Complex for in-vivo target localization

US5216130A · kind A · utility

Assignee

• Albany Medical College · US

Inventors

• Bruce R. Line · Delmar, US
• Peter Weber · Delmar, US

Key dates

• Filing date: May 17, 1990
• Grant date: Jun 1, 1993
• Expiry date: May 17, 2010

Classification

• Technology area (CPC A): Human Necessities
• CPC primary: A61N5/1069
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

To localize targets within the body (i.e., fixed intravascular antigens on emboli, neovascular endothelium, endothelium altered by regional inflammation) antibodies are linked via dextran spacer arms to rapidly cleared, Tc-99m labeled, microspheres. A micron-sized, albumin microsphere has been synthesized that is designed to enhance target surface interaction and to have a high antibody loading capacity. Stable, hydrophilic microspheres are produced from a pH dependent refolding of albumin followed by heat annealing. To couple dextran, the microspheres are derivatized with succinic anhydride and then linked via carbodiimide to succinic dihydrazide. After periodate oxidized dextran forms hydrazone linkages to the microspheres, additional dihydrazide coupled to the dextran spacer arm is used to link periodate oxidized IgG via its Fc domain carbohydrate. A milligram of the resulting 0.5-1.0 micron microspheres contains 50 to 350 ug of dextran and up to 10.sup.5 covalently bound IgG molecules per microsphere. Microspheres exposed to SnCl.sub.2 can be labeled with 90 Mci/mg of Tc-99m. Spheres with high levels of dextran SDH clear the blood rapidly (T.sub.1/2 =2.6-4 min) compared to thos…