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

Summary 

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 24h 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 48h 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.

Abbreviations: AA, anaplastic astrocytoma, ALA, aminoluvelinic acid, BLI, bioluminescence imaging, CCD, charge coupled device, FGR, fluorescence guided resection, GBM, glioblastoma multiforme, LED, light emitting diode, MBT, malignant brain tumour, mPDT, metronomic photodynamic therapy, PpIX, protoporphyrin IX, PS, photosensitizer drug, WLR, white light resection

Keywords: Acute photodynamic therapy, Metronomic photodynamic therapy, 5-Aminoluvelinic acid, Protoporphyrin IX, Bioluminescence imaging, Glioblastoma multiforme, Malignant astrocytoma, Apoptosis, LED-fiber coupled sources