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|Title:||Intravesical a-Radioimmunotherapy with 213Bi-Anti-EGFR-mAb Defeats Human Bladder Carcinoma in Xenografted Nude Mice|
|Authors:||PFOST Birgit; SEIDI Christof; AUTENRIETH Michael; SAUR Dieter; BRUCHERTSEIFER Frank; MORGENSTERN Alfred; SCHWAIGER Markus; SENEKOWITSCH-SCHMIDTKE Reingard|
|Citation:||JOURNAL OF NUCLEAR MEDICINE vol. 50 no. 10 p. 1700-1708|
|Publisher:||SOC NUCLEAR MEDICINE INC|
|Type:||Articles in Journals|
|Abstract:||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 EGFR-overexpressing bladder carcinoma cell line EJ28 and to compare therapeutic efficacy of intravesically instilled alpha-particle emitting 213Bi-anti-EGFR-MAb with mitomycin C. Methods: Female swiss nu/nu mice were intravesically inoculated with luciferase transfected EJ28 human bladder carcinoma cells following 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 imaged 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 >300 d in 90%, 80% and 40% of cases, respectively. Therapy with 0.37 MBq 1 h or 7 d after tumor cell inoculation resulted in survival >300 d in 90% and 50% of mice, respectively. Mitomycin C treatment after 1 h and 7 d prolonged survival >300 d in 40% and 50%, respectively, however turned out to be nephrotoxic. In contrast, no signs of nephrotoxicity could be observed following 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.|
|JRC Institute:||Institute for Transuranium Elements|
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