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

Objective To determine the localization of the anti-MUC1 mucin monoclo nal antibody (mAb) NCRC48 to bladder cancer following intravesical. ad ministration. Patients and methods mAb NCRC48 (330-500 mu G) radiolabe lled with (111)indium (11-17 MBq) was administered intravesically to 1 2 unselected patients with radiological evidence of bladder cancer. Tu mour localization was assessed by gamma-camera imaging and by tissue b iodistribution studies on biopsies obtained at cystoscopy at about 2 o r 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-p T2). The mean uptake of NCRC48 by tumour and by normal urothelium (exp ressed as the percentage of the instilled dose/gx10(3)+/-SD) at 2 h wa s 3.42+/-3.68 and 0.41+/-0.77 (P<0.05). After 24 h, the values for tum our and normal urothelium were 1.17+/-1.18 and 0.17+/-0.11, respective ly. Areas of increased activity on the scintigrams were consistent wit h the position of the tumours at cystoscopy. No radioactivity was dete cted 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 dev elopment of more effective agents in the treatment of this condition.