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类风湿性关节炎(rheumatoid arthritis,RA)是一种病因不明,以慢性、对称性、侵蚀性关节炎为主要表现的全身性自身免疫疾病。患者可出现严重的关节畸形及功能丧失,致残率及病死率较高。该病不仅严重影响患者的生活质量,还给社会带来了巨大的经济负担,目前临床上尚无有效措施逆转已经发生的关节破坏。而关节破坏在病程的早期(1年,甚至4个月内)就可出现,如能早期诊断RA,积极治疗后可控制和延缓病情发展,显著降低致残率[1]。因此,RA的早期诊断成为改善RA预后的关键,近年来已成为国内外学者的研究热点。
研究发现RA的早期诊断主要在于对RA的滑膜血管翳的检测。因为滑膜血管翳形成是RA最基本、最重要的病理表现,也是RA区别于其他关节炎的重要特征。血管翳形成导致软骨和骨破坏及关节重塑,最终导致关节畸形、功能丧失。而血管形成则是产生和维持RA血管翳的重要标志,它增强了血管翳的侵袭性,并同时促进血管翳形成,导致软骨和骨破坏,在RA的侵蚀和破坏过程中发挥了重要的作用,且血管形成在RA病程的早期便开始作用并贯穿整个病程[2]。因此,观察新生血管形成对于RA的早期诊断、活动性判断、疗效观察和预后判断均有重要意义[3]。但到目前为止仍没有较好的早期诊断RA的方法。
近年来随着分子影像学技术的发展,利用整合素αvβ3在肿瘤新生血管内皮细胞中高表达的特性,用99Tcm标记精氨酸-甘氨酸-天冬氨酸(Arginine-Glycine-Aspartic,RGD)的多肽,能特异地与细胞整合素αvβ3配体结合并通过SPECT在体检测新生血管,目前多项研究证实该方法是一种灵敏度高和特异性好的方法[4-5]。由此推测99Tcm-3PRGD2(其中,P为聚乙二醇)SPECT可能在体显示RA的新生血管(滑膜血管翳)。如果这种方法可行,将为RA早期诊断和筛选靶向治疗药物开辟新的方法。
99Tcm-RGD显像在类风湿性关节炎血管形成早期诊断的初步探讨
Applications of 99Tcm-RGD for angiogenesis in early diagnosis of rheumatoid arthritis
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摘要: 滑膜血管翳形成是类风湿性关节炎(RA)最基本、最重要的病理表现,可导致软骨和骨破坏及关节重塑,最终导致关节畸形、功能丧失。其中,血管形成在血管翳的侵蚀和破坏过程中发挥了重要的作用,增强了血管翳的侵袭性,促进了软骨和骨破坏。血管形成从RA病程的早期便开始作用并贯穿整个病程。因而观察血管形成对于RA的早期诊断、活动期判断、疗效观察和预后判断均有重要意义。99Tcm标记精氨酸-甘氨酸-天冬氨酸(RGD)的多肽是一种能与整合素αvβ3受体有高度的选择性和亲和力,并能在体反映血管形成情况的显像剂。因而可以利用99Tcm-RGD SPECT观察RA的滑膜血管翳形成和发展过程及血管形成拮抗剂抑制RA血管形成的规律,从而为RA的生物治疗提供更多的理论依据并寻找到更多的新靶向治疗药物。Abstract: Synovial pannus formation is the most basic and important pathological manifestation for rheumatoid arthritis(RA). This manifestation can lead to the destruction of cartilage, bone, and joint, ultimately leading to joint deformity and loss of function. Angiogenesis plays an important role in the process of synovial pannus formation, as well as the erosion and destruction of the pannus. Angiogenesis enhances the invasiveness of the pannus and promotes destruction of bone and cartilage. Angiogenesis began early in and throughout the course of the disease. Thus, angiogenesis should be observed for early diagnosis of RA, judgment of active stage, and assessment of therapy and prognosis. To examine the change rule of RA angiogenesis, the development course and antagonists of angiogenesis should inhibit this process to determine a further theoretical basis and novel drugs for targeted therapy with 99Tcm labeled arginine-glycine-aspartic acid(Arg-Gly-Asp, RGD) peptides. These peptides demonstrate high selectivity and affinity with the integrin αvβ3 receptor and can show angiogenesis-imaging agents via SPECT imaging in the body.
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Key words:
- Arthritis, rheumatoid /
- Angiogenesis /
- RGD imagin
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