How to avoid local side effects of bladder photodynamic therapy: impact of the fluence rate.
OBJECTIVE
We studied how to avoid irritative bladder symptoms after bladder photodynamic therapy, such as urgency, frequency and pain, which are associated with the inflammation and destruction of normal urothelium.


METHODS
Rats bearing orthotopic bladder tumors were instilled with hexyl-aminolevulinate and illuminated with red light at a high vs low (100 vs 15 mW/cm(2)) fluence rate. Cystectomy specimens 48 hours after treatment were subjected to anatomopathological examination. Inflammatory reaction and apoptosis were evaluated. In vivo photobleaching was assessed during illumination at each fluence rate.


RESULTS
All superficial tumors were eradicated irrespective of light dose and fluence rate. High fluence rates induced necrosis with inflammatory reaction and absent normal urothelium. Low fluence rates did not provoke inflammation and resulted in apoptotic cell death with preserved urothelial integrity. This could be attributable to faster photobleaching of the photosensitizer in normal urothelium at low fluence rates.


CONCLUSIONS
Bladder photodynamic therapy at a low fluence rate minimizes side effects without hampering therapeutic efficacy.
Université de Lorraine, Centre de Recherche en Automatique de Nancy, Unité Mixtes de Recherche 7039, Vandœuvre-lès Nancy Cedex, France.
Aurélie
A
François
Aurélie
A
Salvadori
Aude
A
Bressenot
Lina
L
Bezdetnaya
François
F
Guillemin
Marie Ange
MA
D'Hallewin
D000622:Aminolevulinic Acid / Q000009:adverse effects / Q000031:analogs & derivatives*; D000818:Animals; D017209:Apoptosis; D015653:Cystectomy; D005260:Female; D007124:Immunoenzyme Techniques; D010778:Photochemotherapy / Q000009:adverse effects*; D017319:Photosensitizing Agents / Q000009:adverse effects*; D051381:Rats; D011916:Rats, Inbred F344; D013050:Spectrometry, Fluorescence; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000601:surgery
D017319:Photosensitizing Agents; D000622:Aminolevulinic Acid; C419924:5-aminolevulinic acid hexyl ester
5-aminolevulinic acid hexyl ester; ALA; CIS; PBS; PDT; PpIX; aminolevulinic acid; carcinoma in situ; complications; k; m/v; mass per volume; phosphate buffered saline; photobleaching constant; photochemotherapy; photodynamic therapy; protoporphyrin IX; urinary bladder; urinary bladder neoplasms