In vivo fluence rate and fractionation effects on tumor response and photobleaching: Photodynamic therapy with two photosensitizers in an orthotopic rat tumor model

The effect of fluence rate and light fractionation on phototoxicity was inv estigated in vivo in an orthotopic rat bladder tumor model. Two photosensit izers, benzoporphyrin derivative monoacid ring A and 5-aminoevulinic acid-i nduced protoporphyrin IX, were studied. For a given cumulative light dose o f 30 J/cm(2), enhanced tumor destruction was observed from both photosensit izers when using either lower fluence rates or fractionated light delivery. Photobleaching experiments in vivo demonstrated that the photobleaching ra te, however, was not fluence rate dependent. The fluence rate and light fra ctionation effects on tumor phototoxicity lead to rapid local depletion in oxygen concentration that inhibited subsequent photochemical reactions nece ssary for efficient photodestruction of tumor cells. Nicotinamide did not e nhance photodynamic therapy efficacy, suggesting that the added increase of oxygen within the tumor was not sufficient to enhance photodestruction of hypoxic cell fractions. The independence of the photobleaching rate with fl uence rate suggests distinct mechanisms, at least in part, of photodestruct ion of the tumor and the photosensitizer and that the rate of photosensitiz er photobleaching may not always be an appropriate monitor for singlet oxyg en availability and photodynamic therapy dosimetry.