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

  • Margarete K. Akens
  • Michael R. Hardisty
  • Brian C. Wilson
  • Joerg Schwock
  • Cari M. Whyne
  • Shane Burch
  • Albert J. M. Yee
Preclinical Study

DOI: 10.1007/s10549-009-0356-7

Cite this article as:
Akens, M.K., Hardisty, M.R., Wilson, B.C. et al. Breast Cancer Res Treat (2010) 119: 325. doi:10.1007/s10549-009-0356-7

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.

Keywords

Spine Breast cancer Bone metastasis Photodynamic therapy 

Copyright information

© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  • Margarete K. Akens
    • 1
  • Michael R. Hardisty
    • 1
  • Brian C. Wilson
    • 2
  • Joerg Schwock
    • 2
  • Cari M. Whyne
    • 1
  • Shane Burch
    • 3
  • Albert J. M. Yee
    • 1
  1. 1.Division of Orthopaedic SurgerySunnybrook Health Science CentreTorontoCanada
  2. 2.Ontario Cancer InstituteTorontoCanada
  3. 3.Department of Orthopaedic SurgeryUniversity of CaliforniaSan FranciscoUSA

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