Photodynamic therapy of diseased bone

摘要

Objective: Photodynamic therapy (PDT) defines the oxygen-dependent reaction that occurs upon light-mediated activation of a photosensitizing compound, culminating in the generation of cytotoxic, reactive oxygen species, predominantly, singlet oxygen. We are investigating PDT treatment of diseased bone. Methods: Using a rat model of human breast cancer (MT-1)-derived bone metastasis we confirmed the efficacy of benzoporphyrin-derivative monoacid (BPD-MA)-PDT for treating metastatic lesions within vertebrae or long bones. Results: Light administration (150 J) 15 mins after BPD-MA (2.5 mg/Kg, i.v.) into the lumbar (L3) vertebra of rats resulted in complete ablation of the tumour and surrounding bone marrow 48 hrs post-PDT without paralysis. Porcine vertebrae provided a model comparable to that of human for light propagation (at 150 J/cm) and PDT response (BPD-MA; 6 mg/m~2, i.v.) in non-tumour vertebrae. Precise fibre placement was afforded by 3-D cone beam computed tomography. Average penetration depth of light was 0.16 ± 0.04 cm, however, the necrotic/non-necrotic interface extended 0.6 cm out from the treatment fiber with an average incident fluence rate of 4.3 mW/cm~2. Non-necrotic tissue damage was evident 2 cm out from the treatment fiber. Current studies involving BPD-MA-PDT treatment of primary osteosarcomas in the forelimbs of dogs are very promising. Magnetic resonance imaging 24 hr post treatment reveal well circumscribed margins of treatment that encompass the entire 3-4 cm lesion. Finally, we are also interested in using 5-aminolevulinic acid (ALA) mediated PDT to treat osteomyelitis. Response to therapy was monitored as changes in bioluminescence signal of staphylococcus aureus (SA)-derived biofilms grown onto 0.5 cm lengths of wire and subjected to ALA-PDT either in vitro or in vivo upon implant into the intramedullary space of rat tibia. Transcutaneous delivery of PDT (75 J/cm~2) effectively eradicated SA-biofilms within bone. Conclusions: Results support the application of PDT to the treatment of primary or metastatic lesions within bone. Secondly, that ALA-PDT may be useful as a treatment for osteomyelitis. Further studies aim to optimize the parameters of delivering PDT into bone and explore imaging technologies that can be used for clinical PDT.