Experimental study of 99Tcm-3PRGD2 imaging on the angiogenesis of rheumatoid arthritis

Objective To observe the uptake of 99Tcm-3 polyethylene glycol Arg-Gly-Asp dimer (3PRGD2) in rat models of rheumatoid arthritis (RA), in order to provide theoretical foundation for early diagnosis of RA. Methods The healthy female SD rats were divided into collagen induced arthritis (CIA) group (n=100), osteoarthritis (OA) group (n=20) and control group (n=20). Bovine collagen type Ⅱ emulsion was used for arthritis induction to establish CIA models. OA models were established by injection of L-cysteine and papain. Gamma imaging was performed before and 15 d, 30 d after the model establishment. The mediastinum was selected as non-target (NT) area and the target (T)/NT ratios were calculated. The serum levels of vascular endothelial growth factor (VEGF), tumor necrosis factor-α (TNF-α), αVβ3 before and after the model establishment were measured. Pathological and immunohistochemical detection were performed. One-way analysis of variance, Pearson and Spearman correlation analyses were used to analyze the data. Results There were 58 CIA models successfully established. Before the model establishment, T/NT ratios of CIA group, OA group and control group were 0.215±0.049, 0.210±0.050, 0.209±0.051, respectively (F=0.093, P>0.05). The T/NT ratios of the above three groups were 0.405±0.230, 0.223±0.045, 0.211±0.049 (F=12.601, P<0.05) 15 d post-model establishment, and those were 0.572±0.182, 0.238±0.045, 0.212±0.055 (F=65.147, P<0.05) 30 d post-model establishment. T/NT ratios of CIA group were positively correlated with the levels of serum VEGF, TNF-α, αVβ3, pathological score and the levels of immunohistochemical markers (VEGF, TNF-α, αVβ3, CD31, CD34; r values: 0.391-0.721, rs values: 0.365-0.669, all P<0.05). Conclusion 99Tcm-3PRGD2 can be specifically up-taken by RA lesions in rat models, thus has the potential in early synovial neovascularization imaging of RA. Key words: Arthritis, rheumatoid; Synovial membrane; Neovascularization, pathologic; Radionuclide imaging; Arg-Gly-Asp; Rats