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Development of STING probes and visualization of STING in multiple tumor types.
Liu, Huanhuan; Liu, Jia; Chen, Yingxi; Yang, Hongzhang; Fang, Jianyang; Zeng, Xinying; Zhang, Jingru; Peng, Shilan; Liang, Yuanyuan; Zhuang, Rongqiang; Liu, Gang; Zhang, Xianzhong; Guo, Zhide.
Afiliación
  • Liu H; State Key Laboratory of Vaccines for Infectious Diseases, Center for Molecular Imaging and Translational Medicine, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, 4221-116 Xiang'An South Rd, Xiamen, 361102, China.
  • Liu J; State Key Laboratory of Vaccines for Infectious Diseases, Center for Molecular Imaging and Translational Medicine, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, 4221-116 Xiang'An South Rd, Xiamen, 361102, China.
  • Chen Y; Department of Nuclear Technology and Application, China Institute of Atomic Energy, P.O. Box 275(12), Beijing, 102413, China.
  • Yang H; State Key Laboratory of Vaccines for Infectious Diseases, Center for Molecular Imaging and Translational Medicine, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, 4221-116 Xiang'An South Rd, Xiamen, 361102, China.
  • Fang J; State Key Laboratory of Vaccines for Infectious Diseases, Center for Molecular Imaging and Translational Medicine, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, 4221-116 Xiang'An South Rd, Xiamen, 361102, China.
  • Zeng X; State Key Laboratory of Vaccines for Infectious Diseases, Center for Molecular Imaging and Translational Medicine, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, 4221-116 Xiang'An South Rd, Xiamen, 361102, China.
  • Zhang J; State Key Laboratory of Vaccines for Infectious Diseases, Center for Molecular Imaging and Translational Medicine, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, 4221-116 Xiang'An South Rd, Xiamen, 361102, China.
  • Peng S; State Key Laboratory of Vaccines for Infectious Diseases, Center for Molecular Imaging and Translational Medicine, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, 4221-116 Xiang'An South Rd, Xiamen, 361102, China.
  • Liang Y; State Key Laboratory of Vaccines for Infectious Diseases, Center for Molecular Imaging and Translational Medicine, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, 4221-116 Xiang'An South Rd, Xiamen, 361102, China.
  • Zhuang R; State Key Laboratory of Vaccines for Infectious Diseases, Center for Molecular Imaging and Translational Medicine, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, 4221-116 Xiang'An South Rd, Xiamen, 361102, China.
  • Liu G; State Key Laboratory of Vaccines for Infectious Diseases, Center for Molecular Imaging and Translational Medicine, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, 4221-116 Xiang'An South Rd, Xiamen, 361102, China. zhrq@xmu.edu.cn.
  • Zhang X; State Key Laboratory of Vaccines for Infectious Diseases, Center for Molecular Imaging and Translational Medicine, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, 4221-116 Xiang'An South Rd, Xiamen, 361102, China. gangliu.cmitm@xmu.edu.cn.
  • Guo Z; Theranostics and Translational Research Center, Institute of Clinical Medicine, Department of Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 1 Shuaifuyuan, Dongcheng District, Beijing, 100730, China. zhangxzh@pumch
Article en En | MEDLINE | ID: mdl-39289182
ABSTRACT

PURPOSE:

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.

METHODS:

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-CRIn 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.

RESULTS:

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.

CONCLUSION:

In summary, this work demonstrated a promising pathway for the development of STING-targeted radioprobes, advancing in vivo PET imaging capabilities.
Palabras clave

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Eur J Nucl Med Mol Imaging Asunto de la revista: MEDICINA NUCLEAR Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Alemania

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Eur J Nucl Med Mol Imaging Asunto de la revista: MEDICINA NUCLEAR Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Alemania