Bifunctional chelating agents for radiometal-labeled monoclonal antibodies

Recently there has been a great deal of interest in attaching metal ions to proteins. Since a variety of metal ions possess interesting chemical, physical, nuclear, and magnetic properties, they can be employed to probe the behavior of biologic systems. For example, fluorescent-labeled proteins, proteins containing paramagnetic chelates, and proteins bound to photosensitive metal chelates have been studied [1]. When the metal is radioactive and the protein is an antibody that has high specficity for tumors, the resultant chelate-antibody conjugate can be employed for cancer diagnosis. Monoclonal antibodies that possess a high affinity for tumor-associated antigens can now be prepared due to the technique developed by Kohler and Milstein [2]. By attaching a radionuclide to such a monoclonal antibody of predetermined specificity, one can selectively localize the radioactivity at tumor sites. This principle has been employed in developing new pharmaceuticals for use in radioimmuno-diagnosis and, in certain cases, radioimmunotherapy [3,4]. In this review we will briefly examine the chemical aspects of bifunctional chelating agents for linking radiometals to monoclonal antibodies.