Development of STING probes and visualization of STING in multiple tumor types.

Abstract

The stimulator of interferon genes (STING) is a critical component of the innate immune system and plays a pivotal role in tumor immunotherapy. Developing non-invasive in vivo diagnostic methods for visualizing STING is highly valuable for STING-related immunotherapy. This work aimed to build a noninvasive imaging platform that can dynamically and quantitatively monitor tumor STING expression. We investigated the in vivo positron emission tomography (PET) imaging of STING-expressing tumors (B16F10, MC38, and Panc02) with STING-targeted radioprobe ([¹⁸F]F-CRI₁). The expression of STING in tumors was quantified, and correlation analysis was performed between these results and the outcomes of PET imaging. Furthermore, we optimized the structure of [¹⁸F]F-CRI_n with polyethylene glycol (PEG) to improve the pharmacokinetic characteristics in vivo. A comprehensive comparison of the imaging and biodistribution results obtained with the optimized probes was conducted in the B16F10 tumors. The PET imaging results showed that the uptake of [¹⁸F]F-CRI₁ in tumors was positively correlated with the expression of STING in tumors (r = 0.9184, P < 0.001 at 0.5 h). The lipophilicity of the optimized probes was significantly reduced. As a result of employing optimized probes, B16F10 tumor-bearing mice exhibited significantly improved tumor visualization in PET imaging, along with a marked reduction in retention within non-target areas such as the gallbladder and intestines. Biodistribution experiments further validated the efficacy of probe optimization in reducing uptake in non-target areas. In summary, this work demonstrated a promising pathway for the development of STING-targeted radioprobes, advancing in vivo PET imaging capabilities.