Photodynamic therapy for the treatment of vertebral metastases in a rat model of human breast carcinoma.
The feasibility and efficacy of photodynamic therapy (PDT) for the treatment of vertebral metastases using a minimally invasive surgical technique adapted from vertebroplasty was evaluated in a rodent model. Initial validation included photosensitizer (benzoporphyrin-derivative monoacid-ring A) drug uptake studies and in vitro confirmation of PDT efficacy. Intracardiac injection of human MT-1 breast cancer cells was performed in athymic rats. In 63 rats that developed vertebral metastases 21 days post-inoculation, single treatment of PDT was performed using a parapedicular approach placing an optical fiber adjacent to targeted vertebrae. Two milligrams per kilogram of photosensitizer drug was administered intravenously followed by 150 mW of 690 nm light illumination at varying drug-light intervals and light energies. Histologic and immunohistochemical analysis was performed assessing treatment effect. Local tumor viability and growth was quantified by bioluminescence imaging pre and 48 h post-treatment. PDT demonstrated an ablative effect on vertebral metastases (light energies 25-150 J). The effect varied in proportion to light energy with the greatest anti-tumor effect observed at 150 J using a 3 h drug-light interval. 9/22 rodents in the 3 h drug-light interval developed hindlimb paralysis following treatment, consistent with drug uptake studies demonstrating an increase in spinal cord uptake 3h following drug administration. The observations of paralysis following treatment highlight the importance of closely defining the therapeutic window of treatment in safety and efficacy.
Burch
S
S
The Spine Program, Division of Orthopaedic Surgery, Sunnybrook and Women's College Health Sciences Centre, University of Toronto, Ontario, Canada M4N 3M5.
Bisland
S K
SK
Bogaards
A
A
Yee
A J M
AJ
Whyne
C M
CM
Finkelstein
J A
JA
Wilson
B C
BC
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008163:Luminescent Measurements; D008325:Mammary Neoplasms, Experimental / Q000473:pathology*; D009368:Neoplasm Transplantation; D008517:Phytotherapy; D051381:Rats; D013125:Spinal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary*; D014183:Transplantation, Heterologous