A technique to prepare boronated B72.3 monoclonal antibody for boron neutron capture therapy.
B72.3 monoclonal antibody has been successfully boronated using mercaptoundecahydro-closo-dodecaborate (boron cage compound). The reagent was incorporated by first reacting the lysine residues of the antibody with m-maleimidobenzoyl succinimide ester (MBS), followed by Michael addition to the maleimido group by the mercapto boron cage compound to form a physiologically stable thioether linkage. Boron content of the antibody was determined by atomic absorption spectroscopy. For biodistribution studies, boronated antibody was radioiodinated with idogen. 125I-labeled and boronated B72.3 monoclonal antibody demonstrated clear tumor localization when administered via tail vein injections to athymic nude mice bearing LS174-T tumor xenografts. Boronated antibody was calculated to deliver 10(6) boron atoms per tumor cell. Although this falls short of the specific boron content originally proposed as necessary for boron neutron capture therapy (BNCT), recent calculations suggest that far fewer atoms of 10B per tumor cell would be necessary to effect successful BNCT when the boron is targeted to the tumor cell membrane.
Ranadive
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Department of Radiation Oncology, University of Pittsburgh, PA 15213.
Rosenzweig
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Epperly
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Bloomer
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D000230:Adenocarcinoma / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis* / Q000737:chemistry / Q000627:therapeutic use; D001894:Borohydrides; D001895:Boron / Q000032:analysis; D016754:Boron Neutron Capture Therapy; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D013054:Spectrophotometry, Atomic; D013438:Sulfhydryl Compounds; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D001894:Borohydrides; D013438:Sulfhydryl Compounds; C014651:mercaptoundecahydrododecaborate; D001895:Boron