Experimental tumor targeting with radiolabeled ligands

BACKGROUND: Approaches have been developed in animal models to increase the localization of radiolabeled ligands (monoclonal antibodies and peptides) in tumors, to reduce their uptake in normal tissues, and to thus improve the tumor/normal tissue uptake ratios so that higher and more frequent doses of radionuclide could be used for radioimmunotherapy. METHODS: These approaches to increase the localization of radiolabeled ligands in tumors involve the following three general strategies: (1) modifying ligands or radiolabeling techniques, (2) increasing blood and normal tissue clearance of radiolabeled ligands, and (3) modifying tumor delivery, tumor antigen, or receptor expression or increasing tumor vascular permeability or blood flow. RESULTS: The use of such animal models permits the assessment of a wide range of ligands, radiolabeling conditions, and the efficacy of administration methods before their initial use in clinical trials. The prospects for the use of radiolabeled ligands in cancer detection and therapy are promising because of their specificity for binding to receptors on tumor cells or tumor endothelial cells. CONCLUSIONS: Methods that increase the localization of radiolabeled ligands in solid tumors while reducing uptake in normal tissues will be required so that a sufficient radiation absorbed dose can be delivered for potentially curative treatment of radioresistant tumors in clinical radioimmunotherapy trials.