title: Use of fluorescein isothiocyanate-human serum albumin for the intravesical photodiagnosis of non-muscle-invasive bladder cancer: an in vitro study using multicellular spheroids composed of normal human urothelial and urothelial cell carcinoma cell lines.
abstract: OBJECTIVE
  • To evaluate human serum albumin (HSA), fluorescently labelled with fluorescein isothiocyanate (FITC), as a potential intravesical photodiagnostic method for the early detection of non-muscle-invasive bladder cancer.
  
  
  METHODS
  • By using multicellular spheroids prepared from normal human urothelial (NHU) cells and from different urothelial cell carcinoma (UCC) cell lines (T24, J82), we simulated three-dimensionally the normal urothelium and non-muscle-invasive UCCs present in the bladder of patients. • The distribution of FITC-HSA in these spheroids was investigated.
  
  
  RESULTS
  • Our data showed that fluorescently labelled albumin is quite evenly dispersed throughout the spheroids. However, in the case of the 10 mg/mL incubations, the fluorescence intensity seems to increase slightly towards the spheroid core. • Using 1 mg/mL, the penetration of FITC-HSA in T24 differed significantly from the penetration in NHU spheroids, but this was not the case for J82 spheroids. • When the concentration of FITC-HSA was increased 10-fold, all UCC spheroids exhibited a significantly different accumulation of FITC-HSA.
  
  
  CONCLUSIONS
  • As spheroids represent a suitable in vitro model for predicting the in vivo behaviour of compounds, our data suggest that FITC-HSA could be used for the early detection of non-muscle-invasive bladder cancer. • Human serum albumin conjugates of new or already available intravesical drugs could be generated to create alternative bladder cancer therapies with increased selectivity.
authors.affiliation: Pharmaceutical Biology Laboratory, Catholic University of Leuven, Leuven, Belgium.
authors.forename: Mieke
authors.initials: M
authors.lastname: Roelants
authors.forename: Ben
authors.initials: B
authors.lastname: Van Cleynenbreugel
authors.forename: Hendrik
authors.initials: H
authors.lastname: Van Poppel
authors.forename: Evelyne
authors.initials: E
authors.lastname: Lerut
authors.forename: Peter A M
authors.initials: PA
authors.lastname: de Witte
mesh_terms: D002295:Carcinoma, Transitional Cell / Q000175:diagnosis*; D045744:Cell Line, Tumor; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives*; D005456:Fluorescent Dyes; D006801:Humans; D007150:Immunohistochemistry; D053554:Keratin-20 / Q000378:metabolism; D010784:Photomicrography / Q000379:methods*; D012709:Serum Albumin; D018874:Spheroids, Cellular / Q000473:pathology; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis*; D019459:Urothelium / Q000166:cytology
chemical_list: C518288:FITC-albumin; D005456:Fluorescent Dyes; D053554:Keratin-20; D012709:Serum Albumin; D016650:Fluorescein-5-isothiocyanate