| Photodynamic therapy (PDT) is an emerging treatment for cancer and other conditions. PDT relies on the combined action of light, photosensitive drugs and molecular oxygen to generate reactive oxygen species, the most important of which is widely believed to be singlet oxygen (1O2 ). 1O2 rapidly oxidizes surrounding biomolecules in tissue, resulting in the photodynamic effect.; 1O2 is known to undergo luminescence at 1270 run, a fact that is routinely verified in simple solutions. In biological tissues, the probability of 1O2 luminescence falls to approximately 10-8 due to the dense intracellular environment and drastically reduced 1O2 lifetime. As such, measurement of 1O2 luminescence in cells in vitro or in tissues in vivo has never been reliably demonstrated in the past.; In this work, a study is presented in which 1O2 luminescence was measured for the first time during PDT of leukemia cells in vitro and normal rat tissue in vivo using a novel, near-infrared sensitive photomultiplier tube. Measurement of the kinetics of the photosensitizer and of 1O2 in these environments was also possible. Studies that demonstrate that this luminescence correlates strongly with PDT treatment response in cell suspensions and in the skin of normal mice sensitized with Amino-leveulinic acid induced protoporphyrin IX (ALA-PpIX) are also presented. These studies confirm the likely role of 1O2 in porphyrin based PDT, and are encouraging for the prospect of development of a clinical 1O2 luminescence PDT dosimetry system.; The design and experimental validation of a spatially-resolved 1O2 luminescence detection system (i.e. a 1O2 imager) is also presented, as well as a technique for determining the ground-state molecular oxygen concentration based on 1O2 kinetics. Future work includes animal tumor dose-response studies, evaluation of novel photosensitizing compounds, and design of a clinical dosimetry system. (Abstract shortened by UMI.)... |
