Comparing the effects of repetitive and chronic ALA mediated PDT on human glioma spheroids.

Following surgical removal of malignant brain tumors 80% of all cases develop tumor recurrence within 2 cm of the resected margin. The aim of postoperative therapy is therefore elimination of nests of tumor cells remaining in the margins of the resection cavity. However, it is unlikely that standard "one-shot" intraoperative PDT treatments can accomplish this goal. This is due mainly to the length of time required to deliver adequate light fluences to depths of 1 - 2 cm in the resection margin. Additionally, due to the short doubling time of malignant glioma cells, the kill rate per cell doubling indicates that it seems unlikely that a single relatively short treatment would be sufficient to prevent recurrence of the tumor. Multiple repetitive or chronic treatment protocols would therefore seem required. In repetitive PDT both phtosensitizer and light are given over relatively short treatment times (hours) with treatment repetition following relatively long intervals (weeks). In chronic PDT (also called metronomic), both the photosensitizer and light are delivered continuously at low rates for extended periods of time (days). The in vitro therapy response of human glioma spheroids to 5-aminolevulinic acid (ALA) mediated PDT in repetitive or chronic form were investigated. At 6J fluence, spheroid survival rates of 28 and 7% were observed for repetitive or chronic PDT protocols respectively. The results indicated that single chronic (24-48hrs) treatment) was more effective at inhibiting spheroid growth than PDT repeated at relatively long intervals (weeks) or daily fractionated PDT.