STING-Targeted PET Imaging for Specific Detection and Therapeutic Monitoring of Myocarditis

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.