Claims for Patent: 4,770,183

Summary for Patent: 4,770,183

Title:	Biologically degradable superparamagnetic particles for use as nuclear magnetic resonance imaging agents
Abstract:	This invention relates to an improved method for obtaining the in vivo MNR image of an organ or tissue of an animal or human subject. More specifically, this invention relates to the use of small (about 10 to about 5,000 angstroms in diameter) biodegradable superparamagnetic metal oxide particles for use as imaging agents. The particles, which may be uncoated or surrounded by a stable polymeric coating, can be mixed with a physiologically acceptable medium to form a uniform dispersoid which can be administered to the subject by a variety of routes. Once administered, the particles collect in the target organ or tissue where they will remain for a time sufficiently long for an image to be obtained, but are ultimately metabolized or cleared within about 7 days.
Inventor(s):	Groman; Ernest V. (Brookline, MA), Josephson; Lee (Arlington, MA)
Assignee:	Advanced Magnetics Incorporated (Cambridge, MA)
Application Number:	06/882,044
Patent Claims:	1. An improved method for obtaining an in vivo NMR image or an organ or tissue of an animal or human subject, wherein the improvement comprises administering to such a subject as a contrast agent to enhance such NMR image an effective amount of a dispersoid which comprises uncoated, biodegradable superparamagnetic metal oxide particles dispersed in a physiologically acceptable carrier, an individual particle (i) comprising one or more biodegradable metal oxide crystals, each crystal about 10 to about 500 angstroms in diameter; (ii) having an overall means diameter of about 10 angstroms to about 5000 angstroms as measured on a Coulter particle size analyzer; and (iii) further characterized as having a retention time in said organ or tissue sufficiently long to permit an image to be obtained and being ultimately biodegraded in said organ or tissue within a period of about 7 days. 2. An improved method for obtaining an in vivo NMR image of an organ or tissue of an animal or human subject, wherein the improvememt comprises administering to such a subject as a contrast agent to enhance such NMR image an effective amount of a dispersoid which comprises coated, biodegradable superparamagnetic metal oxide particles dispersed in a physiologically acceptable carrier, an individual particle (i) comprising a superparamagnetic metal oxide core generally surrounded by a biodegradable polymeric coat, each core comprising one or more biodegradable metal oxide crystals, each crystal about 10 to about 500 angstroms in diameter; (ii) having an overll mean diameter, inclusive of the polymeric coat, of about 10 to about 5000 angstroms as measured on a Coulter particle size analyzer; an (iii) further characterized as having a retention time in said organ or tissue sufficiently long to permit an image to be obtained and being ultimately biodegraded in said organ or tissue within a period of about 7 days. 3. The method of claim 1 or 2 wherein the superparamagetic metal oxide particle is an iron oxide particle (i) comprising crystals of about 50 to about 500 angstroms in diameter; (ii) having a surface area greater than about 75 m.sup.2 /gram; (iii) having a magnetic saturation between about 5 and about 50 EMU/gram of iron oxide; and (iv) possessing a magnetic squareness of less than 0.1. 4. The method of claim 2 wherein the polymeric coat is selected from the group consisting of carbohydrates, proteins, and composites thereof. 5. The method of claim 2 wherein the polymeric coat consists of albumin. 6. The method of claim 5 wherein the albumin is selected from the group consisting of human serum albumin and bovine serum albumin. 7. The method of claim 2 wherein the polymeric coat consists of dextran having a molecular weight between 5,000 and 250,000 daltons. 8. The method of claim 7 wherein the dextran is selected from the group consisting of dextran of 9,000 MW, dextran of 17,900 MW, dextran of 35,600 MW, dextran of 71,000 MW and dextran of 249,000 MW. 9. The method of claim 1 or 2 wherein said dispersoid is administered to the subject by intravascular injection. 10. The method of claim 1 or 2 wherein said dispersoid is administered to the subject by a method selected from the group consisting of oral administration, intubation, and by enema. 11. The method of claim 9 wherein the physiologically acceptable carrier is selected from the group consisting of normal saline and distilled water. 12. The method of claim 10 wherein said physiologically acceptable carrier is distilled water. 13. The method of claim 1 or 2 wherein the superparamagnetic metal oxide particles are administered at a dosage of up to about 250 mg per Kilogram of body weight of the subject. 14. The method of claim 1 or 2 wherein the organ or tissue imaged is part of the reticuloendothelial system. 15. The method of claim 14 wherein the organ imaged is a liver. 16. The method of claim 14 wherein the organ imaged is a spleen. 17. The method of claim 14 wherein the tissue imaged is bone marrow. 18. The method of claim 14 wherein the organ or tissue imaged is lymph or lymph nodes. 19. The method of claim 1 or 2 wherein the tissue imaged is neural tissue. 20. The method of claim 1 or 2 wherein the organ imaged is a lung. 21. The method of claim 1 or 2 wherein the organ or tissue imaged is part of the gastrointestinal tract. 22. The method of claim 21 wherein the organ imaged is an esophagus. 23. The method of claim 21 wherein the organ imaged is a stomach. 24. The method of claim 21 wherein the organ imaged is a small intestine. 25. The method of claim 21 wherein the organ imaged is a large intestine.