Photodynamic therapy of newly implanted glioma cells in the rat brain

Abstract

Background and Objective: A syngeneic rat brain tumor model is used to investigate the effects of aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT) on small clusters of tumor cells sequestered in normal brain. Study Design/Materials and Methods: Biodistribution studies on tumor-bearing animals were undertaken in order to determine the occurrence of photosensitizer in tumor cells invading normal brain. ALA-PDT toxicity in normal brain and gross tumor were evaluated from histopathology. Effects of PDT on isolated glioma cells in normal brain were investigated by treating animals 48 hours after tumor cell implantation. Results: Fluorescence microscopy of frozen tissue sections showed that photosensitizer content was limited and variable in tumor tissue invading normal brain. ALA-PDT with high light doses resulted in significant damage to both gross tumor and normal brain, however, the treatment failed to prolong survival of animals with newly implanted glioma cells. In contrast, animals inoculated with tumor cells pre-incubated in vitro with ALA showed a significant survival advantage in response to PDT. Conclusion: The results show that ALA-PDT could not prevent tumors from forming if treatment was performed shortly after tumor initiation. This was likely due to inadequate levels of ALA/PpIX in the glioma cells. © 2006 Wiley-Liss, Inc.