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

Abstract

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 type Ⅱ collagen 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-α in 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. Key words: Arthritis, rheumatoid; Neovascularization, pathologic; Radionuclide imaging; Arginine-glycine-aspartic acid; Rats