Interstitial in vivo ALA-PpIX mediated metronomic photodynamic therapy (mPDT) using the CNS-1 astrocytoma with bioluminescence monitoring

Background: We report the first truly metronomic delivery of photodynamic therapy using the rat-derived CNS-1 astrocytoma, a model with close histopathology with human brain tumours. Methods: Metronomic PDT (mPDT) was delivered to CNS-1 bearing female Lewis rats. 5-Aminoluvelinic acid was delivered continuously through drinking water, while light was delivered via tetherless, light-weight, LED-based fiber coupled optical sources. Tumour burden before and after mPDT treatment was determined using bioluminescence imaging (BLI). Results: Preliminary studies demonstrated that 24 h of continuous mPDT illumination was capable of destroying small tumours (7 days post-implant). The reduction or elimination of tumour was confirmed using BLI and corroborated by histology. Additional studies showed that 24 and 48 h continuous mPDT illumination had the capability to delay tumour re-growth by a period corresponding to approximately two doubling times. Animals given 4-day mPDT did not show any signs of tumour re-growth via BLI at 26 days post-tumour implantation. Conclusions: In summary, these results demonstrate the feasibility of delivering mPDT for extended periods, as well as its potential as a treatment for small brain tumours. (C) 2007 Elsevier B.V. All rights reserved.