FLUORESCENCE PHOTOBLEACHING OF ALA-INDUCED PROTOPORPHYRIN-IX DURING PHOTODYNAMIC THERAPY OF NORMAL HAIRLESS MOUSE SKIN - THE EFFECT OF LIGHT DOSE AND IRRADIANCE AND THE RESULTING BIOLOGICAL EFFECT

The photobleaching of 5-aminolaevulinic acid (ALA)-induced protoporphy rin IX (PpIX) was investigated during superficial photodynamic therapy (PDT) in normal skin of the SKH HR1 hairless mouse, The effects of li ght dose and fluence rate on the dynamics and magnitude of photobleach ing and on the corresponding PDT-induced damage were examined. The res ults show that the PDT damage cannot be predicted by the total light d ose, Photobleaching was monitored over a wide range of initial PpIX fl uorescence intensities, The rate of PpIX photobleaching is not a simpl e function of fluence rate but is dependent on the initial concentrati on of sensitizer. Also, at high fluence rates (50-150 mW/cm(2), 514 nm ) oxygen depletion is shown to have a significant effect. The rate of photobleaching with respect to light dose and the corresponding PDT da mage both increase with decreasing fluence rate. We therefore suggest that the definition of a bleaching dose as the fight dose that causes a 1/e reduction in fluorescence signal is insufficient to describe the dynamics of photobleaching and PDT-induced damage, We have detected t he formation of PpIX photoproducts during the initial period of irradi ation that were themselves subsequently photobleached. In the absence of oxygen, PpIX and its photoproducts are not photobleached. We presen t a method of calculating a therapeutic dose delivered during superfic ial PDT that demonstrates a strong correlation with PDT damage.