Purpose

We aimed to use ⁶⁸Ga-citrate, a labeled product of gallium (iron analog), combined with positron emission tomography/computed tomography (PET/CT) to non-invasively evaluate the potential of the iron-responsive product dihydroartemisinin (DHA) in the treatment of rheumatoid arthritis.

Procedures

From the establishment of chicken II collagen-induced arthritis (CIA) rat model over 40 days, 20 rats with one-to-one corresponding arthritis index (AI) scores were randomly divided into two groups. One group received oral DHA (at a dose of 1.5 ml/(kg day), containing 20 mg DHA per 1 ml) for 15 days; the other group received stroke-physiological saline solution (SSS, 1.5 ml/(kg day) for 15 days. ⁶⁸Ga-citrate micro-PET/CT imaging was performed on day 0 (D0), day 5 (D5), day 10 (D10), and day 15 (D15) of oral administration. After data reconstruction, the cross-sectional length “d” of the ankle joint of each rat was measured on the transverse CT, and the SUV_max of the ankle joint and muscle background was measured for statistical analysis. After micro-PET/CT collection, the ankle joint tissue was observed by HE staining.

Results

The ankle joint swelling in the DHA group was significantly suppressed, but the SSS group showed no significant suppression. ⁶⁸Ga-citrate micro-PET/CT imaging results and microscope observation confirmed this finding. Statistical analysis indicated that the time tendency of AI score (B_interaction = 0.495, P < 0.001) and T/NT (B_interaction = 1.345, P < 0.001) were discrepant between DHA and SSS groups. The AI score and T/NT of the DHA group gradually increased with time, while the SSS group score gradually decreased. Furthermore, the Spearman correlation coefficient was used to describe the relationship between “d” and T/NT, which was positively correlated (r = 0.855, P < 0.001).

Conclusions

This study showed that the anti-inflammatory effect of the iron-responsive product DHA in arthritis can be monitored by an iron-like radioactive tracer (⁶⁸Ga-citrate).

中文翻译：

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68Ga-柠檬酸盐 PET/CT 成像对双氢青蒿素治疗类风湿性关节炎的评价。

目的

我们的目标是使用⁶⁸ Ga-柠檬酸盐，一种镓（铁类似物）的标记产品，结合正电子发射断层扫描/计算机断层扫描 (PET/CT)，以非侵入性的方式评估铁反应性产品双氢青蒿素 (DHA) 在治疗中的潜力。类风湿性关节炎的治疗。

程序

从建立鸡II型胶原性关节炎（CIA）大鼠模型40天后，将20只具有一比一对应关节炎指数（AI）评分的大鼠随机分为两组。一组接受口服DHA（剂量为1.5毫升/（公斤天），每1毫升含20毫克DHA）15天；另一组接受中风生理盐水（SSS，1.5 ml/（kg day），持续15天。在第0天（D0）、第5天（D5）、第10天进行⁶⁸ Ga-citrate micro-PET/CT成像(D10)、口服给药第15天(D15)。数据重建后，在横断面CT上测量每只大鼠踝关节的横截面长度“ d ”，SUV _max对踝关节和肌肉背景进行测量以进行统计分析。micro-PET/CT采集后，HE染色观察踝关节组织。

结果

DHA组踝关节肿胀明显受到抑制，但SSS组无明显抑制。⁶⁸ Ga-citrate micro-PET/CT 成像结果和显微镜观察证实了这一发现。统计分析表明， DHA和SSS组的AI评分（B_交互作用 =0.495，P  <0.001）和T/NT（B_交互作用 =1.345，P <0.001）的时间趋势存在差异。DHA组的AI评分和T/NT随时间逐渐升高，而SSS组评分逐渐降低。此外，用Spearman相关系数来描述“ d ”与T/NT之间的关系，呈正相关（r  = 0.855，P  < 0.001）。

结论

这项研究表明，铁反应性产品 DHA 在关节炎中的抗炎作用可以通过铁样放射性示踪剂 ( ⁶⁸ Ga-柠檬酸盐)进行监测。