FRACTIONATED INTRAVENOUS ADMINISTRATION OF Y-90 LABELED B72.3 GYK-DTPA IMMUNOCONJUGATE IN BEAGLE DOGS

B72.3, a monoclonal antibody with reactivity against human adenocarcin omas, was coupled with linker chelator GYK DTPA using carbohydrate med iated conjugation chemistry and radiolabeled with yttrium-90. Single a nd double intravenous injections of radioimmunoconjugate were compared for acute and late normal tissue toxicity in 15 beagle dogs. The seco nd injection was given 4 or 8 days after the first. Pharmacokinetics o f the radioimmunoconjugate in blood, bone marrow and urine were simila r for first and second injections. Only bone marrow (acute) and liver (late) toxicity were observed. Both liver and bone marrow toxicity wer e decreased by fractionation of the injections. After double injection s, the total equitoxic dose was 15 and 60% higher for bone marrow and liver toxicity, respectively. The mechanisms of normal tissue protecti on offered by fractionated radioimmunoglobulin therapy (RIT) remain to be defined. Fractionated RIT will have a better therapeutic ratio tha n single injection RIT, if antitumor effects appear to be less suscept ible to fractionation than normal tissues.