Project 172190

Photodynamic Therapy (PDT) attained approval for various oncological indications, but only for applications in the skin or other superficial tumours such as the bladder. Particular treatments of solid tissue volumes do not approach the clinically surgical precision to afford a survival advantage superior to surgery, so its minimal invasive nature has benefits over surgery and other oncological treatment modalities. This failure of PDT to live up to its potential also in solid tumors is related to two separate but equally important reasons. The first is of physical nature and relates to the ability to shape the therapy to the tumour, whereas the second is of biological nature and relates to the intrinsic high sensitivity of various normal tissues to PDT despite a selective accumulation of the photosensitizer in the highly proliferating malignant tissue. This proposal will further the potential of PDT for solid tissues by developing physics based strategies to improve conformal therapy and the use of a adjuvant pharmaceutical to reduce the sensitivity of normal tissues to PDT. We made advances in shaping therapy planning using light diffusers with custom made emission profile. Here, we proposed to use numerical calculation and phantom measurements to first determine the optimum position of light fluence rate sensors to quantify the optical properties within the CTV and monitor them throughout PDT. As gains for regular shaped clinical target volumes, such as the prostate, will be limited we will orient ourselves additionally towards head and neck cancer, the possibly most difficult indications. Erythropoietin (EPO) and other neuroprotective agents are under investigation in stroke or trauma of brain. The EPO receptor (EPOR) is expressed in normal neuron and glial cells and commonly lacking in brain tumor. Hence, upregulation of EPOR in brain prior to PDT, followed by EPO administration prior and after PDT has potential to reduce sensitivity of normal brain.