In vitro Fluence Rate Effects in Photodynamic Reactions with AIPcS₄ as Sensitizer

Abstract

It has been shown previously that the efficiency of photodynamic therapy (PDT) both in vivo and in vitro is dependent on fluence rate. In this study, different in vitro experiments showed that tetrasulfonated aluminum phthalocyanine (AIPcS4) is more efficient in photosensitization if the light is delivered at low fluence rate. Erythrocyte damage, virus inactivation and photooxidation of reduced glutathione (GSH) and histidine were all enhanced if light was delivered at 100 W/m2 as compared to 500 W/m2. Bleaching did not occur under these conditions. Oxygen depletion, shown to be important in fluence rate effects observed in vivo, does not seem to be involved. On theoretical grounds saturation of the triplet state is not likely under these conditions. A possible explantation for the observed fluence rate effects might be found in different reaction pathways, that are favored under high or low fluence rate illuminations. These reactions might involve uni- or bimolecular reactions of intermediate products, resulting in less efficiency at higher fluence rate. It proves to be important, under all circumstances, to monitor fluence rate, because a change in fluence rate, even with similar total fluences, might influence photobiological results in an unexpected way.

Photodynamic therapy of newly implanted glioma cells in the rat brain

“…Of particular importance is the observation that PDT-induced cytotoxicity is critically dependent on both radiant exposure and the rate of light delivery (irradiance)-lower irradiances are more effective, especially at low radiant exposures. The decreased efficacy of higher irradiances observed in BT 4 C monolayers is in good agreement with the findings of other investigators using a variety of cell lines and photosensitizers [25,26]. Oxygen depletion, which has been shown to be important in fluence rate effects observed in vivo, is likely not involved.…”

“…Oxygen depletion, which has been shown to be important in fluence rate effects observed in vivo, is likely not involved. The observed effect may be due to different mechanisms operating under high and low fluence rates, involving oxidizing intermediates [25]. The data presented in Figure 1 give a good estimate of the light delivery conditions required for optimum PDT effect in this cell line, and therefore provide a good starting point for further study in animals.…”

Platelets, photosensitizers, and PDT

“…Similar results were obtained with an electron microscopic and serological analysis of the platelets derived from HpD treated normal mice showed that platelet necrosis proceeds rapidly with almost all platelets were necrotized after 8 h. Even directly after irradiation some platelets exhibited swelling and deformation [68]. Similarly, PDT-related erythrocyte damage has been shown to be light-dependent [69].…”

Intracellular Photobleaching of 5,10,15,20-Tetrakis(m-hydroxyphenyl) chlorin (Foscan®) Exhibits a Complex Dependence on Oxygen Level and Fluence Rate¶

“…Another in vitro study examining the effect of lower fluence rate excitation, using a phthalocyanine sensitizer, has found that damage was enhanced at lower fluence rates (53). In that work it was also proposed that different mechanisms operate under low and high fluence rates, involving oxidizing intermediates.…”