RT Journal Article SR Electronic T1 Intravesical α-Radioimmunotherapy with 213Bi-Anti-EGFR-mAb Defeats Human Bladder Carcinoma in Xenografted Nude Mice JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 1700 OP 1708 DO 10.2967/jnumed.109.065961 VO 50 IS 10 A1 Birgit Pfost A1 Christof Seidl A1 Michael Autenrieth A1 Dieter Saur A1 Frank Bruchertseifer A1 Alfred Morgenstern A1 Markus Schwaiger A1 Reingard Senekowitsch-Schmidtke YR 2009 UL http://jnm.snmjournals.org/content/50/10/1700.abstract AB Transurethral resection of urothelial carcinoma often results in tumor recurrence due to disseminated tumor cells. Therefore, new therapeutic strategies are urgently needed. The aim of this study was to establish an orthotopic human bladder carcinoma mouse model using the epidermal growth factor receptor (EGFR)–overexpressing bladder carcinoma cell line EJ28 and to compare therapeutic efficacy of intravesically instilled α-particle–emitting 213Bi-anti-EGFR-monoclonal antibody (mAb) with mitomycin C. Methods: 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 213Bi-anti-EGFR-mAb, mitomycin C, or unlabeled anti-EGFR-mAb. Tumor development and therapeutic response were evaluated via bioluminescence imaging. Results: 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 213Bi-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 213Bi-anti-EGFR-mAb treatment. Conclusion: The study suggests that radioimmunotherapy using intravesically instilled 213Bi-anti-EGFR-mAb is a promising option for treatment of bladder cancer in patients.