepts," RadioGraphics 7(3):579-596 (1987)
  • Runge, V. M. et al. "The Use of Gd DTPA as a Perfusion Agent and Marker of Blood-Brain Barrier Disruption," Magnetic Resonance Imaging 3:45-55 (1985)
  • Renshaw, P. F. et al., "Immunospecific NMR Contrast Agents," Magnetic Resonance Imaging 4:351-357 (1986)
  • Lauffer, R. B. "Paramagnetic Metal Complexes as Water Proton Relaxation Agents for NMR Imaging: Theory and Design," Chem. Rev. 87:901-927 (1987)
  • Helenius, A. et al. "Endosomes," TIBS 8:245-249 (1983)
  • Pastan, I. et al. "Receptor-Mediated Endocytosis: Coated Pits, Receptosomes and the Golgi," TIBS 8:250-254 (1983)
  • Steinman, R. M. et al. "Endocytosis and the Recycling of Plasma Membrane," J. Cell Biol. 96:1-27 (1983)
  • Wileman, T. et al. "Receptor-Mediated Endocytosis," Biochem. J. 232:1-14 (1985)
  • Raff, M. et al. "Self Regulation of Membrane Receptors," Nature 259(25):265-266 (1976)
  • Jacobs, S. et al. "Current Concepts: Cell Receptors in Disease," New Engl. J. Med. 297(25):1383-1386 (1977)
  • Anderson, R. G. W. et al. "Role of the Coated Endocytic Vesicle in the Uptake of Receptor-Bound Low Density Lipoprotein in Human Fibroblasts," Cell 10:351-364 (1977)
  • Murray, G. J. "Mannose 6-Phosphate Receptor-Mediated Uptake of Modified Low Density Lipoprotein Results in Down Regulation of Hydroxymethylglutaryl-CoA Reductase in Normal and Familial Hypercholesterolemic Fibroblasts," J. Biol. Chem. 255(24):11942-11948 (1980)
  • Pastan, I. H. et al. "Journey to the Center of the Cell: Role of the Receptosome," Science 214:504-509 (1981)
  • Sando, G. N. "p-Isothiocyanatophenyl 6-Phospho-଱-D-mannopyranoside Coupled to Albumin. A Model Compound Recognized by the Fibroblast Lysosomal Enzyme Uptake System. 1. Chemical Synthesis and Characterization," Biochem. 19:3850-3855 (1980)
  • Goldstein et al. "The Low-Density Lipoprotein Pathway and Its Relation to Atherosclerosis," Ann. Rev. Biochem 46:897-930 (1977)
  • Harding, C. et al. "Receptor-Mediated Endocytosis of Transferrin and Recycling of the Transferrin Receptor in Rat Reticulocytes," J. Cell Biol. 97:329-339 (1983)
  • Ward, J. H. "The Structure, Function, and Regulation of Transferrin Receptors," Invest. Radiol. 22:74-83 (1987)
  • Larson, S. M. "Factors Determining Tumor Affinity for Gallium-67 Citrate," Radiopharmaceuticals-Structure, Activity Relationships, pp. 167-181 (Spencer, R. P. ed. 1981)
  • Lee, Y. C. et al. "Neoglycoproteins as Probes for Binding and Cellular Uptake of Glycoconjugates," The Glycoconjugates, vol. IV, part B, section 3 (Horowitz, M. I. ed. 1982)
  • Schwartz, A. L. et al. "Characterization of the Asialoglycoprotein Receptor in a Continuous Hepatoma Line," J. Biol. Chem. 256(17):8878-8881 (1981)
  • Stockert, R. J. et al. "Endocytosis of Glycoproteins," The Liver: Biology and Pathobiology, ch. 12 (Arias, I., Popper, H.; Schachter, D.; and Shafritz, D. A., eds.) (1982)
  • Gambhir, K. K. et al. "Insulin Radioreceptor Assay for Human Erythrocytes," Clin. Chem. 23(9):1590-1595 (1977)
  • Beuth, J. et al. "Inhibition of Liver Metastasis in Mice by Blocking Hepatocyte Lectins with Arabinogalactan Infusions and D-galactose," J. Cancer Res. Clin. Oncol. 113:51-55 (1987)
  • Anderson, R. G. W. et al. "Localization of Low Density Lipoprotein Receptors on Plasma Membrane of Normal Human Fibroblasts and Their Absence in Cells from a Familial Hypercholesterolemia Homozygote," PNAS USA 73(7):2434-2438 (1976)
  • Vera, D. R. et al. "Technetium-99m Galactosyl-Neoglycoalbumin: Preparation and Preclinical Studies," J. Nucl. Med. 26(10):1157-1167 (1985)
  • Neutra, M. R. "Intracellular Transport of Transferrin-and Asialoorosomucoid-Colloidal Gold Conjugates to Lysosomes after Receptor-Mediated Endocytosis," J. Histochem. and Cytochem. 33(11):1134-1144 (1985)
  • Handley, D. A. "Colloidal Gold-Low Density Lipoprotein Conjugates as Membrane Receptor Probes," PNAS USA 78(1):368-371 (1981)
  • Ohnisi, S-I, et al. "Role of Endosomes in Endocytic Response of Cells," Studia Biophysica 110:123:126 (1985)
  • Sato, S. B. et al. "A Novel Method for Isolating Specific Endocytic Vesicles Using Very Fine Ferrite Particles Coated with Biological Ligands and the High-Gradient Magnetic Separation Technique," J. Biochem. 100:1481-1492 (1986)
  • Wu, G. et al. "A Hepatocyte-Directed Contrast Agent For Magnetic Resonance Imaging Of Hepatic Tumors," Hepatology 8(5):1253 (1988) (abstract 140)
  • Lee, Y. C. et al. "2-Imino-2-Methoxyethyl 1-Thioglycosides: New Reagents for Attaching Sugars to Proteins," Biochem. 15(18):3956-3963 (1976)
  • Vera, D. R. et al. "Tc-99m Galactosyl-Neoglycoalbumin: In Vitro Characterization of Receptor-Mediated Binding," J. Nucl. Med. 25(7):779-787 (1970)
  • Dubois et al. "Colorimetric Method for Determination of Sugars and Related Substances," Anal. Chem. 28:350-356 (1956)
  • Kitigawa, T. et al. "Enzyme Immunoassay of Blasticidin S with High Sensitivity: A New and Convenient Method for Preparation of Immunogenic (Hapten-Protein) Conjugates," J. Biochem. 92(2):585-590 (1982)
  • Gray, G. R. "The Direct Coupling of Oligosaccharides to Proteins and Derivatized Gels," Arch. of Biochem. and Biophys. 163:426-428 (1974)
  • Spiro, R. G. "Studies on the Monosaccharide Sequence of the Serum Glycoprotein Fetuin," J. Biol. Chem. 237(3):646-652 (1962)
  • Warren, L., "The Thiobarbituric Acid Assay of Sialic Acid," J. Biol. Chem. 234(8):1971-1975 (1959)
  • Stark, D. D. et al. "Magnetic Resonance Imaging of Cavernous Hemangioma of the Liver: Tissue-Specific Characterization," AJR 145:213-220 (1985)
  • Weissieder, R. et al. "Superparamagnetic Iron Oxide: Pharmacokinetics and Toxicity," AJR 152:167-173 (1989)
  • Bolton, A. E. et al. "The Labelling of Proteins to High Specific Radioactivities by Conjugation to a 125 I-Containing Acylating Agent," Biochem. J. 133:529-539 (1973)
  • Greenwood, G. C. et al. "The Preparation of 131 I-Labelled Human Growth Hormone of High Specific Radioactivity," Biochem. J. 89:114-123 (1963)
  • Shirley, C. C. "Regularity within the Molecular Structure of Arabingaloctan from Western Larch (Larix accidentalis)," Carbohydrate Research 64:C1-C2 (1978)
  • Stractan Catalogue published by Champion International Corporation (Oct. 1988
PatentsPlus Images
Enhanced PDF formats
loading...
PatentsPlus: add to cart
PatentsPlus: add to cartSearch-enhanced full patent PDF image
$9.95more info
PatentsPlus: add to cart
PatentsPlus: add to cartIntelligent turbocharged patent PDFs with marked up images
$18.95more info
 
Sign InRegister
Username  
Password   
forgot password?