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Targeting of bladder cancer with monoclonal antibody NCRC48—a possible approach for intravesical therapy

1995; Wiley; Volume: 76; Issue: 1 Linguagem: Inglês

10.1111/j.1464-410x.1995.tb07837.x

1365-2176

R. Kunkler, M.C. Bishop, D.J. Green, M. V. Pimm, M.R. Price, M. Frier,

Peptidase Inhibition and Analysis

Objective To determine the localization of the anti‐MUCl mucin monoclonal antibody (mAb) NCRC48 to bladder cancer following intravesical administration. Patients and methods mAb NCRC48 (330–500 μg) radiolabeled 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 uro‐thelium (expressed as the percentage of the instilled dose/g × 10 3 ± SD) at 2h 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.