SPATIAL MEASUREMENT OF OXYGEN LEVELS DURING PHOTODYNAMIC THERAPY USING TIME-RESOLVED OPTICAL SPECTROSCOPY

Tissue oxygenation is one of the key dosimetric factors involved in th e application of photodynamic therapy (PDT). However, quantitative stu dies of oxygenation levels at and surrounding the treatment site have been lacking both before, during and after treatment. With the recent development of sensitive, non-invasive, optical spectroscopic techniqu es based on oxygen-dependent phosphorescence quenching of probe compou nds, oxygenation levels can now be measured quantitatively at selected sites with spatial resolution on the millimeter scale. We present res ults using the phosphorescent compound, palladium meso-tetra( carboxyp henyl) porphine, for measurement of in vivo microvascular oxygen tensi ons in rat liver during PDT. Time-resolved phosphorescence detection w as carried out using fibre-optic sensoring, and oxygen tensions were d etermined from the phosphorescence lifetimes using Stern-Volmer analys is. During PDT treatment using 5-aminolaevulinic (ALA) acid-induced pr otoporphyrin IX (PPIX) with a 50 mg/kg ALA dose, oxygen levels near th e irradiation fibre placed on the surface of the liver showed a signif icant decrease by a factor of ten from 20 to 2 torr after an energy do se of 60 J using 100 mW at 635 nm. Areas farther from the treatment si te which were exposed to lower light doses exhibited lower reductions in oxygen levels. This spectroscopic technique is a highly sensitive m eans of investigating tissue oxygenation during and after treatment, a nd should help not only to advance the understanding of hypoxia and mi crovascular damage in the PDT mechanism but also contribute to improvi ng the dosimetry of PDT. (C) 1998 Elsevier Science S.A. All rights res erved.