Development of 18F-Labeled Acridone Analogue for Tumor Imaging via Stimulator of Interferon Genes Targeting

The stimulator of interferon genes (STING) is a pivotal protein in the production of STING-dependent type I interferon, which has the potential to enhance tumor rejection. The visualization of STING in the tumor microenvironment is valuable for STING-related treatments, but few STING imaging probes have been reported to date. In this study, we developed a novel ¹⁸F-labeled agent ([¹⁸F]F-CRI1) with an acridone core structure for the positron emission tomography (PET) imaging of STING in CT26 tumors. The probe was successfully prepared with a nanomolar STING binding affinity of K_d = 40.62 nM. [¹⁸F]F-CRI1 accumulated quickly in the tumor sites and its uptake reached a maximum of 3.02 ± 0.42% ID/g after 1 h i.v. injection. The specificity of [¹⁸F]F-CRI1 was confirmed both in in vitro cell uptake and in vivo PET imaging by blocking studies. Our findings suggest that [¹⁸F]F-CRI1 may be a potential agent for visualizing STING in the tumor microenvironment.

18F-labeling; PET imaging; STING targeting; acridone derivative; tumor microenvironment.