Radiolabeling and Biotinylation of Internalizing Monoclonal Antibody Chimeric BR96: Potential Use for Extracorporeal Immunoadsorption

Abstract: In this thesis, methodology of radiolabeling and simultaneous biotinylation for internalizing monoclonal antibody (MAb) chimeric BR96 (chiBR96) have been investigated by using three element groups of potential therapeutic radionuclides iodine, indium and rhenium, and their different labeling methods. The biodistribution and kinetics of biotinylated and radiolabeled chiBR96 have been studied in colon carcinoma isografted rats. The potential use of ECIA, based on the biotin-avidin concept, has been evaluated and compared with the approach of avidin "chase" in the same animal tumor model with respect to an enhancement of tumor-to-normal tissue (T/N) activity ratio. In vivo stability and tumor targeting capacity of biotinylated 111In-chiBR96 using the chelate SCN-Bz-CHX-A-DTPA, have increased compared with two other chelates used in this study. Conjugate NSTBB has been successfully used for iodination of chiBR96 combined with biotinylation, in contrast to the combination with electrophilic labeling method