Ma. Stalteri et al., SITE-SPECIFIC CONJUGATION AND LABELING OF PROSTATE ANTIBODY 7E11C5.3 (CYT-351) WITH TC-99M, European journal of nuclear medicine, 24(6), 1997, pp. 651-654
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.