title: Preclinical evaluation of copper-67 labelled anti-MUC1 mucin antibody C595 for therapeutic use in bladder cancer.
abstract: Transitional cell carcinoma of the bladder is the fifth commonest cause of death from cancer in men in the United Kingdom. Most patients present early with superficial disease, though with current treatment up to 20% progress to invasive disease, which has a poor prognosis. Better local treatments are required to limit this tumour progression. The ease of access to the bladder via a catheter provides the ideal opportunity for antibody (Ab) targeted therapy. We have previously shown that indium-111 labelled anti-MUC1 mucin Ab C595 selectively localises to bladder tumours after intravesical administration. We have selected copper-67 as an alternative radiolabel with suitable physical characteristics for radioimmunotherapy. This communication demonstrates that C595 can be reproducibly labelled with 67Cu and that the radioimmunoconjugate is both stable and maintains high immunoreactivity. Pilot studies on cystectomy specimens in a novel ex vivo system and in one patient confirmed the ability of this conjugate to localise to tumour after intravesical administration. On the basis of these studies we are now in a position to study the intravesical administration of 67Cu-labelled C595 in patients with bladder cancer with a view to a therapeutic trial.
authors.affiliation: Department of Urology, City Hospital, Nottingham, UK.
authors.forename: O D
authors.initials: OD
authors.lastname: Hughes
authors.forename: M C
authors.initials: MC
authors.lastname: Bishop
authors.forename: A C
authors.initials: AC
authors.lastname: Perkins
authors.forename: M
authors.initials: M
authors.lastname: Frier
authors.forename: M R
authors.initials: MR
authors.lastname: Price
authors.forename: G
authors.initials: G
authors.lastname: Denton
authors.forename: A
authors.initials: A
authors.lastname: Smith
authors.forename: R
authors.initials: R
authors.lastname: Rutherford
authors.forename: P A
authors.initials: PA
authors.lastname: Schubiger
mesh_terms: D000283:Administration, Intravesical; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D002295:Carcinoma, Transitional Cell / Q000000981:diagnostic imaging / Q000532:radiotherapy*; D003301:Copper Radioisotopes / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D018396:Mucin-1 / Q000276:immunology*; D010865:Pilot Projects; D016719:Radioimmunodetection; D016499:Radioimmunotherapy; D001749:Urinary Bladder Neoplasms / Q000000981:diagnostic imaging / Q000532:radiotherapy*
chemical_list: D000911:Antibodies, Monoclonal; D003301:Copper Radioisotopes; D018396:Mucin-1