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

Abstract

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 patientsmore » developed endogenous human anti-murine immunoglobulin antibody 2 to 3 weeks after treatment.« less

Authors:
; ; ; ; ; ;  [1]
  1. Hammersmith Hospital, London (England)
Publication Date:
OSTI Identifier:
7026058
Resource Type:
Journal Article
Journal Name:
Cancer Research; (USA)
Additional Journal Information:
Journal Volume: 50:3; Journal ID: ISSN 0008-5472
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; MONOCLONAL ANTIBODIES; BLOOD-PLASMA CLEARANCE; NEOPLASMS; RADIOIMMUNOTHERAPY; OVARIES; BONE MARROW; GLYCOPROTEINS; IMMUNOGLOBULINS; IODINE 131; LIVER; PATIENTS; RADIATION DOSES; ANIMAL TISSUES; ANTIBODIES; BETA DECAY RADIOISOTOPES; BETA-MINUS DECAY RADIOISOTOPES; BODY; CLEARANCE; DAYS LIVING RADIOISOTOPES; DIGESTIVE SYSTEM; DISEASES; DOSES; FEMALE GENITALS; GLANDS; GLOBULINS; GONADS; HEMATOPOIETIC SYSTEM; IMMUNOLOGY; IMMUNOTHERAPY; INTERMEDIATE MASS NUCLEI; IODINE ISOTOPES; ISOTOPES; MEDICINE; NUCLEAR MEDICINE; NUCLEI; ODD-EVEN NUCLEI; ORGANIC COMPOUNDS; ORGANS; PROTEINS; RADIOIMMUNOLOGY; RADIOISOTOPES; RADIOLOGY; RADIOTHERAPY; THERAPY; TISSUES; 550604* - Medicine- Unsealed Radionuclides in Therapy- (1980-)

Citation Formats

Stewart, J S, Sivolapenko, G B, Hird, V, Davies, K A, Walport, M, Ritter, M A, and Epenetos, A A. Clearance of sup 131 I-labeled murine monoclonal antibody from patients' blood by intravenous human anti-murine immunoglobulin antibody. United States: N. p., 1990. Web.
Stewart, J S, Sivolapenko, G B, Hird, V, Davies, K A, Walport, M, Ritter, M A, & Epenetos, A A. Clearance of sup 131 I-labeled murine monoclonal antibody from patients' blood by intravenous human anti-murine immunoglobulin antibody. United States.
Stewart, J S, Sivolapenko, G B, Hird, V, Davies, K A, Walport, M, Ritter, M A, and Epenetos, A A. 1990. "Clearance of sup 131 I-labeled murine monoclonal antibody from patients' blood by intravenous human anti-murine immunoglobulin antibody". United States.
@article{osti_7026058,
title = {Clearance of sup 131 I-labeled murine monoclonal antibody from patients' blood by intravenous human anti-murine immunoglobulin antibody},
author = {Stewart, J S and Sivolapenko, G B and Hird, V and Davies, K A and Walport, M and Ritter, M A and Epenetos, A A},
abstractNote = {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.},
doi = {},
url = {https://www.osti.gov/biblio/7026058}, journal = {Cancer Research; (USA)},
issn = {0008-5472},
number = ,
volume = 50:3,
place = {United States},
year = {Thu Feb 01 00:00:00 EST 1990},
month = {Thu Feb 01 00:00:00 EST 1990}
}