Photodynamic therapy of vertebral metastases: evaluating tumor-to-neural tissue uptake of BPD-MA and ALA-PpIX in a murine model of metastatic human breast carcinoma.
Photodynamic therapy has been successfully applied to numerous cancers. Its potential to treat cancer metastases in the spine has been demonstrated previously in a preclinical animal model. The aim of this study was to test two photosensitizers, benzoporphyrin-derivative monoacid ring A (BPD-MA) and by 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX), for their potential use to treat bony metastases. The difference in photosensitizer concentration in the spinal cord and the surrounding tumor-bearing vertebrae was of particular interest to assess the risk of potential collateral damage to the spinal cord. Vertebral metastases in a rat model were generated by intracardiac injection of human breast cancer cells. When tumor growth was confirmed, photosensitizers were injected systemically and the animals were euthanized at different time points. The following tissues were harvested: liver, kidney, ovaries, appendicular bone, spinal cord and lumbar vertebrae. Photosensitizer tissue concentration of BPD-MA or PpIX was determined by fluorescence spectrophotometry. In contrast to BPD-MA, ALA-PpIX did not demonstrate an appreciable difference in the uptake ratio in tumor-bearing vertebrae compared to spinal cord. The highest ratio for BPD-MA concentration was found 15 min after injection, which can be recommended for therapy in this model.
Akens
Margarete K
MK
Division of Orthopaedic Surgery, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada. makens@uhnres.utoronto.ca
Yee
Albert J M
AJ
Wilson
Brian C
BC
Burch
Shane
S
Johnson
Crystal L
CL
Lilge
Lothar
L
Bisland
Stuart K
SK
D000622:Aminolevulinic Acid / Q000627:therapeutic use*; D000818:Animals; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000556:secondary; D001943:Breast Neoplasms / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D010778:Photochemotherapy; D011166:Porphyrins / Q000627:therapeutic use*; D011524:Protoporphyrins / Q000627:therapeutic use*; D051381:Rats; D011923:Rats, Nude; D000077362:Verteporfin
D011166:Porphyrins; D011524:Protoporphyrins; D000077362:Verteporfin; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX