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Objective:To explore the therapeutic mechanism of Mongolian medicine Sendeng-4 decoction for rheumatoid arthritis by 99Tc m-hydrazinonicotinamide-(polyethylene glycol) 4-E[(polyethylene glycol) 4-c((Arg-Gly-Asp)fk)] 2 (3PRGD 2) imaging. Methods:A total of 200 female SD rats (age: 6-7 weeks) were divided into collagen-induced arthritis (CIA) group ( n=176) and blank control group ( n=24). Rats in the CIA group were divided into Sendeng-4 decoction treatment group ( n=24), etanercept treatment group ( n=24), and negative control group ( n=24) by simple random sampling method. 99Tc m-3PRGD 2 SPECT/CT imaging was performed before and after modeling and treatment. The differences of target/non-target (T/NT) ratio and serological, pathological, and immunohistochemical results among groups were compared by one-way analysis of variance or Kruskal-Wallis rank sum test. The correlation was analyzed by Pearson correlation or Spearman correlation analysis. Results:There were 95 (95/176) CIA models successfully established. The T/NT ratios of Sendeng-4 decoction treatment group and etanercept treatment group were lower than that of negative control group (0.260± 0.094, 0.238±0.099, 0.766±0.144 ; F=163.00, P<0.001), while there was no significant difference between the two drug treatment groups ( P>0.05). After drug treatment, serum levels of vascular endothelial growth factor (VEGF), tumor necrosis factor-α (TNF-α) and α vβ 3 were significantly lower than those of negative control group ( F values: 49.43-92.36, all P<0.001), pathological score was also lower than that of negative control group ( H=34.25, P<0.001), and levels of immunohistochemical makers (VEGF, TNF-α, α vβ 3, CD31, CD34) were also lower than those of negative control group ( H values: 13.51-26.84, all P<0.001), while there were no significant differences between the two drug treatment groups (all P>0.05). The T/NT ratios were positively correlated with above indictors in Sendeng-4 decoction treatment group ( r values: 0.56-0.59, rs values: 0.49-0.69), etanercept treatment group ( r values: 0.50-0.55, rs values: 0.46-0.70) and negative control group ( r values: 0.55-0.80, rs values: 0.58-0.86, P<0.001 or P<0.05). Conclusion:Verified by 99Tc m-3PRGD 2 SPECT/CT imaging and molecular pathology, Mongolian medicine Sendeng-4 decoction can inhibit neovascularization by down-regulating vascular factors such as VEGF, resulting in delaying the progression of the disease and improving clinical symptoms.
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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.
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Objective To synthesize 11 C-methyldopamine (MDA) and to explore its feasibility as an agent for cardiac sympathetic nerve imaging.Methods 11 C-MDA was synthesized by direct N-methylation method and purified by semi-preparation reverse HPLC.Thirty Kunming mice were divided into five groups by random number table.The mice were respectively sacrificed at 2,5,10,20 and 30 min after injection of 7.4 MBq 11C-MDA.The lung,liver,spleen,kidney,stomach,intestine,brain,muscle,bone tissues and blood of mice were removed and weighed before radioactive γ-counting.The ％ID/g was calculated.Six Chinese mini-swine were divided into normal group (n=3) and inhibition group (n =3) for myocardial imaging.Mini-swine of inhibition group were injected with 10 mg/kg imipramine hydrochloride at 30 min before 11C-MDA (370 MBq) injection.The data were analyzed with SPSS 15.0 software.Results The synthesis of 11 C-MDA took 45 min with radiochemical yields of (20±3)％.The solution of11 C-MDA was colorless and the pH value was 6.5.The radiochemical purity was more than 98％ and the specific activity was 50 GBq/mmol.The myocardial uptake reached the peak value of (8.78± 1.18) ％ID/g at 2 min after injection of 11 C-MDA in mice.11C-MDA was mainly metabolized through liver and kidney.PET/CT imaging showed that 11 C-MDA was highly uptaken in swine myocardium and could be blocked by imipramine hydrochloride.Conclusions 11C-MDA can be synthesized by a simple and economic method.The high uptake rate of 11 C-MDA in the heart suggests it may be a potential agent for cardiac nerve imaging.