IN VITRO FLUENCE RATE EFFECTS IN PHOTODYNAMIC REACTIONS WITH AlPcS₄ AS SENSITIZER

Anne C.E. Moor^1,2, Johan W.M. Lagerberg¹, Karmi Tijssen¹, Sarah Foley³, T. George Truscott³, Irene E. Kochevar⁴, Anneke Brand², Tom M.A.R. Dubbelman¹, and John VanSteveninck¹

1) Dept. of Molecular Cell Biology, Leiden University, Leiden, the Netherlands

2) Dept. of Immunohematology and Bloodbank, Leiden University Hospital, Leiden, the Netherlands

3) Dept. of Chemistry, Keele University, Keele, Staffs., ST5 5BG, UK

4) Wellman Laboratories of Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA

This study was supported by The Praeventiefonds, the Netherlands, Grant no. 28-2414 and the E.E.C. PDT EURONET, Grant no. ERBCHRXCT930178.

ABSTRACT

It has been shown previously that the efficiency of photodynamic therapy both in vivo and in vitro is dependent on fluence rate. In this study, different in vitro experiments showed that tetrasulfonated aluminum phthalocyanine is more efficient in photosensitization if the light is delivered at low fluence rate. Erythrocyte damage, virus inactivation and photooxidation of reduced glutathione 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 explanation for the observed fluence rate effects might be found in different reaction pathways, which 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, since a change in fluence rate, even with similar total fluences, might influence photobiological results in an unexpected way.