99mTc-3PRGD2靶向受体显像对类风湿性关节炎滑膜新生血管形成的实验研究

Synovial pannus formation is the most basic and important pathological manifestations for rheumatoid arthritis ( RA ).It can lead to the destruction of cartilage and bone and joint remodeling,and ultimately leading to joint deformity and loss of function. Angiogenesis played an important role in the process for Synovial pannus formation and its erosion and destruction.It enhance the pannus invasive and promote the destruction of bone and cartilage.Angiogenesis began to the course of early and throughout the course of the disease. .It is necessary to observed imaging of angiogenesis in vivo for early diagnosis of RA，judgment of active stage and observation of therapy and prognosis ..High target / non-target tissue uptake ratio in vivo SPECT imaging by 99mTc labled Arginine-Glycine-Aspartic acid (Arg-Gly-Asp, RGD) peptides which have high selectivity and affinity with the integrin αvβ3 receptors of neovascularization cell membrane of RA can observe RA angiogenesis . The molecular targeting receptor imaging study will offer experimental evidence for RA early diagnosis and screening of anti -angiogenesis biological targeted drug.

滑膜血管翳形成是类风湿性关节炎(rheumatoid arthritis ,RA)最重要的病理表现，可导致关节软骨和骨破坏及关节重塑，最终导致关节畸形、功能丧失。其中新生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。新生血管形成从RA病程的早期便开始作用并贯穿整个病程。在体显像研究血管形成对于RA的早期诊断、活动期判断、靶向治疗和预后判断均有重要意义。利用99mTc标记精氨酸-甘氨酸-天冬氨酸（Arg-Gly-Asp，RGD）的多肽，这个能与RA新生血管细胞表面高表达的整合素αvβ3受体高选择性和特异性结合的显像剂，通过在体SPECT显像的高的靶组织/非靶组织摄取比值来评价RA的滑膜新生血管形成，为RA的早期诊断和筛选抗新生血管形成生物靶向药物提供实验依据。

滑膜血管翳形成是类风湿性关节炎(rheumatoid arthritis ,RA)最重要的病理表现，可导致关节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。在体显像研究血管形成对于RA的早期诊断、活动期判断、靶向治疗和预后判断均有重要意义。利用99mTc标记精氨酸-甘氨酸-天冬氨酸（Arg-Gly-Asp，RGD）的多肽，这个能与RA新生血管细胞表面高表达的整合素αvβ3受体高选择性和特异性结合的显像剂，通过在体SPECT显像的高的靶组织/非靶组织摄取比值来反映RA血管形成情况，从而评价RA的滑膜血管翳形成及应用血管形成拮抗剂抑制RA血管形成治疗的效果。研究发现CAI组大鼠在注射造模成功后病变关节部位T/NT值与关节炎指数积分、血清VEGF 、TNF-α、αVβ3水平、病理评分损伤指数及滑膜组织中VEGF、TNF-α、αVβ3、CD31、CD34表达水平均呈正相关（r=0.562、0.721、0.521、0.391、0.606、0.408、0.561、0.594、0.669、0.365，P＜0.05）。经rhTNFR：Fc和贝伐单抗治疗后T／NT值均下降，T／NT值与关节炎指数积分、血清VEGF 、TNF-α、αVβ3水平、病理评分损伤指数及滑膜组织中VEGF、TNF-α、αVβ3、CD31、CD34表达水平均呈正相关(rhTNFR：Fc治疗组r=0.485，0.624,0.607,0.598，0.609，0.549，0.479,0.496,0.706，P＜0.05；贝伐单抗治疗组r=0.662，0.659,0.789,0.807，0.483，0.570，0.553,0.483,0.577，P＜0.05)。上述研究结果均证明99mTc-3PRGD2靶向受体显像剂对RA早期滑膜新生血管形成显像以及在筛选新的抗滑膜血管翳形成的靶向药物具有临床应用价值。