The aim of this thesis was to further optimize RIT for RCC using radiolabeled mAb cG250. A series of parameters that could improve the efficacy of RIT were studied in patients and animal models. The performance of two forms of the cG250 antibody (IgG versus F(ab')2 fragments) has been studied. Furthermore, the most effective radionuclide for cG250-based RIT was determined, and the safety and efficacy of two cycles of RIT were established in neprectomized patients with stage IV disease. In addition, we aimed to assess an additive effect between RIT and immunotherapy with the cytokines IL-2, IF-alpha and IFN-gamma. Finally, the excellent targeting characteristics of cG250 for the detection of RCC metastases with PET were explored (immuno-PET), and also the potential of [18F]FDG-PET to visualize RCC lesions.