A pre-clinical (rnu/rnu rat) vertebral metastasis model of osteolytic (MT-1 breast cancer) was optimized and used to evaluate the effect of vertebral PDT. PDT alone and in combination with other standard local (radiation therapy, RT) and systemic (bisphosphonates, BP) therapies was evaluated through bioluminescence imaging, micro-CT based stereology, histology, and biomechanical testing. Single PDT treatment (photosensitizer BPD-MA, 690nm light) ablated tumor tissue in targeted vertebrae. PDT led to significant increases in bone structural properties, with greatest benefits observed from combined BP+PDT therapy: 76% and 19% increases in bone volume fraction in treated tumor-bearing and healthy untreated controls, respectively. Similar synergistic improvements (but of lesser magnitude) were found in combined PDT+RT treatments.
The safety and feasibility of MIS+PDT were evaluated in scale-up animal studies, refining surgical technique for clinical translation. Following appropriate institutional review board as well as Health Canada approval, 5 patients (light only control group) have undergone protocoled treatment to date. These patients have guided further refinement of human therapeutic application from a laser delivery and vertebral bone access perspective.