Paxton R J, Beatty B G, Hawthorne M F, Varadarajan A, Williams L E, Curtis F L, Knobler C B, Beatty J D, Shively J E
Division of Immunology, Beckman Research Institute of the City of Hope, Duarte, CA 91010.
Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3387-91. doi: 10.1073/pnas.88.8.3387.
A novel transition metal complex, Venus flytrap cluster (VFC), is described for the preparation of radio-labeled antibodies. VFC contained 57Co, which was held tightly between the faces of two covalently bridged carborane ligands by cluster bonding of the metal with appropriate ligand orbitals. Anti-carcinoembryonic antigen monoclonal antibody T84.66 was conjugated to 57Co-VFC with full retention of immunological activity. Biodistribution studies in nude mice bearing carcinoembryonic antigen-producing tumors showed excellent tumor localization of 57Co-VFC-T84.66. The accumulation of radionuclide in normal liver was low and independent of dose, which may reflect the stability of the radionuclide complex. These results presage the use of VFC systems for binding transition metals that are clinically useful for radioimmunodiagnosis and radioimmunotherapy.
描述了一种新型过渡金属配合物——捕蝇草簇合物(VFC),用于制备放射性标记抗体。VFC含有57Co,通过金属与适当配体轨道的簇键合,57Co紧密地保持在两个共价桥连碳硼烷配体的面之间。抗癌胚抗原单克隆抗体T84.66与57Co-VFC偶联,免疫活性完全保留。在携带产生癌胚抗原肿瘤的裸鼠中进行的生物分布研究表明,57Co-VFC-T84.66在肿瘤中的定位极佳。放射性核素在正常肝脏中的蓄积较低且与剂量无关,这可能反映了放射性核素配合物的稳定性。这些结果预示着VFC系统可用于结合对放射免疫诊断和放射免疫治疗具有临床应用价值的过渡金属。