Enhanced Effect of Radiolabeled Monoclonal Antibody Uptake in Tumor with Defibrinating Agents

Akihiko Takeda, Takeyoshi Miyoshi, Toshiyuki Kikuchi, Masahiko Ozaki, Takamitsu Ariga, Tohru Nagashima, Yasuhisa Abe, Wataru Takayama, Noboru Arimizu*, Kuichi Isono

Second Department of Surgery, School of Medicine, Chiba University
*Department of Radiology, School of Medicine, Chiba University

Radiolabeled monoclonal antibodies against a variety of cancer associated antigens have already been clinically used for tumor imaging, but reports of specific antibody uptake by tumors are still rare. Therefore tumor targeting and localization experiments were performed by intravenously injecting nude mice bearing LS-180 (colon carcinoma) with 1251-labeled antibody (anti-CEA; 1B2), along with defibrinating agents urokinase and low molecular weight dextran to improve the vascular permeability of the tumor. Tumor activity 72 hr after administration, expressed as counts per minutes per gram of tumor and the percentage of the injected dose per gram of tumor in animals given the defibrinating agents was significantly higher than in the control group. Accumulation of the antibody in the tumor after administration of the mixture of these two agents was 48.3% higher than the control level, and the higher the number of doses and the concentration of the mixture administered to tumor bearing mice, the higher was the specific uptake by the tumor. However nonspecific high accumulation in normal organs, such as the liver, kidneys and spleen, was not observed. Therefore the tumor/blood ratio and the tumor/liver ratio were increased. These results indicated that the mixture of urokinase and low molecular weight dextran could be a useful tool for radioimmunodetection by making the radioactivity of the transplanted tumors high enough to distinguish them from normal organs.

Key words
monoclonal antibody, radioimmunodetection, defibrinating agents, tumor vascular permeability, tumor accumulation

Reprint requests
Akihiko Takeda Second Department of Surgery, School of Medicine, Chiba University
1-8-1 Inohana, Chiba-city, 280 JAPAN

Accepted
March 13, 1991

To read the PDF file you will need Abobe Reader installed on your computer.