TY - JOUR
T1 - Imaging of specific activation of photodynamic molecular beacons in breast cancer vertebral metastases
AU - Liu, Tracy W.
AU - Akens, Margarete K.
AU - Chen, Juan
AU - Wise-Milestone, Lisa
AU - Wilson, Brian C.
AU - Zheng, Gang
PY - 2011/6/15
Y1 - 2011/6/15
N2 - 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 (PPMMPB), 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 PPMMPB in MT-1 cells. Using a clinically relevant metastatic model, fluorescent imaging establishes the specific activation of PPMMPB 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 MMPBs can specifically image breast cancer vertebral metastases, thereby differentiating tumor and healthy tissue.
AB - 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 (PPMMPB), 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 PPMMPB in MT-1 cells. Using a clinically relevant metastatic model, fluorescent imaging establishes the specific activation of PPMMPB 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 MMPBs can specifically image breast cancer vertebral metastases, thereby differentiating tumor and healthy tissue.
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U2 - 10.1021/bc200169x
DO - 10.1021/bc200169x
M3 - Article
C2 - 21585206
AN - SCOPUS:79959240365
SN - 1043-1802
VL - 22
SP - 1021
EP - 1030
JO - Bioconjugate Chemistry
JF - Bioconjugate Chemistry
IS - 6
ER -