Labeling of monoclonal antibodies with a 67Ga-phenolic aminocarboxylic acid chelate

As a chelating agent for labeling antibodies (Abs) with metallic radionuclides, a propionic acid substituted ethylenediamine N,N-di-[(o-hydroxyphenyl) acetic acid] (P-EDDHA), which tighly complexes ⁶⁷Ga, was synthesized. The ⁶⁷Ga-P-EDDHA chelate was coupled in aqueous solution to IgG at a molar ratio of 1:1 via carbodiimide. The average coupling yield was 15%. A specific activity of 4 mCi/mg IgG could be obtained with commercially supplied ⁶⁷Ga. In vitro stability was evaluated in human serum at 37° C and showed a half-life of about 120 h for the release of ⁶⁷Ga from the labeled Ab during the initial phase of incubation. This in vitro halflife is similar to that measured for ¹¹¹In-DTPA labeled Abs. Because of the high stability of the ⁶⁷Ga-P-EDDHA chelate, the in vivo formation of radioactive labeled transferrin by transchelation, as described for ¹¹¹In-DTPA labeled Abs, should, however, be reduced by this labeling technique.