Labeling of monoclonal antibodies with a 67Ga-phenolic aminocarboxylic acid chelate. Part I. Chemistry and labeling technique.
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 tightly 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 degrees 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.
D000818:Animals; D000911:Antibodies, Monoclonal; D002850:Chromatography, Gel; D005029:Ethylenediamines; D005710:Gallium Radioisotopes; D007553:Isotope Labeling / Q000379:methods; D051381:Rats; D013329:Structure-Activity Relationship; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D005029:Ethylenediamines; D005710:Gallium Radioisotopes; C011813:ethylenediamine-N,N'-bis(2-hydroxyphenylacetic acid)