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）与正电子发射断层扫描/计算机断层扫描 (PET/CT) 相结合，以非侵入性方式评估铁响应产品双氢青蒿素 (DHA) 在治疗中的潜力。治疗类风湿性关节炎。

 程序

从建立鸡II型胶原诱导关节炎（CIA）大鼠模型40天起，将20只具有一一对应关节炎指数（AI）评分的大鼠随机分为两组。一组口服DHA（剂量为1.5ml/（kg·天），每1ml含20mg DHA），持续15天；另一组接受脑卒中生理盐水溶液（SSS，1.5ml/（kg·天）），持续15天。第0天（D0）、第5天（D5）、第10天进行^68Ga柠檬酸盐微型PET/CT成像数据重建后，在口服给药第15天（D10）和第15天（D15），在横向CT上测量每只大鼠的踝关节横截面长度“ d ”，以及踝关节和肌肉的SUV _max 。显微PET/CT收集后测量背景进行统计分析，通过HE染色观察踝关节组织。

 结果

DHA组踝关节肿胀得到显着抑制，而SSS组则没有显着抑制。 ⁶⁸ Ga-柠檬酸盐显微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组和SSS组之间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AI评分和T/NT随时间逐渐升高，SSS组评分逐渐下降。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，铁反应产物 DHA 在关节炎中的抗炎作用可以通过类铁放射性示踪剂（ ⁶⁸ Ga-柠檬酸盐）进行监测。