Abstract
Photodynamic therapy is a promising cancer treatment that employs wavelength-specific light in combination with a photosensitizing agent to induce local tumor destruction by photochemical generation of cytotoxic singlet oxygen. Clinical PDT has been evaluated for a variety of primary tumors, however, its use in spinal metastases to our knowledge has not been previously evaluated. A practical consideration is the ability to deliver light to bone. The investigators are evaluating a novel method of applying light to targeted spinal lesions using a minimally invasive technique similar to percutaneous vertebroplasty. This preliminary preclinical study evaluates the feasibility and efficacy of spinal PDT.
To evaluate the feasibility and efficacy of spinal meta-static photodynamic therapy (PDT) using a percutaneous minimally invasive surgical approach similar to that of vertebroplasty in a preclinical model of bone metastases.
A bioluminescent metastatic model was developed (intracardiac injection 2x106 MT-1Luc human breast cancer cells; rnu/rnu rats). In forty-three tumor bearing rats, a PDT light dose escalation trial (photosensitizer BPD-MA;2mg/Kg IV) was conducted to assess safety and efficacy of tumor ablation in a single treatment via an implanted optical fibre held adjacent to targeted spinal lesions. Pre and forty-eight hours post bioluminescent imaging was performed to gauge PDT related effects followed by post-sacrifice microCT and histology.
Spinal PDT caused a reduction in bioluminescence of targeted lesions (66% to 87% in three hour drug-light group using light fluence rates of 25J and 150J, respectively; p< 0.05). The most selective drug-light interval was twenty-four hours where PDT induced tumor cell apoptosis/necrosis occurred, however, no spinal cord injury was observed. The greatest anti-tumor effect was observed at the three hour drug-light interval but observations of neurologic sequalae (9/22 animals) highlight the importance of ongoing study to closely define the therapeutic window of PDT.
Drug dosimetry and the drug-light interval are critical in establishing an efficacious and safe treatment range for spinal PDT. Bioluminescent reporter imaging provides an in vivo longitudinal assessment of tumor growth kinetics. The feasibility of the minimally invasive approach for spinal PDT in this model has been established.
Funding: this study was support, in part, by a CBCRA (formerly CBCRI) Idea’s grant
Correspondence should be addressed to Cynthia Vezina, Communications Manager, COA, 4150-360 Ste. Catherine St. West, Westmount, QC H3Z 2Y5, Canada
