Clearance of sup 131 I-labeled murine monoclonal antibody from patients' blood by intravenous human anti-murine immunoglobulin antibody

• Published in: Cancer research (Chicago, Ill.) Vol. 50:3
• Main Authors: Stewart, J.S., Sivolapenko, G.B., Hird, V., Davies, K.A., Walport, M., Ritter, M.A., Epenetos, A.A.
• Format: Journal Article
• Language: English
• Published: United States 01.02.1990
• Subjects: 550604 - Medicine- Unsealed Radionuclides in Therapy- (1980-); ANIMAL TISSUES; ANTIBODIES; BETA DECAY RADIOISOTOPES; BETA-MINUS DECAY RADIOISOTOPES; BLOOD-PLASMA CLEARANCE; BODY; BONE MARROW; CLEARANCE; DAYS LIVING RADIOISOTOPES; DIGESTIVE SYSTEM; DISEASES; DOSES; FEMALE GENITALS; GLANDS; GLOBULINS; GLYCOPROTEINS; GONADS; HEMATOPOIETIC SYSTEM; IMMUNOGLOBULINS; IMMUNOLOGY; IMMUNOTHERAPY; INTERMEDIATE MASS NUCLEI; IODINE 131; IODINE ISOTOPES; ISOTOPES; LIVER; MEDICINE; MONOCLONAL ANTIBODIES; NEOPLASMS; NUCLEAR MEDICINE; NUCLEI; ODD-EVEN NUCLEI; ORGANIC COMPOUNDS; ORGANS; OVARIES; PATIENTS; PROTEINS; RADIATION DOSES; RADIOIMMUNOLOGY; RADIOIMMUNOTHERAPY; RADIOISOTOPES; RADIOLOGY; RADIOLOGY AND NUCLEAR MEDICINE; RADIOTHERAPY; THERAPY; TISSUES
• ISSN: 0008-5472; 1538-7445

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.