Present Status and Future Prospects in Application of Radiolabeled Monoclonal Antibodies in Diagnosis and Therapy

Abstract

Tumor localization trials with radiolabeled polyclonal antibodies began 40 years ago based on the idea that antibodies against tumor-associated antigens could bring sufficient radioactivity to the tumor for efficient diagnosis and therapy of cancer [5, 11]. The development of the hybridoma technique by Kohler and Milstein for production of monoclonal antibodies (MAb) was an important contribution to further applications in the field of immunoscintigraphy and radioimmunotherapy [8]. Despite promising results concerning the accumulation of MAb to tumor-associated antigens in xenotransplanted human tumors in nude mice, with uptake values of 70% of injected dose per gram of tissue [18], the results in clinical application did not fulfill the expectations. In most clinical trials very tiny amounts of the injected dose, usually between 0.001% and 0.05%, were taken up per gram of tumor tissue, with the rest circulating in blood or localized in normal tissue such as liver and kidney [9]. Therefore tumor-to-background ratios of radioactivity, essential for scintigraphic imaging of the tumor and for radioimmunotherapy, remain too low.