Purpose: Stimulator of interferon genes (STING) protein plays a vital role in the immune surveillance of tumor microenvironment. Monitoring STING expression in tumors benefits the relevant STING therapy. This study aimed to develop a novel F-labeled agonist, dimeric amidobenzimidazole (diABZI), and firstly evaluate the feasibility of noninvasive positron emission tomography (PET) imaging of STING expression in the tumor microenvironment.
Methods: An analog of the STING agonist NOTA-DABI was synthesized and labeled with F via AlF-NOTA complexation (denoted as [F]F-DABI). Physicochemical properties, STING protein-binding affinity, and specificity of [F]F-DABI were evaluated using cell uptake and docking assays. In vivo small-animal PET imaging and biodistribution studies of [F]F-DABI in tumor-bearing mice were performed to verify the pharmacokinetics and tumor targeting ability. The correlation between tumor uptake and STING expression was also analyzed.
Results: [F]F-DABI was produced conveniently with high radiochemical yield (44 ± 15%), radiochemical purity (> 97%) and molar activity (15-30 GBq/μmol). In vitro binding assays demonstrated that [F]F-DABI has a favorable affinity and specificity for STING with a K of 12.98 ± 2.07 nM. In vivo studies demonstrated the specificity of [F]F-DABI for PET imaging of STING expression with B16F10 tumor uptake of 10.93 ± 0.93%ID/g, which was significantly different from that of blocking groups (3.13 ± 0.88%ID/g, p < 0.0001). Furthermore, tumor uptake of [F]F-DABI was well positively correlated with STING expression in different tumor types. Biodistribution results demonstrated that [F]F-DABI was predominately uptaken in the liver and intestines, indicating its hepatobiliary elimination.
Conclusion: This proof-of-concept study demonstrated a STING-binding radioligand for PET imaging, which could be used as a potential companion diagnostic tool for related STING-agonist therapies.
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