CHAPTER 19: Pre-Clinical Models for Glioma Photodynamic Therapy

The efficacy of photodynamic therapy (PDT) for the treatment of primary and recurrent gliomas has been evaluated in a fair number of clinical trials over the past two decades. While some studies showed an effect, it is evident that PDT as a standalone or adjuvant to standard therapy has highly variable efficacy and bears morbidity risks for some patients, preventing its broader adoption in the clinic. Cofactors as causes for the observed efficacy variance and strategies to improve PDT efficacy need to be determined in preclinical models, and the same applies to dosimetry concepts and response monitoring strategies. However, the use of small murine models poses in itself challenges for PDT research, such as the intracranial dimensions between the tumor and eloquent areas of the brain being small compared to the light and hence PDT dose gradient. Here, we present current work pertaining to the use of preclinical models for the PDT-mediated destruction of gliomas, including the biological relevance of commonly used glioma cell lines, the means to modify protoporphyrin IX (PpIX) synthesis in vivo and the tissue responsivity to PpIX-mediated intracranial PDT, as well as novel magnetic resonance imaging-based approaches for predicting tissue response. Employing the appropriate preclinical models has the potential for rapid hypothesis generation and testing in order to design improved clinical studies in the future that will be needed for demonstrating improved efficacy in the vast majority of patient if PDT is to become a first-line therapy in neurosurgery.