THE MECHANISM OF PHOTOFRIN(R) PHOTOBLEACHING AND ITS CONSEQUENCES FORPHOTODYNAMIC DOSIMETRY

We report experimental results that support a theory of self-sensitize d singlet oxygen-mediated bleaching of the porphyrin photosensitizer P hotofrin(R). Microelectrode measurements of photodynamic oxygen consum ption were made near the surface of individual, Photofrin-sensitized E MT6 spheroids during laser irradiation. The progressive decrease in ph otochemical oxygen consumption with sustained irradiation is consisten t with a theory in which bleaching occurs via self-sensitized singlet oxygen reaction with the photosensitizer ground state. A bleaching mod el based solely on absorbed optical energy density is inconsistent wit h the data. Photobleaching has a significant effect on calculated phot odynamic dose distributions in 500 mu m diameter spheriods. Dose distr ibutions corrected for the effects of bleaching produce a new estimate (12.1 +/- 1.2 mM) for the threshold dose of reacting singlet oxygen i n this system.