Standard treatment regimens consisting of surgery, radiation and chemotherapy have proven ineffective for the treatment of high-grade gliomas such as glioblastoma multiforme (GBM). An effective cure requires elimination of nests of tumor cells that have migrated from the resection margin and infiltrated normal brain. A number of localized therapies, including light-based approaches such as photodynamic therapy (PDT) and photochemical internalization (PCI) are currently under investigation for the management of GBM patients.
Several studies have demonstrated a high degree of synergy between PDT and bleomycin, via the PCI mechanism, in a variety of in vitro and in vivo models, including glioma cell lines. The purpose of this study was to examine the efficacy of combined treatments consisting of PDT and the chemotherapeutic agent, 5-fluorouracil (5-FU) in a 3-dimensional spheroid model consisting of F98 rat glioma cells. Spheroids were incubated with a photosensitizer (aluminum phthalocyanine disulfonate; AlPcS2a) and irradiated with 670 nm laser light. Three different wash protocols (0, 4 and 24 h) were employed to determine whether any observed interactions between PDT and 5-FU could be attributed to the PCI mechanism, or were simply due to different cytotoxic pathways of the two treatment modalities.
Although the combined PDT + 5-FU treatments resulted in greater suppression of spheroid growth compared to either treatment alone, no statistically significant differences in growth effects were observed between 0 and 4 h wash protocols suggesting that the combined treatment effects were due to different mechanisms of cytotoxicity, rather than a PCI effect
