The Mechanism of Photofrin® Photobleaching and Its Consequences for Photodynamic Dosimetry

Abstract

We report experimental results that support a theory of self-sensitized singlet oxygen-mediated bleaching of the porphyrin photosensitizer Photofrin®. Microelectrode measurements of photodynamic oxygen consumption were made near the surface of individual, Photofrinsensitized EMT6 spheroids during laser irradiation. The progressive decrease in photochemical oxygen consumption with sustained irradiation is consistent with a theory in which bleaching occurs via self-sensitized singlet oxygen reaction with the photosensitizer ground state. A bleaching model based solely on absorbed optical energy density is inconsistent with the data. Photobleaching has a significant effect on calculated photodynamic dose distributions in 500 μm diameter spheriods. Dose distributions corrected for the effects of bleaching produce a new estimate (12.1 ± 1.2 mM) for the threshold dose of reacting singlet oxygen in this system.