99Tc^m-3PRGD2对类风湿关节炎新生血管靶向受体显像的实验研究

Experimental study of 99Tcm-3PRGD2 targeted receptor imaging on angiogenesis in rheumatoid arthritis

目的探讨99Tcm-联肼尼克酰胺-3聚乙二醇-精氨酸-甘氨酸-天冬氨酸环肽二聚体(3PRGD2)对类风湿关节炎(RA)早期诊断的可行性。方法取60只雌性Wistar大鼠,分为空白对照组10只(注射生理盐水0.3 ml/只)、胶原诱导性关节炎(CIA)组50只(注射Ⅱ型胶原乳剂0.3 ml/只)。2组均在造模前及造模后25和45 d行99Tcm-3PRGD2平面显像,测量并分析造模成功的CIA组大鼠在造模前后病变关节与纵隔的靶/非靶比值(T/NT)变化情况,并与同期空白对照组进行比较;另行病理学检测。采用重复测量方差分析和两独立样本t检验分析数据。结果CIA组32只大鼠造模成功,显像示病变关节有明显的滑膜炎及滑膜增厚特征,并有血管翳形成。32只CIA组大鼠造模前及造模后25和45 d病变关节部位T/NT分别为0.158±0.023、0.402±0.144和0.705±0.163(F=286.924,P<0.01)。造模后25和45 d时CIA组大鼠病变关节部位T/NT与空白对照组相应结果(0.160±0.028和0.158±0.032)比较差异均有统计学意义(t值:-10.484和-20.917,均P<0.01)。免疫组织化学检查示CIA组大鼠病变关节滑膜组织血管内皮生长因子、αvβ3、肿瘤坏死因子-α呈阳性表达。结论99Tcm-3PRGD2对大鼠RA模型关节滑膜新生血管显像的灵敏度高,有望用于RA的早期诊断。

Objective To investigate the feasibility of 99Tcm-hydrazinonicotinamide-(poly-(ethylene glycol))4-E[(poly-(ethylene glycol))4-c((Arg-Gly-Asp)fK)]2(3PRGD2)in the early diagnosis of rheumatoid arthritis(RA).Methods Sixty female Wistar rats were divided into control group(n=10;injected with saline of 0.3 ml/piece)and collagen-induced arthritis(CIA)group(n=50;injected with typeⅡcollagen emulsion of 0.3 ml/piece).Rats in 2 groups were subjected to 99Tcm-3PRGD2 planar imaging before modeling,25 and 45 d after modeling.The changes of the target/non-target ratio(T/NT)of the lesion joint and mediastinum before and after modeling were measured and analyzed in CIA rats,and compared with rats in control group.Pathological examination was conducted.Repeated measures analysis of variance and independent-sample t test were used to analyze the data.Results Thirty-two rats in CIA group were successfully established,and obvious synovitis and synovial thickening,neovascularization were observed in the images.The T/NT of diseased joints in CIA group before modeling,25 and 45 d after modeling were 0.158±0.023,0.402±0.144,and 0.705±0.163(F=286.924,P<0.01).The T/NT of diseased joints at 25 and 45 d after modeling were significantly different from those of control group(0.160±0.028 and 0.158±0.032;t values:-10.484 and-20.917,both P<0.01).Immunohistochemistry results showed positive expressions of vascular endothelial growth factor,αvβ3 and tumor necrosis factor-αin the synovial tissue in of diseased joints in rats of CIA group.Conclusion 99Tcm-3PRGD2 has high sensitivity for joint synovial neovascularization in rat rheumatoid arthritis models and is expected to be used for early diagnosis of RA.