Development of 18F-Labeled Acridone Analogue for Tumor Imaging via Stimulator of Interferon Genes Targeting
- Mol Pharm. 2023 Jul 3;20(7):3529-3538. doi: 10.1021/acs.molpharmaceut.3c00137.
- 1. State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, China.
- 2. Department of Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China.
- 3. Institute of Clinical Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China.
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 Kd = 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.