Development and evaluation of copper-67 and samarium-153 labeled conjugates for tumor radioimmunotherapy

The potential of utilizing receptor-specific agents such as monoclonal antibodies (MAb), and MAb-derived smaller molecules, as carriers of radionuclides for the selective destruction of tumors has stimulated much research activity. The success of such applications depends on many factors, especially the tumor binding properties of the antibody reagent, the efficiency of labeling and in-vivo stability of the radioconjugate and, on the careful choice of the radionuclide best suited to treat the tumor under consideration. The radiolabeled antibody technique for radioimmunotherapy (RIT), however, has experienced many limitations, and its success has not matched the expectations that were raised more than a decade ago. The problems that have been identified include: (i) degradation of antibody immunoreactivity resulting from chemical manipulations required for labeling; (ii) lack of suitable radioisotopes and methods for stable attachment of the radiolabel; (iii) in-vivo instability of the radioimmunoconjugates; (iv) excessive accumulation of activity in non-target locations; and (v) lack of radioimmunoconjugate accessibility to cells internal to a tumor mass. A careful choice of the radionuclide(s) best suited to treat the tumor under consideration is one of the most important requirements for successful radioimmunotherapy. This study evaluates copper 67 and samarium 153 for tumor radioimmunotherapy