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

• 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. • 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. • 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. • 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.