KINETICS AND TISSUE DISTRIBUTION OF THE RADIOLABELED CHIMERIC MONOCLONAL-ANTIBODY MOV18 IGG AND F(AB')(2) FRAGMENTS IN OVARIAN-CARCINOMA PATIENTS

Twenty-four patients suspected of having ovarian carcinoma received i. v. injection with a combination of radiolabeled intact IgG (1 mg) and F(ab')2 fragments (1 mg) of the chimeric monoclonal antibody MOv18, ea ch form labeled with 1.85 MBq I-131 or I-125. Laparotomy was performed either 2 or 6 days after injection, and the uptake of radioactivity w as determined in a total of 329 biopsies of normal and malignant tissu es. The mean elimination half life in plasma of cMOv18 IgG and F(ab')2 was 70 +/- 8 (SD) and 20 +/- 5 h, respectively. The mean uptake of Ig G in tumor biopsies was 3.6-fold higher two days after injection and 6 .9-fold higher than the uptake of F(ab')2 6 days after injection. Upta ke in normal tissues was 3.3 and 5.5 times higher for IgG at 2 and 6 d ays, respectively. Two days after injection, the mean ratio of the upt ake in tumor:normal tissue/patient was 3.8 +/- 1.5 and 4.0 +/- 1.8 for radiolabeled cMOv18 IgG and F(ab')2, respectively. Six days after inj ection, this was 6.7 +/- 4.7 for Ig G and 5.7 +/- 4.1 for F(ab')2. cMO v18 IgG has a longer circulation time in blood, a higher uptake in tum or and normal tissues, and a longer retention time compared to the F(a b')2 fragments. However, the tumor:normal tissue ratios are similar. T he results do not warrant a definite conclusion as to which antibody f orm is most suitable for therapeutic application of antibodies but pro vide a more firm basis for rational design of therapeutic targeting st udies using immunoconjugates.