SINGLET OXYGEN-MEDIATED VERSUS NONSINGLET OXYGEN-MEDIATED MECHANISMS OF SENSITIZER PHOTOBLEACHING AND THEIR EFFECTS ON PHOTODYNAMIC DOSIMETRY

We report the effects of singlet oxygen (O-1(2)) and non-O-1(2)-mediat ed sensitizer photobleaching on oxygen consumption and dosimetry durin g photodynamic therapy (PDT) of sensitized multicell tumor spheroids, We develop a theoretical model for the description of non-O-1(2)-media ted photobleaching resulting from irreversible reactions of the excite d singlet or triplet sensitizer populations with cell substrate. We sh ow that the fluence-dependent simple exponential decay expression of s ensitizer degradation is not consistent with these mechanisms and, the refore, with any reasonable mechanism that we consider, because we hav e shown previously that O-1(2)-mediated photobleaching cannot be descr ibed by a simple exponential with a constant photobleaching coefficien t (I. Georgakoudi et al,, Photochem, Photobiol, 65, 135-144, 1997), An alysis of oxygen microelectrode measurements performed at the edge of Nile blue selenium (EtNBSe)- and protoporphyrin IX (PpIX)-sensitized s pheroids during PDT demonstrates that the former drug photobleaches vi a a non-O-1(2)-mediated mechanism, while the latter is degraded via a O-1(2)-mediated mechanism. Comparisons of the cytotoxic effects of EtN BSe,vith those of Photofrin(R) (a drug that is degraded via a O-1(2)-m ediated mechanism) indicate that the lower threshold O-1(2) dose and t he higher extinction coefficient and O-1(2) yield for EtNBSe do not ne cessarily result in improved photodynamic effects, thus emphasizing th e importance of the sensitizer photobleaching mechanism for dosimetry.