Radionuclide antibody coupling

A method of preparing a metal radionuclide-labeled protein from a protein precursor having at least one disulfide linkage, the method comprising:

• reacting said protein precursor with a disulfide reducing agent to form a dimercaptoprotein;
• stabilizing said dmercaptoprotein against inactivation by reaction of the dimercaptoprotein with a derivatizing agent for mercapto groups, thereby producing a derivatized protein having regenerable mercapto groups;
• regenerating said mercapto groups, thereby forming a regenerated dimercaptoprotein;
• and
• combining said regenerated dimercaptoprotein with .sup.99m Tc, .sup.186 Re, .sup.188 Re or .sup.67 Cu to form said metal radionuclide-labeled protein.

A method for direct technetium-99m labeling of a disulfide-containing protein, comprising:

• forming a labile, soluble complex of reduced technetium-99m;
• reacting said disulfide-containing protein with dithiothreitol to form a dimercaptoprotein;
• and
• combining said dimercaptoprotein with said labile, soluble complex of reduced technetium-99m in a reaction solution or buffer having a pH from about 5 to about 10.

A method for directly labeling a storage-stable dimercaptoprotein with a metal radionuclide, comprising:

• reacting a disulfide-containing protein with a reducing agent to form a dimercaptoprotein;
• lyophilizing said dimercaptoprotein, thereby forming a storage-stable dimercaptoprotein;
• rehydrating said storage-stable dimercaptoprotein, thereby forming a regenerated dimercaptoprotein;
• and
• combining said regenerated dimercaptoprotein with .sup.99m Tc, .sup.186 Re, .sup.188 Re or .sup.67 Cu to obtain said metal radionuclide-labeled protein.