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Clearance of ¹³¹I-labeled Murine Monoclonal Antibody from Patients' Blood by Intravenous Human Anti-Murine Immunoglobulin Antibody

Imperial Cancer Research Fund & Department of Clinical Oncology, Hammersmith Hospital [J. S. W. S., V. H., A. A. E.], and the Department of Immunology [G. B. S., M. A. R.] and Rheumatology [K. A. A. D., M. W.], The Royal Postgraduate Medical School, Du Cane Road, London W12 0NN, United Kingdom

Five patients treated with intraperitoneal ¹³¹I-labeled mouse monoclonal antibody for ovarian cancer also received i.v. exogenous polyclonal human anti-murine immunoglobulin antibody. The pharmacokinetics of ¹³¹I-labeled monoclonal antibody in these patients were compared with those of 28 other patients receiving i.p.-radiolabeled monoclonal antibody for the first time without exogenous human anti-murine immunoglobulin, and who had no preexisting endogenous human anti-murine immunoglobulin antibody.

Patients receiving i.v. human anti-murine immunoglobulin antibody demonstrated a rapid clearance of ¹³¹I-labeled monoclonal antibody from their circulation. The (mean) maximum ¹³¹I blood content was 11.4% of the injected activity in patients receiving human anti-murine immunoglobulin antibody compared to 23.3% in patients not given human anti-murine immunoglobulin antibody. Intravenous human anti-murine immunoglobulin antibody decreased the radiation dose to bone marrow (from ¹³¹I-labeled monoclonal antibody in the vascular compartment) 4-fold. Following the injection of human anti-murine immunoglobulin antibody, ¹³¹I-monoclonal/human anti-murine immunoglobulin antibody immune complexes were rapidly transported to the liver. Antibody dehalogenation in the liver was rapid, with 87% of the injected ¹³¹I excreted in 5 days. Despite the efficient hepatic uptake of immune complexes, dehalogenation of monoclonal antibody was so rapid that the radiation dose to liver parenchyma from circulating ¹³¹I was decreased 4-fold rather than increased. All patients developed endogenous human anti-murine immunoglobulin antibody 2 to 3 weeks after treatment.

¹ To whom requests for reprints should be addressed, at Department of Clinical Oncology, Hammersmith Hospital, Du Cane Road, London W12 ONN.

Received 1/30/89. Revised 10/ 2/89. Accepted 10/16/89.