Hexvix ® mediated rat bladder photodynamic therapy: The impact of fluence rate on normal bladder preservation

Abstract

Bladder PDT, the first FDA indication, has been abandoned in favour of photodiagnosis with ALA or derivatives. Major drawback of this treatment modality is prolonged and severe irritative bladder symptoms, due to lack of selectivity of the drug and generalized urothelial necrosis. Low fluence rates are known to potentiate therapeutic efficacy due to an oxygen sparing regime. We have evaluated the effect of low fluence rate PDT on therapeutic outcome and side effects in rat tumor bearing bladders. Bladders were instilled with 8 mM hexylaminolevulinate and illuminated with 635 nm light to a total light dose of 20 or 15 J/cm2 at 100 or 15 mW/cm2, 5 rats per group. Fluence rates of 15 mW/cm2 did not provoke enhancement of cardiac and respiratory rhythms as opposed to 100 mW/cm2, neither was hematuria observed post treatment. Macroscopic aspects of bladders at 100 mW/cm2 show thickened bladders with hemorrhagic areas whereas 15 J/cm2 does not alter macroscopic features. Pathology revealed the absence of viable superficial tumors, irrespective of irradiation conditions. Inflammatory volume was calculated to be 96 a.u. for high fluence high light dose, reduced to 18 a.u. when reducing the light dose and 12 a.u. for the low fluence rates, irrespective of the light dose. Normal urothelial is preserved over the total bladder in case of 15 mW/cm2, whereas major portions of the bladder show absence of reduction of cell layers at 100 mW/cm2. Low fluence rate PDT does not hamper therapeutic efficacy and minimizes local side effects in rats.