29th Annual Meeting of the American Society of Photobiology

Downtown Marriot

Chicago, Il.

Understanding the Diverse Effects of PDT Upon Tissue Oxygenation

Abstract-
The critical dependence of the photodynamic process on molecular oxygen has long focused the attention of PDT science on the status of tissue oxygenation before and during PDT treatment. As our approach towards PDT treatment delivery has evolved over the past two decades, so has our understanding of the fundamentally important effects this treatment delivery has on tissue oxygenation. For example, our early treatment regimes for preclinical (murine) and clinical tumor therapy generally called for high doses of the photosensitizer Photofrin (15 mg/kg and 2 mg/kg, respectively). These conditions, upon light activation, have well defined, dramatic effects on the tissue vasculature, blood flow and consequently on oxygenation. It is now known that superimposed on these effects is the acute depletion of oxygen via photochemical oxygen consumption, a process that is highly dependent on photosensitizer type and concentration, as well as fluence rate. How profoundly these parameters affect oxygen availability for the photodynamic process has been demonstrated both preclinically and in patients. In recent years, PDT has moved towards lower photosensitizer doses, photosensitizers that have milder vascular effects, and/or new light delivery regimes (lower fluence rates or intermittent illumination). This shift in treatment parameters alters the dynamic interplay between the different components of the PDT response, direct photodynamic cell kill, vascular tumor damage and, probably, the inflammatory response. Examples illustrating the complexities of the oxygen question in PDT will be presented, and possible implications for clinical treatment outcome will be discussed. The work presented is supported by NIH grants RO1 CA42278, PO1 CA55791 and P30 CA16056.

Keywords: photodynamic therapy, oxygen