Novel STING-targeted PET radiotracer for alert and therapeutic evaluation of acute lung injury

新型 STING 靶向 PET 放射性示踪剂用于急性肺损伤的警报和治疗评估

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作者:Duo Xu, Fan Yang, Jiayao Chen, Tianxing Zhu, Fen Wang, Yitai Xiao, Zibin Liang, Lei Bi, Guolong Huang, Zebo Jiang, Hong Shan, Dan Li

Abstract

Acute lung injury (ALI), as a common clinical emergency, is pulmonary edema and diffuse lung infiltration caused by inflammation. The lack of non-invasive alert strategy, resulting in failure to carry out preventive treatment, means high mortality and poor prognosis. Stimulator of interferon genes (STING) is a key molecular biomarker of innate immunity in response to inflammation, but there is still a lack of STING-targeted strategy. In this study, a novel STING-targeted PET tracer, [18F]FBTA, was labeled with high radiochemical yield (79.7 ± 4.3%) and molar activity (32.5 ± 2.9 GBq/μmol). We confirmed that [18F]FBTA has a strong STING binding affinity (Kd = 26.86 ± 6.79 nmol/L) and can be used for PET imaging in ALI mice to alert early lung inflammation and to assess the efficacy of drug therapy. Our STING-targeted strategy also reveals that [18F]FBTA can trace ALI before reaching the computed tomography (CT) diagnostic criteria, and demonstrates its better specificity and distribution than [18F]fluorodeoxyglucose ([18F]FDG).

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