Early detection of rheumatoid arthritis in rats and humans with 99mTc-3PRGD2 scintigraphy: imaging synovial neoangiogenesis.
Early detection of rheumatoid arthritis in rats and humans with 99mTc-3PRGD2 scintigraphy: imaging synovial neoangiogenesis.
复制标题
使用 99mTc-3PRGD2 闪烁扫描术早期检测大鼠和人类的类风湿性关节炎：滑膜新生血管生成成像
DOI：
10.18632/oncotarget.13953
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发表时间：
2017-01-24
期刊：
影响因子：
--
通讯作者：
Li XF
中科院分区：
文献类型：
--
作者：
Wu Y;Zhang G;Wang X;Zhao Z;Wang T;Wang X;Li XF
目的：验证99 mTc-3 PRGD 2骨显像作为类风湿性关节炎关节滑膜新生血管成像的方法，并研究其在类风湿性关节炎早期检测和治疗中的潜力。研究方法：分别通过II型胶原免疫和木瓜蛋白酶注射在Sprague道利大鼠中产生类风湿性关节炎和骨关节炎。用99 mTc-3 PRGD 2和99 mTc-甲基二膦酸盐（99 mTc MDP）对大鼠成像。还获得了X线图像，并由放射科医生进行了评估。αvβ3和CD 31的免疫组化证实了滑膜新生血管的发生。用99 mTc-3 PRGD 2放射性核素显像观察贝伐单抗对类风湿关节炎的疗效。用99 mTc-3 PRGD 2对1例类风湿关节炎患者和1例健康志愿者进行了全身显像。结果如下：免疫后两周，在类风湿性关节炎模型的关节中观察到99 mTc-3 PRGD 2的显著增加，尽管骨关节炎模型和未处理对照中的摄取较低。99 mTc-MDP全身扫描未能区分早期类风湿性关节炎关节和健康对照。αvβ3和CD 31在类风湿关节炎大鼠关节中的表达明显高于正常对照组。在系列99 mTc-3 PRGD 2放射成像研究中，99 mTc-3 PRGD 2摄取与疾病进展平行增加。贝伐单抗抗血管生成治疗既改善了类风湿性关节炎大鼠的症状，又显著降低了99 mTc-3 PRGD 2的摄取。在患者的类风湿性关节炎关节中也观察到显著更高的99 mTc-3 PRGD 2积累。结论：我们的研究结果表明，99 mTc-3 PRGD 2骨显像可以检测早期类风湿性关节炎通过成像相关的滑膜新生血管，并可能是有用的疾病管理。
Objectives: To validate 99mTc-labeled arginylglycylaspartic acid (99mTc-3PRGD2) scintigraphy as a means to image synovial neoangiogenesis in joints afflicted by rheumatoid arthritis and to investigate its potential in the early detection and management of rheumatoid arthritis. Methods: Rheumatoid arthritis and osteoarthritis were generated in Sprague Dawley rats by type II collagen immunization and papain injection, respectively. Rats were imaged with 99mTc-3PRGD2 and 99mTc- methyl diphosphonate (99mTc MDP). X-ray images were also obtained and assessed by a radiologist. Immunohistochemistry of αvβ3 and CD31confirmed the onset of synovial neoangiogenesis. The effect of bevacizumab on rheumatoid arthritis was followed with 99mTc-3PRGD2 scintigraphy. A patient with rheumatoid arthritis and a healthy volunteer were scanned with 99mTc-3PRGD2. Results: Two weeks after immunization, a significant increase in 99mTc-3PRGD2 was observed in the joints of the rheumatoid arthritis model though uptake in osteoarthritis model and untreated controls was low. 99mTc-MDP whole body scans failed to distinguish early rheumatoid arthritis joints from healthy controls. The expression of αvβ3 and CD31was significantly higher in the joints of rheumatoid arthritis rats compared to normal controls. In serial 99mTc-3PRGD2 scintigraphy studies, 99mTc-3PRGD2 uptake increased in parallel with disease progression. Bevacizumab anti-angiogenetic therapy both improved the symptoms of the rheumatoid arthritis rats and significantly decreased 99mTc-3PRGD2 uptake. Significantly higher 99mTc-3PRGD2 accumulation was also observed in rheumatoid arthritis joints in the patient. Conclusions: Our findings indicate that 99mTc-3PRGD2 scintigraphy could detect early rheumatoid arthritis by imaging the associated synovial neoangiogenesis, and may be useful in disease management.