THE POTENTIAL OF RADIOLABELED EGF-DEXTRAN CONJUGATES IN THE TREATMENTOF URINARY-BLADDER CARCINOMA

BACKGROUND. Muscle-invasive urothelial carcinoma of the urinary bladde r has a poor prognosis in spite of available therapies. These tumors f requently overexpress the epidermal growth factor receptor (EGFr), a p ossible target for therapeutic conjugates. The aim of this study was t o construct an EGF-carbohydrate conjugate that would be potentially us eful for both local (i.e., intravesical) and systemic radiotherapy. ME THODS. EGF was coupled to periodate activated dextran by reductive ami nation. Receptor binding tests in vitro were conducted, using the huma n urothelial carcinoma cell line RT4 and the human malignant glioma ce ll line U-343-MG as a positive control. In the in vivo experiments, nu de mice with subcutaneously grown xenografts of the RT4 tumor were inj ected intravenously with technetium-99m-labeled EGF conjugates. Sample s of organs, blood, and tumors were collected after 24 hours. The radi oactive uptake was calculated as a percentage of the dose per gram of tissue. RESULTS. The specific binding in the in vitro experiment was 9 0-95%. The binding was similar in both cell lines. There was a positiv e uptake in the tumors in the in vivo experiment, with tumor-to-blood ratios from 2:1 to 6:1. The uptake level in the kidneys was similar to that in the tumors (i.e., similar to 0.05% dose per gram of tissue). The other organs had a lower uptake compared with the tumor uptake. CO NCLUSIONS. The results indicate that radiolabeled EGF-dextran has the potential to become a tool for local treatment of recurrent bladder ca rcinoma. With appropriate modifications, it should be possible to use this conjugate for systemic radio-therapy as well. (C) 1997 American C ancer Society.