Optimization of photodynamic therapy: the influence of photosensitizer uptake and distribution on tumor response

PDT is being used to treat small localized cancer or as an adjuvant to debulking surgery for more advanced disease. Clinical protocols for PDT are based on the assumption that optimum intervals between photosensitizer administration and illumination are at times of maximum differential between drug retention in tumor and surrounding normal tissue. Tumor destructing can, however, occur either by direct cell killing or by vascular mediated damage. The aim of this study was to investigate the relationship between plasma and tumor photosensitizer levels and PDT effect for the RIF1 murine tumor and the H-MESO1 xenograft tumor. mTHPC plasma levels decreased rapidly according to a biexponential fit. The tumor drug levels, however increased from 5 minutes to 6 hours after injection and remained high for at least 48 hours. Maximum tumor PDT response was seen at 1 to 3 hour drug-light intervals with very little effect for drug-light intervals > 24 hours. No correlation was found between tumor mthpc levels and tumor response, whereas plasma mTHPC levels and PDT correlated significantly. These studies support the hypothesis that vascular mediated damage is more important than direct tumor cell toxicity and that it is drug exposure of endothelial cells in vessels feeding the tumor which determines PDT response.© (2001) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.