Improved immunotargeting of tumors with biotinylated monoclonal antibodies and radiolabeled streptavidin

Tumor localization with radiolabeled monoclonal antibodies is limited by the low uptake of label by tumor which has been reported both in animal and patient studies. The very high affinity of avidin or streptavidin for biotin (K(d)= 10^-15M) suggests that improvement may result if radiolabeled streptavidin is used to target radionuclides to biotinylated monoclonal antibodies previously localized in tumors. Using three experimental tumor models and corresponding monoclonal antibodies, we attempted to explore this hypothesis and optimize the conditions required for the enhancement of radiolabel delivery (immunotargeting) in tumor-bearing nude mice. In particular, the number of biotin groups per antibody molecule and the elapsed time required before the administration of radiolabeled streptavidin were studied. Biodistribution analyses, performed 24 hrs after the injection of radiolabeled streptavidin, demonstrated that treatment of tumor-bearing nude mice with biotinylated monoclonal antibodies resulted in a 1.3-2.6 fold increase in radiolabel localization in tumor compared to directly labeled antibodies used as controls. Furthermore, tumor/organ ratios showed marked improvement and external imaging studies in individual mice demonstrated more rapid and improved tumor uptake. These results indicate the feasibility of using streptavidin as a possible universal delivery agent for radionuclides in the radioimmunodiagnosis and therapy of tumors.