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Defining the therapeutic window of vertebral photodynamic therapy in a murine pre-clinical model of breast cancer metastasis using the photosensitizer BPD-MA (Verteporfin).

Abstract
Breast cancer is known to cause metastatic lesions in the bone, which can lead to skeletal-related events. Currently, radiation therapy and surgery are the treatment of choice, but the success rate varies and additional adjuncts are desirable. Photodynamic therapy (PDT) has been applied successfully as a non-radiative treatment for numerous cancers. Earlier work has shown that the athymic rat model is suitable to investigate the effect of PDT on bone metastasis and benzoporphyrin-derivative monoacid ring A (BPD-MA; verteporfin) has been shown to be a selective photosensitizer. The aim of this study was to define the therapeutic window of photosensitizer with regard to drug and light dose. Human breast carcinoma cells (MT-1)-stable transfected with the luciferase gene-were injected intra-cardiacally into athymic rats. At 14 days, the largest vertebral lesion by bioluminescence imaging was targeted for single treatment PDT. A drug escalating-de-escalating scheme was used (starting drug dose and light energy of 0.2 mg/kg and 50 J, respectively). Outcomes included 48 h post-treatment bioluminescence of remaining viable tumour, histomorphometric assessment of tumour burden, and neurologic evaluation. The region of effect by bioluminescence and histology increased with increasing drug dose and light energy. A safe and effective drug-light dose combination in this model appears to be 0.5 mg/kg BPD-MA and applied light energy of less than 50 J for the thoracic spine and 1.0 mg/kg and 75 J for the lumbar spine. For translation to clinical use, it is an advantage that BPD-MA (verteporfin), a second-generation photosensitizer, is already approved to treat age-related macular degeneration. Overall, PDT represents an exciting potential new minimally-invasive local, safe and effective therapy in the management of patients with spinal metastases.
AuthorsMargarete K Akens, Michael R Hardisty, Brian C Wilson, Joerg Schwock, Cari M Whyne, Shane Burch, Albert J M Yee
JournalBreast cancer research and treatment (Breast Cancer Res Treat) Vol. 119 Issue 2 Pg. 325-33 (Jan 2010) ISSN: 1573-7217 [Electronic] Netherlands
PMID19263216 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Photosensitizing Agents
  • Porphyrins
  • verteporfin
  • Luciferases
Topics
  • Animals
  • Breast Neoplasms (genetics, pathology)
  • Cell Line, Tumor
  • Dose-Response Relationship, Drug
  • Dose-Response Relationship, Radiation
  • Female
  • Genes, Reporter
  • Humans
  • Luciferases (genetics)
  • Lumbar Vertebrae (drug effects, pathology)
  • Mice
  • Photochemotherapy (methods)
  • Photosensitizing Agents (pharmacology)
  • Porphyrins (pharmacology)
  • Rats
  • Rats, Nude
  • Spinal Neoplasms (drug therapy, genetics, secondary)
  • Thoracic Vertebrae (drug effects, pathology)
  • Time Factors
  • Transfection
  • Xenograft Model Antitumor Assays

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