Reduction-mediated 99mTc-labeling of antitumor monoclonal antibodies: effect of increasing specific activity on antibody binding kinetics.

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dc.contributor.authorBoonkitticharoen, Ven_US
dc.contributor.authorPuchinda, Den_US
dc.contributor.authorChouplywech, Pen_US
dc.contributor.authorJalayondeja, Wen_US
dc.date.accessioned2009-05-27T18:06:18Z
dc.date.available2009-05-27T18:06:18Z
dc.date.issued1998-10-06en_US
dc.descriptionChotmaihet Thangphaet.en_US
dc.description.abstractReduction-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 bindings 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.en_US
dc.description.affiliationDepartment of Radiology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.en_US
dc.identifier.citationBoonkitticharoen V, Puchinda D, Chouplywech P, Jalayondeja W. Reduction-mediated 99mTc-labeling of antitumor monoclonal antibodies: effect of increasing specific activity on antibody binding kinetics. Journal of the Medical Association of Thailand. 1998 Oct; 81(10): 741-9en_US
dc.identifier.urihttps://imsear.searo.who.int/handle/123456789/38465
dc.language.isoengen_US
dc.source.urihttps://www.mat.or.th/journal/all.phpen_US
dc.subject.meshAnimalsen_US
dc.subject.meshAntibodies, Monoclonal --diagnostic useen_US
dc.subject.meshAntibodies, Neoplasm --diagnostic useen_US
dc.subject.meshHumansen_US
dc.subject.meshIsotope Labeling --methodsen_US
dc.subject.meshMiceen_US
dc.subject.meshRadioimmunodetection --methodsen_US
dc.subject.meshReducing Agents --diagnostic useen_US
dc.subject.meshTechnetium --diagnostic useen_US
dc.subject.meshTumor Cells, Cultured --drug effectsen_US
dc.titleReduction-mediated 99mTc-labeling of antitumor monoclonal antibodies: effect of increasing specific activity on antibody binding kinetics.en_US
dc.typeJournal Articleen_US
dc.typeResearch Support, Non-U.S. Gov'ten_US
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