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The Journal of Nuclear Medicine Vol. 26 No. 12 1418-1423
© 1985 by Society of Nuclear Medicine
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In Vivo Kinetics of Radiolabeled Monoclonal Anti-CEA Antibodies in Animal Models

Phillip L. Hagan, Samuel E. Halpern, Agnes Chen, Lakshmy Krishnan, James Frincke, Richard M. Bartholomew, Gary S. David and Dennis Carlo

Veterans Administration Medical Center and University of California, San Diego
Hybritech, Inc., La Jolla, California

Correspondence: For reprints contact: Samuel E. Halpern, MD, Dept. of Nuclear Medicine, VA Medical Center, 3350 La Jolla Village Dr. San Diego, CA 92161.

ABSTRACT

Studies were performed to determine the effect of the radiolabel and circulating carcinoembryonic antigen (CEA)on the pharmacodynamics of monoclonal anti-CEA antibodies (MoAbs).The studies were performed in normal BALB/c mice and in nude mice bearing human colon tumors. Three different tumors were used, each of which produced CEA levels characteristic of that particular tumor's secretory rate. The CEJ-326 MoAb labeled with either 111In or 125I was used in all studies. arculating CEA induced the removal of 125I and 111In MoAbs from the vascular compartment Liver concentrations of 111In increased and 125I levels decreased as the CEA secretory rate of the tumor rose. This indicates that circulating CEA complexes form in the vascular compartment which, in an animal model, are removed by the liver and spleen. This results in decreased tumor uptake of the labeled MoAb. The iodinated MoAb complexes are dehalogenated while the 111In is retained by the liver. This dehalogenation may account for the relatively low liver activity observed in radioimmunoimaging with intact radioiodinated anti-CEA MoAbs, provided the CEA complexes are similarly removed from the vascular compartment by the human liver.







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