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Proceedings Paper

Photodynamic therapy of diseased bone
Author(s): Stuart K. Bisland; Albert Yee; Jeffery Siewerdsen; Brian C. Wilson; Shane Burch
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Paper Abstract

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 BPDMA (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/m2, 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/cm2. 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/cm2) effectively eradicated SAbiofilms 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.

Paper Details

Date Published: 27 August 2005
PDF: 11 pages
Proc. SPIE 5863, Therapeutic Laser Applications and Laser-Tissue Interactions II, 58630U (27 August 2005); doi: 10.1117/12.633091
Show Author Affiliations
Stuart K. Bisland, Ontario Cancer Institute, University Health Network, Univ. of Toronto (Canada)
Albert Yee, Sunnybrook and Women's College Health Sciences Ctr. (Canada)
Jeffery Siewerdsen, Ontario Cancer Institute, University Health Network, Univ. of Toronto (Canada)
Brian C. Wilson, Ontario Cancer Institute, University Health Network, Univ. of Toronto (Canada)
Shane Burch, Ontario Cancer Institute, University Health Network, Univ. of Toronto (Canada)


Published in SPIE Proceedings Vol. 5863:
Therapeutic Laser Applications and Laser-Tissue Interactions II
Hubert van den Bergh; Alfred Vogel, Editor(s)

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