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Title: Reduction - Mediated <sup>99m</sup>Tc - Labeling of Antitumor Monoclonal Antibodies : Effect of Increasing Specific Activity on Antibody Binding Kinetics
Authors: Vipa Boonkitticharoen
Duangpen Puchinda
Puthiporn Chouplywech
Wirawat Jalayondeja
Mahidol University
Keywords: Medicine
Issue Date: 1-Oct-1998
Citation: Journal of the Medical Association of Thailand. Vol.81, No.10 (1998), 740-748
Abstract: Reduction-mediated 99mTc-labeling of antibodies has gained widespread acceptance in preparation of tumor imaging agents. Increased specific activity to enhance detection signals has raised the question of whether such an attempt would cause change in antibody binding kinetics. To answer this question, two antitumor monoclonal antibodies, i.e. IOR-CEA (IgG1) and EMD (IgG2a) were labeled with 99mTc to yield specific activities ranging from 549-4414 MBq/mg. Regression analysis of the binding data revealed that the binding kinetics of IOR-CEA were shifted from monovalent to bivalent binding upon increasing the specific activities. This phenomenon of affinity enhancement was confirmed by the dissociation study where we found soluble CEA had greater difficulty in extracting the cell-bound IOR-CEA labeled at higher specific activity. The bivalent binding was further supported by the finding that IOR-CEA with higher specific activities delivered less than expected radioactivity to tumor targets despite their immunoreactivities being well preserved. For EMD, the kinetics seemed to be shifted from bivalent to monovalent interaction. At higher specific activities, adverse changes in immunoreactivity were recognized. Breakage of EMD into 99mTc.Fab fragments was likely to occur and was supported by the observation that EMD delivered more than expected radioactivities to target cells upon increasing specific activity. Precaution should be taken when one deals with high specific activity labeling since this might alter the antibody binding kinetics either favorably or unfavorably.
ISSN: 01252208
Appears in Collections:Scopus 1991-2000

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