DOSE-DEPENDENT DESTRUCTION OF HUMAN GASTROINTESTINAL NEOPLASMS BY PHOTODYNAMIC THERAPY - A QUANTITATIVE PILOT-STUDY IN ATHYMIC NUDE-MICE

Background: Photodynamic therapy (PDT) appears to be a promising method for the local treatment of malignant tumors. However, little data are available concerning the relationship between administered energy density and photosensitizer concentration with respect to the degree of tumor destruction. The present study was designed to evaluate this functional relationship in an in vivo tumor model with human gastrointestinal carcinomas. Methods: Sixteen different human gastrointestinal tumors (two esophageal, five gastric, five colonic and four rectal), heterotransplanted into nude mice (NMRI - nu/nu), were treated either with different energy densities between 25 and 300 J/cm2 at a constant sensitizer dose of 9 mg/kg or, alternatively, treated with different sensitizer dosages of 1.5 to 9 mg/kg at a constant energy density of 150 J/cm2. Photosan containing the enriched active component dihematoporphyrinether (DHE) was used as a photosensitizer. Tumor necrosis was semiquantitatively measured by light microscopy. Results: All tumors underwent tissue necrosis following PDT. When the drug dose was kept constant, the amount of tumor necrosis varied according to the applied energy density. For esophageal, gastric (150-300 J/cm2) and colorectal cancers (75-100 J/cm2), we were able to establish different threshold values for tumor necrosis greater-than-or-equal-to 90%. When the energy density was kept constant, tumor necrosis increased as a function of the administered drug dose. Different threshold values for tumor necrosis greater-than-or-equal-to 90% were determined for gastric (>9 mg/kg), esophageal and colorectal (4.5 mg/kg) cancers with respect to the photosensitizer dose. Reciprocity of the applied photosensitizer and energy dose values could not be determined. Conclusions: We conclude that human gastrointestinal carcinomas transplanted into nude mice exhibit different reactions to PDT. Both the photosensitizer dose and the energy density influence the extent of tumor necrosis. Our study shows that the prevailing clinical dosimetry for gastrointestinal tumors may result in inadequate treatment by under- or overdosing of the applied energy density or photosensitizer dose, the two most important treatment parameters in PDT.