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Journal of Nuclear Medicine Vol. 50 No. 10 1700-1708
© 2009 by Society of Nuclear Medicine
doi: 10.2967/jnumed.109.065961

Basic Science Investigation

Intravesical {alpha}-Radioimmunotherapy with 213Bi-Anti-EGFR-mAb Defeats Human Bladder Carcinoma in Xenografted Nude Mice

Birgit Pfost1, Christof Seidl1, Michael Autenrieth2, Dieter Saur3, Frank Bruchertseifer4, Alfred Morgenstern4, Markus Schwaiger1 and Reingard Senekowitsch-Schmidtke1

1 Department of Nuclear Medicine, Technische Universität München, Munich, Germany; 2 Department of Urology, Technische Universität München, Munich, Germany; 3 Department of Internal Medicine II, Technische Universität München, Munich, Germany; and 4 European Commission, Joint Research Centre, Institute for Transuranium Elements, Karlsruhe, Germany

Correspondence: For correspondence or reprints contact: Reingard Senekowitsch-Schmidtke, Department of Nuclear Medicine, Technische Universität München, Ismaninger Strasse 22, 81675 Munich, Germany. E-mail: senekowitsch{at}lrz.tum.de

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 {alpha}-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.

Key Words: {alpha}-emitter 213Bi • bladder cancer • locoregional therapy • orthotopic mouse model • bioluminescence imaging

COPYRIGHT © 2009 by the Society of Nuclear Medicine, Inc.


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