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Kinetics and Tissue Distribution of the Radiolabeled Chimeric Monoclonal Antibody MOv18 IgG and F(ab')₂ Fragments in Ovarian Carcinoma Patients¹

Departments of Obstetrics and Gynecology [M. R. B., P. K., C. J. M. M., C. W. B.], Nuclear Medicine [W. d. H., J. C. R.], Medical Oncology [J. B. V.], and Pathology [J. P. A. B.], Free University Hospital, De Boelelaan 1117, 1081 HV Amsterdam, and Department of Gynecology [T. J. M. H.], Netherlands Cancer Institute, Plesmalaan 121, 1066 CX, Amsterdam, The Netherlands

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, each form labeled with 1.85 MBq ¹³¹I or ¹²⁵I. Laparotomy was performed either 2 or 6 days after injection, and the uptake of radioactivity was determined in a total of 329 biopsies of normal and malignant tissues.

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 IgG 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. Uptake in normal tissues was 3.3 and 5.5 times higher for IgG at 2 and 6 days, respectively. Two days after injection, the mean ratio of the uptake 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 injection, this was 6.7 ± 4.7 for Ig G and 5.7 ± 4.1 for F(ab')₂.

cMOv18 IgG has a longer circulation time in blood, a higher uptake in tumor and normal tissues, and a longer retention time compared to the F(ab')₂ fragments. However, the tumor:normal tissue ratios are similar. The results do not warrant a definite conclusion as to which antibody form is most suitable for therapeutic application of antibodies but provide a more firm basis for rational design of therapeutic targeting studies using immunoconjugates.

¹ This study was supported by Clinical Research Grant NWO 900-716-020 of the Netherlands Organization for Scientific Research and by Grant 92-05 from the Biocare Foundation.

² To whom requests for reprints should be addressed, at Department of Obstetrics and Gynecology, Free University Hospital, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.

Received 4/ 5/93. Accepted 9/ 8/93.

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