Differential chemical behavior of Humanized Monoclonal Antibodies in the radiolabeled with99mTc

摘要

The purpose of this work consisted in the comparison of the chemical behavior ofimmunoglobulins of different origin. The immunoglobulins were the human-IgG, the R3 and T1humanized monoclonal antibodies, and the ior t3 murine monoclonal antibody. The immunoglobulinswere reduced with sodium metabisulfite at a molar relation SMB: IgG of 950:1 for 45 minutes beforeradiolabeling with 99mTc. The formation of fragments and aggregates, and the immunoreactivity of themonoclonal antibodies were studied once concluded the reduction process. Also, comparative studiesof the radiochemical stability and challenges were carried out after radiolabeled. Our results indicateddifferences in the chemical behavior among the immunoglobulins after their reduction with sodiummetabisulfite. The first difference observed was a higher generation of fragments in the humanizedmonoclonal antibodies, the second one was a higher formation of free sulphydryl groups and the thirdone was an increased percentage of dissociation when the radiolabeled humanized antibodies werechallenged with cysteine. These results demonstrated that the humanized antibodies were moresensitive to the reduction process, and once radiolabeled presented lower radiochemical parametersthan the murine antibody and the human IgG. This work demonstrated that the origin of theimmunoglobulin is an important element in its chemical and radiochemical behavior when sodiummetabisulfite was used as a reducing agent for radiolabeling with 99mTc.