Lai Wen-Fu T, Chang Chung-Hsun, Tang Yi, Bronson Roederick, Tung Ching-Hsuan
Center for Molecular Imaging Research, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.
Osteoarthritis Cartilage. 2004 Mar;12(3):239-44. doi: 10.1016/j.joca.2003.11.005.
Osteoarthritis is currently diagnosed utilizing X-ray and MRI-techniques, both of which are based on the morphological changes of tissue. However, once changes are detected, the tissue has an irreversible defect. This study investigates early diagnosis of OA on a molecular basis using a recently developed cathepsin B sensitive near-infrared (NIR) fluorescent probe.
Twelve male nude mice were induced osteoarthritis by intra-articular injection of collagenase (1.0%, w/v) into the right knee joint. The left knee joint served as the negative control. The cathepsin B NIR probe is activated by arthritis-associated cathepsin B, thus resulting in the emission of an intensive NIR fluorescence signal which can be detected in vivo. NIR fluorescence signals were acquired on an optical imaging system using an excitation wavelength of 610-650 nm and an emission wavelength of 680-720 nm.
Mild to moderate degenerative cartilage was observed 1 month after collagenase injection. NIR fluorescence imaging of mice showed approximately a 3-fold difference in signal intensity between osteoarthritic and normal joints 24 h after intravenous injection of the reporter probe. Immunohistochemical evaluation also revealed cathepsin B expression in the arthritic lesion of femorotibial joints, and not in the control contra-lateral knee joints.
As the cathepsin B activatable NIR fluorescent imaging showed a significant difference between the osteoarthritic and normal joints, the cathepsin B activatable NIR fluorescent probe thus offers a potential new imaging technology for early OA diagnosis.
骨关节炎目前通过X射线和MRI技术进行诊断,这两种技术均基于组织的形态学变化。然而,一旦检测到变化,组织就会出现不可逆的缺陷。本研究使用最近开发的组织蛋白酶B敏感近红外(NIR)荧光探针,在分子水平上研究骨关节炎的早期诊断。
通过向12只雄性裸鼠的右膝关节腔内注射胶原酶(1.0%,w/v)诱导骨关节炎。左膝关节作为阴性对照。组织蛋白酶B NIR探针被与关节炎相关的组织蛋白酶B激活,从而产生强烈的近红外荧光信号,可在体内检测到。使用激发波长为610 - 650 nm和发射波长为680 - 720 nm的光学成像系统采集近红外荧光信号。
胶原酶注射1个月后观察到轻度至中度的软骨退变。小鼠的近红外荧光成像显示,在静脉注射报告探针24小时后,骨关节炎关节与正常关节之间的信号强度存在约3倍的差异。免疫组织化学评估还显示,组织蛋白酶B在股骨胫关节的关节炎病变中表达,而在对侧对照膝关节中不表达。
由于组织蛋白酶B可激活的近红外荧光成像显示骨关节炎关节与正常关节之间存在显著差异,因此组织蛋白酶B可激活的近红外荧光探针为骨关节炎的早期诊断提供了一种潜在的新成像技术。