Monoclonal antibody CO17-1A, which has specificity for colorectal and
pancreatic carcinomas, was radiolabeled with the pure beta emitter, 90Y, by either the cyclic diethylenetriaminepentaacetic
acid (
DTPA)
anhydride technique or by a site-specific bifunctional chelate technique using 1-(p-aminobenzyl)DTPA (p-NH2-Bz-DTPA). Female nude mice bearing SW 948 human
colorectal carcinoma xenografts were given
injections i.v. of 90Y-labeled
monoclonal antibody CO17-1A at dosages of 100, 150, and 200 muCi/25 g
body weight. Unlabeled CO17-1A (100 micrograms/25 g
body weight) was coadministered. In animals receiving 90Y-CO17-1A prepared by the
cyclic DTPA anhydride technique,
tumor volume was unchanged from base line at a dose of 200 microCi/25 g. As the dosage of 90Y-CO17-1A increased, the rate of
tumor growth decreased, but all experimental animals in this group died between 14 and 21 days. In contrast, CO17-1A radiolabeled with 90Y by the site-specific p-NH2-Bz-DTPA bifunctional chelate technique produced a maximum
tumor volume reduction of 87% in the 200 microCi/25 g group by day 15, and no deaths were noted in any of the 90Y-CO17-1A-treated groups for 71 days. Dose-response curves again showed increased tumoricidal effects with increased dosages of 90Y-CO17-1A. S-2-(3-Aminopropylamino)ethylphosphorothioic
acid, commonly known as
WR-2721, is a
radioprotective drug which has been shown to protect against bone marrow depression in irradiated humans. No protection was observed when
WR-2721 was used as an adjunct to treatment with 90Y-CO17-1A prepared by either the
cyclic DTPA anhydride technique or the site-specific p-NH2-Bz-DTPA technique. When the site-specific p-NH2-Bz-DTPA technique was used, the reduction in WBC and
hemoglobin levels correlated with increasing bone marrow toxicity at higher doses. We conclude that CO17-1A labeled with 90Y via the site-specific p-NH2-Bz-DTPA technique has potential for
radioimmunotherapy of human
colorectal carcinoma.