ALA-mediated photodynamic therapy of experimental malignant glioma in the BD-IX rat model

Introduction: Failure of treatment for high grade gliomas is usually due to local recurrence at the site of surgical resec-tion indicating that a more aggressive form of local therapy could be of benefit. Photodynamic therapy (PDT) is a local form of treatment involving the administration of a tumor-localizing photosensitizing drug that is activated by light of a specific wavelength The results of in vitro experiments indicated that PDT, given at low fluence rates was substantially more effective at inhibiting glioma spheroid growth than short term high fluence rate regimes. This prompted the initia-tion of in vivo studies of low fluence rate 5-aminolevulinic acid (ALA) PDT in a rat glioma model. Methods:BT4C cell line tumors were established in the brains of inbred BD- IX rats. Eighteen days following tumor induction the animals were injected with 125 mg/kg ALA ip. and four hours later light treatment at various fluences and fluence rates were given after the introduction of an optical fiber. Tumor histology and animal survival were examined. Results: In vitro experiments verified that the cell line was sensitive to ALA PDT. Microfluorometry of frozen tissue sections showed that PpIX is produced with a greater than 20:1 tumor to normal tissue selectivity ratio four hours after ALA injection. Histological examination demonstrated neutrophil infiltration and tumor central necrosis in low fluence rate treated tumors. Conclusions: Low fluence rate long term ALA mediated PDT had a more pronounced effect on tumor histology than single shot short duration treatments at similar total fluence levels.