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Scientific article
English

Analysis of differential PDT effect in rat bladder tumor models according to concentrations of intravesical hexyl-aminolevulinate

Published inPhotochemical & photobiological sciences, vol. 7, no. 9, p. 1018-1024
Publication date2008
Abstract

The hexylester of 5-aminolevulinic acid (HAL) is a very efficient precursor of the photosensitizer protoporphyrin IX (PpIX) for photodynamic therapy (PDT). Our previous study, performed in rat orthotopic bladder tumors, indicated an opposite effect of HAL/PpIX-PDT according to HAL concentration. The present study investigated possible reasons for this differential effect considering the impact of extracted amounts of PpIX in normal and tumor bearing bladders along with PpIX distribution in distinctive histopathological layers. High performance liquid chromatography (HPLC) analysis of tumor and normal bladder tissues after 8 mM and 16 mM HAL instillation showed that PpIX was the main porphyrin species. The PpIX production in tumor bladders instilled with 8 mM HAL was significantly higher than after 16 mM HAL. Fluorescence confocal microscopy demonstrated a punctuate bright fluorescence pattern in tumor zones of bladders instilled with 8 mM HAL, whereas a more diffuse cytoplasmatic fluorescence distribution was observed after 16 mM HAL instillation. Immunofluorescence staining together with transmission electron microscopy showed severe mitochondrial damage in tumor zones of bladders treated with 8 mM HAL/PpIX PDT, with intact mitochondria in tumor zones of bladders treated with 16 mM HAL/PpIX PDT. We conclude that the differential response to HAL/PpIX PDT in function of HAL concentrations could be attributed to diminished PpIX synthesis and differential intracellular localisation of PpIX. Mitochondria were shown to be the critical photodamaged sites of HAL/PpIX PDT and as such tissue sensitivity to treatment can be estimated through investigation of intracellular PpIX distribution.

Keywords
  • Aminolevulinic Acid/analogs & derivatives/therapeutic use
  • Animals
  • Cell Line, Tumor
  • Chromatography, High Pressure Liquid
  • Disease Models, Animal
  • Female
  • Microscopy, Electron, Transmission
  • Photochemotherapy
  • Photosensitizing Agents/metabolism/therapeutic use
  • Protoporphyrins/metabolism/therapeutic use
  • Rats
  • Rats, Inbred F344
  • Urinary Bladder Neoplasms/pathology/therapy/ultrastructure
Citation (ISO format)
BERRAHMOUNE, Saoussen et al. Analysis of differential PDT effect in rat bladder tumor models according to concentrations of intravesical hexyl-aminolevulinate. In: Photochemical & photobiological sciences, 2008, vol. 7, n° 9, p. 1018–1024. doi: 10.1039/b804921a
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Article (Published version)
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ISSN of the journal1474-905X
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