Imaging strategies for the specific detection and therapeutic monitoring of myocarditis are still lacking. Stimulator of interferon genes (STING) is a signal transduction molecule involved in an innate immune response. Here, we evaluated the feasibility of the recently developed STING-targeted radiotracer [¹⁸F]FBTA for positron emission tomography (PET) imaging to detect myocardial inflammation and monitor treatment in myocarditis mice. [¹⁸F]FBTA-PET imaging was performed in myocarditis mice and normal mice to verify the specificity of [¹⁸F]FBTA for the diagnosis of myocarditis. We also performed PET imaging in mice with myocarditis treated to verify the ability of [¹⁸F]FBTA in therapeutic monitoring. The expression of STING and inflammatory cell types was confirmed by flow cytometry and immunohistochemistry. [¹⁸F]FDG-PET imaging of myocarditis was used as a contrast. [¹⁸F]FBTA-PET imaging showed that the average radioactive uptake was significantly higher in the hearts of the myocarditis group than in the control group. STING was highly overexpressed in cardiac inflammatory cells, including macrophages, dendritic cells (DCs), and T cells. However, there was no significant difference in cardiac radiotracer uptake of [¹⁸F]FDG between the myocarditis group and the control group. Moreover, cardiac uptake of [¹⁸F]FBTA was significantly reduced in cyclosporin A-treated myocarditis mice and myocardial STING expression was also significantly reduced after the treatment. Overall, we showed that a STING-targeted PET tracer [¹⁸F]FBTA can be used to monitor changes in the inflammatory microenvironment in myocarditis. Besides, [¹⁸F]FBTA-PET is also suitable for real-time monitoring of myocarditis treatment, representing a promising diagnostic and therapeutic monitoring approach for myocarditis.

中文翻译：

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用于心肌炎特异性检测和治疗监测的 STING 靶向 PET 成像

心肌炎的特异性检测和治疗监测的影像学策略仍然缺乏。干扰素基因刺激物（STING）是一种参与先天免疫反应的信号转导分子。在这里，我们评估了最近开发的 STING 靶向放射性示踪剂 [ ¹⁸ F]FBTA 用于正电子发射断层扫描 (PET) 成像以检测心肌炎症并监测心肌炎小鼠治疗的可行性。对心肌炎小鼠和正常小鼠进行[ ^{18 F]FBTA-PET成像，验证[ 18} F]FBTA诊断心肌炎的特异性。我们还在接受治疗的心肌炎小鼠中进行了 PET 成像，以验证 [ ¹⁸ F]FBTA 在治疗监测中的能力。通过流式细胞术和免疫组织化学证实了 STING 和炎症细胞类型的表达。使用心肌炎的[ ¹⁸ F]FDG-PET成像作为对比。 [ ¹⁸ F]FBTA-PET显像显示，心肌炎组心脏平均放射性摄取量显着高于对照组。 STING 在心脏炎症细胞中高度过表达，包括巨噬细胞、树突状细胞 (DC) 和 T 细胞。然而，心肌炎组和对照组之间心脏放射性示踪剂[ ¹⁸ F]FDG的摄取没有显着差异。此外，环孢素A治疗的心肌炎小鼠心脏对[ ¹⁸ F]FBTA的摄取显着减少，治疗后心肌STING表达也显着减少。总体而言，我们表明，针对 STING 的 PET 示踪剂 [ ¹⁸ F]FBTA 可用于监测心肌炎炎症微环境的变化。此外，[ ¹⁸ F]FBTA-PET还适用于心肌炎治疗的实时监测，代表了一种有前途的心肌炎诊断和治疗监测方法。