PROCEEDINGS ARTICLE | July 13, 2009
Proc. SPIE. 7380, Photodynamic Therapy: Back to the Future
KEYWORDS: Light sources, Photodynamic therapy, Tissues, Magnetic resonance imaging, Spectroscopy, Luminescence, Silver, Semiconductor lasers, Tissue optics, Brain
A summary of clinical trials employing photodynamic diagnosis (PDD) and photodynamic therapy (PDT) for
the diagnosis and treatment of brain malignancies is presented. Intra-cavity PDT has been performed within
the surgical cavity following FGR, employing oral administration of 5-aminolevulinic acid (5-ALA), either targeting
fluorescing tissue regions that were not removed during FGR due to safety reasons (referred to as focal
PDT, n=20) or illuminating the entire resection cavity (referred to as integral PDT, n=9). Both approaches
proved technically feasible and safe. Spectroscopic measurements performed pre-, during and post-PDT revealed
Protoporphyrin IX (PpIX)-photobleaching of more than 95% after the delivery of 200 J/cm2. This light dose
did not induce any side effects. Furthermore, interstitial PDT (iPDT) has been employed within one feasibility
trial (n=10) and one Phase I/II trial (n=15). Here, three to six cylindrical light diffusors (20-30 mm length,
200 mW/cm, 720 J/cm) were positioned within the target tissue under stereotactic guidance. Pre-treatment
planning was performed with the intent to target the entire tumour volume with a sufficient light dose while
also minimising the risk of any light-induced temperature increase. For the feasibility trial patients with small,
recurrent gliomas were included, resulting in a median survival of 15 months as well as some unexpected longterm
survivals (up to 5 years). The Phase I/II trial employed the same clinical procedures. Here, the 12-month
survival was 35% and the median progression-free survival was 6 months. In summary, stereotactic iPDT in
combination with treatment-planning could be shown to be a safe and feasible treatment modality. These trials
are presently being extended to also include on-line monitoring of PpIX fluorescence and photobleaching kinetics.
Preliminary data has revealed dramatically different PpIX levels and photobleaching kinetics. Such data
could possibly be employed for realtime treatment monitoring and as an early prognostic marker for the PDT
response.
