Therapeutic efficacy of intravesical -radioimmunotherapy with Bi-213-anti-EGFR-MAb in a human bladder cancer nude mouse model

Abstract

Objectives: Due to a high recurrence rate after transurethral resection of urothelial cancer new therapeutic strategies are urgently needed. The aim of this study was to establish an orthotopic human bladder cancer mouse model using an EGFR-overexpressing cancer cell line and to compare the therapeutic efficacy of intravesically instilled Bi-213-anti-EGFR-MAb with Mitomycin C. Methods: Female swiss nu/nu mice were catheterized and urothelial lesions were set by electrocautery. 2x106 luciferase transfected EJ28 cells were inoculated intravesically in 7 groups of 10 mice each. 1h, 7d and 14d after cancer cell inoculation 0.925 MBq of Bi-213-MAb were instilled into the bladder. 2 groups received 40µg Mitomycin C at 1h and 7d, 1 group received unconjugated MAb, the control only PBS. Tumor development and therapy response were imaged by bioluminescence imaging and survival observed up to 300d. Results: Mice of the control group and those treated with the unconjugated MAb reached a median survival of 41d and 69d, respectively. Mice that underwent Bi-213-MAb therapy 1h, 7d and 14d after cell instillation survived >300d in 90%, 80% and 40%, respectively. Mitomycin C treatment after 1h and 7d resulted in a survival >300d in 40% and 50%, respectively. Conclusions: Intravesically instilled Bi-213-MAb significantly prolonged survival without toxicity whereas Mitomycin C induced nephrotoxicity. Thus, therapy using Bi-213-anti-EGFR-MAb is a very promising approach to reduce the high recurrence rate of urothelial carcinoma.JRC.E.5-Nuclear chemistr