PRECLINICAL EVALUATION OF INTRAVENOUSLY ADMINISTERED IN-111 LABELED AND Y-90 LABELED B72.3 IMMUNOCONJUGATE (GYK-DTPA) IN BEAGLE DOGS

B72.3, a monoclonal antibody with reactivity against human adenocarcin omas was obtained from the Cytogen Corporation in the form of an immun oconjugate coupled with linker chelator GYK-DTPA by using proprietary carbohydrate directed site specific chemistry. The immunoconjugate was radiolabeled with indium-111 or yttrium-90. A preclinical analysis wa s performed in 10 normal beagle dogs. The pharmacokinetics of intraven ously administered indium- and yttrium-labeled immunoconjugates were c ompared serially in blood, bone marrow and urine samples. Compared to Y-90 less of the In-111 label ended up in urine and more was found in blood and bone marrow. Indium-labeled B72.3 GYK-DTPA had relatively hi gher uptake in most glandular tissues than In-111-labeled antiferritin immunoconjugate. Bone marrow toxicity was the dose limiting side effe ct after intravenous infusion of Y-90-labeled B72.3 GYK-DTPA. Toxicity was also observed in the liver but not in other organ systems. Recent ly other investigators obtained similar results with these immunoconju gates in human patients. A preclinical pharmacokinetic analysis of rad ioimmunoconjugates in beagle dogs provided useful information regardin g bone marrow toxicity, liver toxicity and in vivo instability of the immunoconjugate. Data suggest that for future trials in human patients , a more stable chelated immunoconjugate for yttrium is needed to achi eve less liver uptake and a better correlation with the In-111-labeled product than the Y-90-labeled B72.3 GYK-DTPA used in this investigati on.