Treatment of Bladder Cancer with Bi-213-anti-EGFR Immunoconjugates in a Nude Mouse Model

Abstract

Therapy of non-muscle-invasive bladder cancer (carcinoma in situ) comprises transurethral resection of the tumor and subsequent instillation of the chemotherapeutic drug mitomycin C in order to eradicate remaining tumor cells. Yet 15 – 40% of treated patients relapse within 5 years. Therefore, new therapeutic strategies to combat tumor recurrence are needed. Alpha-particle emitting radionuclides efficiently kill single tumor cells or small tumor cell clusters. Because the epidermal growth factor receptor (EGFR) is overexpressed on bladder cancer cells conjugates composed of the alpha-emitter Bi-213 and the anti-EGFR antibody matuzumab should provide a powerful drug to eliminate disseminated bladder cancer cells. Therefore, the aims of our study were (i) to analyse the cytotoxic effects of Bi-213-anti-EGFR radioimmunoconjugates at the cellular level, (ii) to evaluate therapeutic efficacy of intravesically applied Bi-213-anti-EGFR-Mab in a nude mouse model with intravesical human bladder cancer xenografts, (iii) to compare Bi-213-anti-EGFR-Mab efficacy with chemotherapy using mitomycin C and (iv) to demonstrate that radioimmunotherapy does not damage the bladder wall.JRC.E.5-Nuclear chemistr