The sustaining of fluorescence in photodynamic diagnosis after the administration of 5-aminolevulinic acid in carcinogen-induced bladder cancer orthotopic rat model and urothelial cancer cell lines

Abstract

Background: The administration of 5-aminolevulic acid hydrochloride (5-ALA·HCl) 3 h (range: 2-4 h) before photodynamic diagnosis (PDD) is recommended for detecting bladder tumors. However, there is insufficient evidence on the time duration for the fluorescence of PDD after oral administration of 5-ALA. We investigated the sustainability of the photodynamic effect and protoporphyrinⅨ (PpⅨ) after 5-ALA administration in a carcinogen-induced bladder tumor rat model and bladder cancer cell lines.

Methods: The carcinogen-induced bladder tumor orthotopic rat model was established by the administration of N-butyl-N-(4-hydroxybutyl) nitrosamine.

Results: Red fluorescence was visible 2-8 h after the oral administration of 5-ALA in the carcinogen-induced bladder tumor rat model. Plasma and intratissue PpⅨ (nM) progressed to a higher level at 2 h and remained almost constant 2-8 h after oral administration of 5-ALA. The peak fluorescence intensity of PpⅨ was observed 3-4 h after the administration of 5-ALA in bladder cancer cell lines. The accumulated PpⅨ remained for 4 h after the removal of 5-ALA in UMUC3 cells. It was not clearly visible 3 h after the removal of 5-ALA in MGHU3 and T24 cells. The expression level of ferrochelatase was significantly lower in UMUC3 cells than in other cells. Our findings suggest that 5-ALA-assisted PDD (ALA-PDD) can aid in detecting non-muscle-invasive bladder cancer 2-8 h after 5-ALA administration.

Conclusion: Urologists might not be required to make excess effort to start ALA-PDD-assisted transurethral resection of bladder tumor after the administration of 5-ALA.

Keywords: 5-Aminolevulic acid hydrochloride; Bladder cancer; Carcinogen-induced bladder cancer orthotopic rat model; Photodynamic diagnosis; Protoporphyrin Ⅸ.