Targeting protein-diagnostic/therapeutic agent conjugates having Schiff base linkages

A targeting protein conjugated to a radionuclide by a Schiff base linker and having the formula:

• ##STR27## wherein etc. "Ar" is a substituted or unsubstituted aryl group;
• "N" is a nitrogen atom;
• "C" is a carbon atom;
• "R" is H or an alkyl, aryl or heteroaryl substituent;
• and
• "Z" comprises a radionuclide selected from the group consisting of .sup.123 I, .sup.125 I, .sup.130 I, .sup.131 I, .sup.133 I, .sup.135 I, .sup.47 Sc, .sup.72 Se, .sup.90 Y, .sup.88 Y, .sup.97 Ru, .sup.119 Sb, .sup.197 Hg, .sup.211 At, .sup.212 Bi, .sup.212 Pb, .sup.111 In, .sup.67 Ga, .sup.68 Ga, .sup.67 Cu, .sup.75 Br, .sup.76 Br, .sup.99m Tc, .sup.18 F, .sup.188 Re, .sup.186 Re, .sup.203 Pb, .sup.64 Cu, .sup.105 Rh, .sup.198 Au and .sup.199 Au,
• and wherein the substituent of Ar, if present, is an electron-withdrawing group or an electron-donating group capable of modifying unreduced imine bond stability of the Schiff base linker, and wherein the Schiff base is formed by a process which comprises:
• reacting a non-oxidized and native amine-bearing or amine-derivatized targeting protein with aromatic aldehyde or ketone, wherein the aromatic aldehyde or ketone is directly conjugated to Z or indirectly conjugated to Z via a chelating ligand, to form a stabilized Schiff base linker, absent a subsequent stabilizing step with respect to the C=N bond,
• wherein antibody antigen binding antibody fragment carbohydrate content is not determinative of maximum possible aromatic aldehyde or ketone conjugation to the antibody or antigen binding antibody fragment.