title: Imaging of specific activation of photodynamic molecular beacons in breast cancer vertebral metastases.
abstract: Breast cancer is the second leading cause of cancer-related death in women. Approximately 85% of patients with advanced cases will develop spinal metastases. The vertebral column is the most common site of breast cancer metastases, where overexpression of matrix metalloproteinases (MMPs) promotes the spread of cancer. Current therapies have significant limitations due to the high associated risk of damaging the spinal cord. An attractive alternative is photodynamic therapy providing noninvasive and site-selective treatment. However, current photosensitizers are limited by their nonspecific accumulation. Photodynamic molecular beacons (PP(MMP)B), activated by MMPs, offer another level of PDT selectivity and image-guidance preserving criticial tissues, specifically the spinal cord. Metastatic human breast carcinoma cells, MT-1, were used to model the metastatic behavior of spinal lesions. In vitro and in vivo evidence demonstrates MMP specific activation of PP(MMP)B in MT-1 cells. Using a clinically relevant metastatic model, fluorescent imaging establishes the specific activation of PP(MMP)B by vertebral metastases versus normal tissue (i.e., spinal cord) demonstrating the specificity of these beacons. Here, we validate that the metastasis-selective mechanism of PP(MMP)Bs can specifically image breast cancer vertebral metastases, thereby differentiating tumor and healthy tissue.
authors.affiliation: Department of Medical Biophysics, University of Toronto, Canada.
authors.forename: Tracy W
authors.initials: TW
authors.lastname: Liu
authors.forename: Margarete K
authors.initials: MK
authors.lastname: Akens
authors.forename: Juan
authors.initials: J
authors.lastname: Chen
authors.forename: Lisa
authors.initials: L
authors.lastname: Wise-Milestone
authors.forename: Brian C
authors.initials: BC
authors.lastname: Wilson
authors.forename: Gang
authors.initials: G
authors.lastname: Zheng
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D020782:Matrix Metalloproteinases / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D008954:Models, Biological; D057054:Molecular Imaging; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D013125:Spinal Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000556:secondary*; D023041:Xenograft Model Antitumor Assays
chemical_list: D017319:Photosensitizing Agents; D020782:Matrix Metalloproteinases