TARGETING OF BLADDER-CANCER WITH MONOCLONAL-ANTIBODY NCRC48 - A POSSIBLE APPROACH FOR INTRAVESICAL THERAPY

Objective To determine the localization of the anti-MUC1 mucin monoclonal antibody (mAb) NCRC48 to bladder cancer following intravesical. administration. Patients and methods mAb NCRC48 (330-500 mu G) radiolabelled with (111)indium (11-17 MBq) was administered intravesically to 12 unselected patients with radiological evidence of bladder cancer. Tumour localization was assessed by gamma-camera imaging and by tissue biodistribution studies on biopsies obtained at cystoscopy at about 2 or 24 h after the procedure. After 24 h, whole blood radioactivity was measured and 3 weeks after the procedure the serum level of human anti-mouse antibodies was estimated using an ELISA method. Results Eleven patients had tumours confirmed at cystoscopy (grades 1-3, stages pTa-pT2). The mean uptake of NCRC48 by tumour and by normal urothelium (expressed as the percentage of the instilled dose/gx10(3)+/-SD) at 2 h was 3.42+/-3.68 and 0.41+/-0.77 (P<0.05). After 24 h, the values for tumour and normal urothelium were 1.17+/-1.18 and 0.17+/-0.11, respectively. Areas of increased activity on the scintigrams were consistent with the position of the tumours at cystoscopy. No radioactivity was detected in blood at 24 h and there was no evidence of a human anti-mouse antibody response. Conclusion The MUC1 mucin may be a suitable antigen to-study the potential of therapeutic strategies based on monoclonal antibody targeting of superficial bladder cancer and may allow the development of more effective agents in the treatment of this condition.