Complex for in-vivo target localization

Details Complex for in-vivo target localization Complex for in-vivo target localization

1990-05-17

1993-06-01

Nucker, Christine M.

Chemistry: natural resins or derivatives; peptides or proteins;

Proteins, i.e., more than 100 amino acid residues

Albumin

530363, 5303911, 5303913, 5303915, 5303917, 5303919, 530409, 536 51, 536112, 424 11, 424 8591, 424450, C07K 1710, C07K 1514, A61K 3944, A61K 4748

Patent

active

052161307

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 those coated with native dextran (T.sub.1/2 =35-50 min). These labelled albumin targeting microspheres may be used to detect a variety of sites of clinical interest using non-invasive external imaging devices and may be employed to carry therapeutic agents to these sites.

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