A novel 18F-labeled agonist for PET imaging of stimulator of interferon gene expression in tumor-bearing mice.

Abstract

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 18F-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 18F via Al18F-NOTA complexation (denoted as [18F]F-DABI). Physicochemical properties, STING protein-binding affinity, and specificity of [18F]F-DABI were evaluated using cell uptake and docking assays. In vivo small-animal PET imaging and biodistribution studies of [18F]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:

[18F]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 [18F]F-DABI has a favorable affinity and specificity for STING with a KD of 12.98 ± 2.07 nM. In vivo studies demonstrated the specificity of [18F]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 [18F]F-DABI was well positively correlated with STING expression in different tumor types. Biodistribution results demonstrated that [18F]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.

• Authors: Jianyang Fang, Lixia Feng, Lingxin Meng, Xiaobo Wang, Huanhuan Liu, Lumei Huang, Deliang Zhang, Jingchao Li, Rongqiang Zhuang, Zhide Guo, Xianzhong Zhang
• Journal: European journal of nuclear medicine and molecular imaging (Eur J Nucl Med Mol Imaging) Vol. 50 Issue 1 Pg. 27-37 (Dec 2022) ISSN: 1619-7089 [Electronic] Germany
• PMID: 36066666 (Publication Type: Journal Article)
• Copyright: © 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Chemical References

• Fluorine Radioisotopes
• DABI
• Interferons

Topics

• Animals
• Mice
• Fluorine Radioisotopes (pharmacokinetics)
• Tissue Distribution
• Cell Line, Tumor
• Positron-Emission Tomography (methods)
• Gene Expression
• Interferons