Abstract

Photodynamic therapy is a potential treatment for superficial bladder cancer that utilizes photosensitizer drugs, which are activated by light to cause tissue destruction. However, first-generation photosensitizers cause prolonged phototoxicity, have poor tumour specificity and can accumulate within detrusor muscle, resulting in permanent loss of bladder capacity following treatment. A newer drug, called 5-aminolaevulinic acid (ALA), generates a sensitizer called protoporphyrin IX (PpIX) in situ and has been shown, qualitatively, to be more tumour specific. The fluorescence kinetics of ALA-induced PpIX was investigated in patient biopsies of bladder tumour, normal urothelium and detrusor muscle, both in vitro after incubation of specimens in ALA-rich culture medium for various times and in vivo after instillation of intravesical ALA before endoscopic resection. The fluorescence in tumour tissue was twice that of normal urothelium in vitro and up to tenfold in vivo. There was little ALA-induced fluorescence in detrusor muscle, both in vitro and in vivo. Most importantly, no patients experienced phototoxicity or other adverse events following intravesical instillation of ALA.

Highlights

  • Incubation of tissue samples in aminolaevulinic acid (ALA) resulted in an initial timedependent increase in tissue fluorescence for all three tissue ty pes over the first 2-6 h

  • Tumour fluorescence appeared to peak between 2 and 6 h of incubation in ALA. but. by 24 h. this had diminished to fluorescence levels similar to those of normal urothelium and detrusor muscle (Ficure 1)

  • Areas of poorly defined dysplasia and carcinoma in situ do not. . necessarilv need to be precisely defined for effective photodynamic therapy to take place

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Summary

Objectives

The purpose of this study was to determine. The fluorescence kinetics of ALA-induced PplX in human TCC. Compared with normal urothelium and detrusor muscle in vitro

Results
Discussion
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