Radioimmunotherapy of human bladder cancer in a nude mouse model comparing Bi-213-anti-EGFR-MAb and Th-226-anti-EGFR-MAb

Objectives Transurethral resection of urothelial cancer still results in high recurrence rates. In new concepts for therapy of disseminated tumor cells α-emitter immunoconjugates are applied. Therefore the aim of this study was to compare the therapeutic efficacy of Bi-213- and Th-226-anti-EGFR-MAb in an orthotopic EGFR-overexpressing bladder carcinoma model.

Methods 2x10⁶ luciferase transfected EJ28 cancer cells were instilled into the bladders of female swiss nu/nu mice following urothelial electrocautery. 10 tumor-bearing mice each were intravesically instilled with 0.925 MBq of Bi-213-MAb or 0.37 MBq Th-226-MAb 1h, 7d and 14d after cell inoculation; controls received PBS. Tumor development and therapy response was imaged via bioluminescence imaging and survival observed up to 300d.

Results Mice of the control group reached a median survival of 41d. Bi-213-anti-EGFR therapy prolonged survival >300 d in 90%, 80% and 40% of animals treated 1h, 7d and 14d after cell instillation, respectively. Therapy with Th-226-MAb starting 10/2008 turned out to be as effective as Bi-213 therapy: 90% of animals of each group treated 1h, 7d and 14 d after cell inoculation are still alive without signs of toxicity.

Conclusions Both α-emitter-anti-EGFR conjugates effectively eradicated disseminated tumor cells.Thus, therapy using Th-226-anti-EGFR might be a very promising supplement and/or alternative to Bi-213-anti-EGFR in treatment of urothelial cancer.