SITE-SPECIFIC CONJUGATION AND LABELING OF PROSTATE ANTIBODY 7E11C5.3 (CYT-351) WITH TC-99M

Attachment of chelating agents to the sugar residues of antibodies for subsequent radiolabelling is an attractive approach since it may have less effect on the immunoreactivity than attachment through lysine re sidues, which are distributed throughout the antibody and may be prese nt near the antigen binding site. We have attached a new hydrazide-lin ked chelator CYT-395 (Cytogen Corp., Princeton, N.J.) to the sugar res idues of the anti-prostate monoclonal antibody 7E11C5.3 and optimised the conditions for labelling the conjugate with technetium-99m in orde r to compare the conjugate to 7E11C5.3 antibody labelled directly with technetium using a mercaptoethanol reduction technique, Labelling yie lds of 70%-90% were obtained at specific activities up to 2000 MBq/mg antibody. The stability of the technetium-labelled conjugate in plasma or to a challenge with 0.1 or 1.0 mM cysteine was similar to that of direct-labelled antibody. In nine patients with prostate cancer, the p lasma clearance of the labelled conjugate followed a two-compartment m odel, with an average beta-phase half-life of 31.4 +/- 3.9 h. The aver age urinary clearance at 24 h was 15.3 +/- 5.0% of the injected dose. In this group of patients there was no significant difference between the blood and urine clearance of the labelled conjugate, and the clear ances of the direct-labelled antibody.