1. Optical imaging of ovarian cancer using a matrix metalloproteinase-3-sensitive near-infrared fluorescent probe
- Author
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Kuo Hwa Wang, Kuan Chou Chen, Yu Hui Tsai, Tze Chien Chen, Yung Ming Wang, Chun S. Zuo, Li Hsuan Chiu, Chun A. Changou, and Wen Fu T. Lai
- Subjects
0301 basic medicine ,Fluorescence-lifetime imaging microscopy ,endocrine system diseases ,lcsh:Medicine ,Biochemistry ,Diagnostic Radiology ,0302 clinical medicine ,Animal Cells ,Medicine and Health Sciences ,lcsh:Science ,Connective Tissue Cells ,Liquid Chromatography ,Metalloproteinase ,Multidisciplinary ,Chemistry ,Radiology and Imaging ,Chromatographic Techniques ,Proteases ,Magnetic Resonance Imaging ,female genital diseases and pregnancy complications ,Ovarian Cancer ,Enzymes ,In Vivo Imaging ,Oncology ,Connective Tissue ,030220 oncology & carcinogenesis ,Cellular Types ,Anatomy ,Preclinical imaging ,Research Article ,Stromal cell ,Imaging Techniques ,Research and Analysis Methods ,03 medical and health sciences ,In vivo ,Diagnostic Medicine ,Fluorescence Imaging ,medicine ,Cancer Detection and Diagnosis ,lcsh:R ,Cancer ,Cancers and Neoplasms ,Biology and Life Sciences ,Proteins ,Cell Biology ,medicine.disease ,High Performance Liquid Chromatography ,030104 developmental biology ,Biological Tissue ,Cancer research ,Enzymology ,Metalloproteases ,lcsh:Q ,Molecular imaging ,Stromal Cells ,Ovarian cancer ,Gynecological Tumors - Abstract
Epithelial ovarian cancer (EOC) is the seventh most common cancer among women worldwide. The 5-year survival rate for women with EOC is only 30%-50%, which is largely due to the typically late diagnosis of this condition. EOC is difficult to detect in its early stage because of its asymptomatic nature. Recently, near-infrared fluorescent (NIRF) imaging has been developed as a potential tool for detecting EOC at the molecular level. In this study, a NIRF-sensitive probe was designed to detect matrix metalloproteinase (MMP) activity in ovarian cancer cells. A cyanine fluorochrome was conjugated to the amino terminus of a peptide substrate with enzymatic specificity for MMP-3. To analyze the novel MMP-3 probe, an in vivo EOC model was established by subcutaneously implanting SKOV3 cells, a serous-type EOC cell line, in mice. This novel MMP-3-sensitive probe specifically reacted with only the active MMP-3 enzyme, resulting in a significantly enhanced NIRF emission intensity. Histological analysis demonstrated that MMP-3 expression and activity were enhanced in the stromal cells surrounding the ovarian cancer cells. These studies establish a molecular imaging reporter for diagnosing early-stage EOC. Additional studies are required to confirm the early-stage activity of MMP-3 in EOC and its diagnostic and prognostic significance.
- Published
- 2018