Production and characterisation of a C595 antibody-99mTc conjugate for immunoscintigraphy of bladder cancer.
Current radiological techniques for staging bladder cancer are inaccurate, especially in the identification of pelvic lymph node metastases. Immunoscintigraphy has the potential to offer improved staging for bladder cancer. The aim of this study was to label the anti-MUC1 monoclonal antibody C595 with 99mtechnetium (Tc), the most widely used diagnostic radionuclide, and assess the potential of the resultant conjugate for intravenous immunoscintigraphy of bladder cancer. A direct, reduction-mediated technique was used to label the antibody. The resultant conjugate was shown to be highly immunoreactive, stable and bound specifically to MUC1. The ability of the conjugate to bind to bladder tumours was demonstrated in an ex vivo model where the mean tumour:normal urothelial uptake was 5.7:1 and by intravesical administration in patients with bladder cancer where the mean tumour:normal urothelial uptake was 20.4:1. The ability of the conjugate to localise MUC1-expressing tumours was demonstrated in a nude mouse xenograft model. A conjugate of 99mTc-C595 has been produced and characterised, and it may be suitable for intravenous immunoscintigraphy, a potential novel staging tool for bladder cancer.
Simms
M S
MS
Department of Urology, Nottingham City Hospital, Hucknall Road, Nottingham NG5 1PB, UK. msimms@gertrude42.freeserve.co.uk
Murray
A
A
Denton
G
G
Scholfield
D P
DP
Price
M R
MR
Perkins
A C
AC
Bishop
M C
MC
D000818:Animals; D000911:Antibodies, Monoclonal; D002850:Chromatography, Gel; D006801:Humans; D008207:Lymphatic Metastasis / Q000000981:diagnostic imaging / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D018396:Mucin-1 / Q000276:immunology; D009367:Neoplasm Staging / Q000379:methods; D009368:Neoplasm Transplantation; D010446:Peptide Fragments / Q000276:immunology; D016719:Radioimmunodetection / Q000379:methods*; D013667:Technetium; D001749:Urinary Bladder Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology
D000911:Antibodies, Monoclonal; C116055:MUC1 tandem repeat peptide; D018396:Mucin-1; D010446:Peptide Fragments; D013667:Technetium