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Details for Patent: 5,141,739

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Details for Patent: 5,141,739

Title: Delivery of x-ray contrast agents using receptor mediated endocytosis
Abstract:The invention provides a method of targeting an x-ray contrast agent to a specific population of cells or organ. Targeting may be accomplished by forming a complex of a radiopaque label with a saccharide capable of interacting with a cell receptor. The resulting complex may then be internalized into the specific population of cells or organ by receptor mediated endocytosis. In one embodiment of the invention, the radiopaque label may include a compound containing iodine and the saccharide may include arabinogalactan, galactan, or derivatives thereof. The invention provides a method for determining the metabolic viability or disease state of the target cells or organ by visualizing the extent, mode of uptake and excretion of the targeted x-ray contrast agent by x-ray or computer tomography.
Inventor(s): Jung; Chu (Arlington, MA), Palmacci; Stephen (Walpole, MA), Josephson; Lee (Arlington, MA)
Assignee: Advanced Magnetics, Inc. (Cambridge, MA)
Filing Date:Apr 02, 1991
Application Number:07/679,526
Claims:1. A method for X-ray imaging a specific population of cells in an animal comprising:

(i) forming a complex of a radiopaque label with a saccharide capable of being bound to a cell receptor and further being capable of being internalized by said cell via receptor mediated endocytosis;

(ii) administering to the animal a diagnostically effective amount of this complex;

(iii) forming an X-ray image of the animal.

2. A method according to claim 1, wherein the saccharide is a polysaccharide that is selected from the group consisting of arabinogalactan, mannose, degradation products of any of the foregoing and derivatives of any of the foregoing.

3. A method according to claim 2, wherein the polysaccharide is arabinogalactan modified with organic linking groups.

4. A method according to claim 3, wherein the organic linking group is selected from the group consisting of an aminopolycarboxylic acid, a polycarboxylic acid, a polyamine and an aminoalkanol.

5. A method according to claim 4, wherein the organic linking group is selected from the group consisting of diethylenetriaminepentaacetic acid, succinic acid, glutaric acid, ethylenediamine and aminoethanol.

6. A method according to claim 2, wherein the radiopaque label includes a compound containing iodine.

7. A method according to claim 6, wherein the radiopaque label is selected from the group consisting of a polyiodinated aromatic group and a polyiodinated aliphatic group.

8. A method according to claim 7, wherein the radiopaque label includes a compound selected from the group consisting of ioversol, metrizoic acid and 3-amino-2,4,6-triiodobenzoic acid.

9. A method according to claim 4, wherein the radiopaque label includes a compound containing iodine.

10. A method according to claim 9, wherein the radiopaque label is selected from the group consisting of a polyiodinated aromatic group and a polyiodinated aliphatic group.

11. A method according to claim 10, wherein the radiopaque label includes a compound selected from the group consisting of ioversol, metrizoic acid and 3-amino-2,4,6-triiodobenzoic acid.

12. A method according to claim 5, wherein the radiopaque label includes a compound containing iodine.

13. A method according to claim 12, wherein the radiopaque label is selected from the group consisting of a polyiodinated aromatic group and a polyiodinated aliphatic group.

14. A method according to claim 13, wherein the radiopaque label includes a compound selected from the group consisting of ioversol, metrizoic acid and 3-amino-2,4,6-triiodobenzoic acid.

15. A method according to claim 1, wherein the saccharide is attached to a compound that is incapable of performing receptor mediated endocytosis, providing a complex of the composition and the saccharide, wherein the resulting complex is capable of interacting with a cell receptor and performing receptor mediated endocytosis.

16. A method according to claim 1, wherein the saccharide is galactose.

17. A method according to claim 16, wherein the saccharide is galactose modified with organic linking groups.

18. A method according to claim 17, wherein the radiopaque label includes 2,3,5-triiodobenzyl alcohol.
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