Bi-213-anti-EGFR-cetuximab(Technische Universitat Munchen)

Female Swiss nu/nu mice were intravesically inoculated with luciferase-transfected EJ28 human bladder carcinoma cells after the induction of urothelial lesions by electrocautery. At different time points after cell inoculation, mice were treated intravesically with (213)Bi-anti-EGFR-mAb, mitomycin C, or unlabeled anti-EGFR-mAb. Tumor development and therapeutic response were evaluated via bioluminescence imaging.

Mice without therapy and those treated with unlabeled anti-EGFR-mAb reached a median survival of 41 d and 89 d, respectively. Mice that underwent therapy with 0.925 MBq of (213)Bi-anti-EGFR-mAb 1 h, 7 d, or 14 d after cell instillation survived more than 300 d in 90%, 80%, and 40% of the cases, respectively. Therapy with 0.37 MBq 1 h or 7 d after tumor cell inoculation resulted in survival of more than 300 d in 90% and 50% of mice, respectively. Mitomycin C treatment after 1 h and 7 d prolonged survival to more than 300 d in 40% and 50%, respectively; however, treatment turned out to be nephrotoxic. In contrast, no signs of nephrotoxicity could be observed after (213)Bi-anti-EGFR-mAb treatment.

The study suggests that radioimmunotherapy using intravesically instilled (213)Bi-anti-EGFR-mAb is a promising option for treatment of bladder cancer in patients.