Small-Molecule Radiotracers for Visualization of V-Domain Immunoglobulin Suppressor of T Cell Activation

  • J Med Chem. 2024 Oct 10;67(19):17690-17700. doi: 10.1021/acs.jmedchem.4c01690.
Jia Liu  1  2 ,  Yuanyuan Liang  1 ,  Hongzhang Yang  1 ,  Xueqi Wang  1 ,  Xinying Zeng  1 ,  Rongqiang Zhuang  1 ,  Jin Du  2  3  4 ,  Xianzhong Zhang  5 ,  Zhide Guo  1
Affiliations
  • 1. 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 Road, Xiamen 361102, China.
  • 2. Department of Nuclear Technology and Application, China Institute of Atomic Energy, P.O. Box 275(12), Beijing 102413, China.
  • 3. China Isotope & Radiation Corporation, No. 66 Changwa Zhongjie, Haidian, Beijing 100089, China.
  • 4. CAEA Center of Excellence on Nuclear Technology Application for Engineering and Industrialization of Radiopharmaceuticals, No. 1 Sanqiang Road, Xinzhen, Fangshan District, Beijing 102413, China.
  • 5. 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, Beijing 100730, China.
PMID: 39305257 DOI: 10.1021/acs.jmedchem.4c01690
Abstract

V-domain immunoglobulin suppressor of T cell activation (VISTA) plays a critical role in regulating innate and adaptive immune responses within the tumor immune microenvironment. Quantifying VISTA expression is necessary to determine whether patients respond to a related combination immunotherapy. This study developed two 68Ga-labeled small-molecule probes ([68Ga]Ga-DCA and [68Ga]Ga-DNCA) for visualizing and differentiating VISTA expression. These probes exhibited excellent targeting capabilities for multiple tumor types (including B16-F10, 4T1, MC38, and CT26 tumors), consistent with the levels of VISTA expression determined by immunoblotting. Co-injection of inhibitor CA-170 led to decreased tumor uptake of both [68Ga]Ga-DCA and [68Ga]Ga-DNCA. [68Ga]Ga-DCA was used to verify the feasibility of monitoring VISTA expression in lung metastasis models. In summary, this study describes the use of 68Ga-labeled CA-170 analogues as small-molecule probes for imaging VISTA. This could provide a visual method and enable personalized immunotherapy in patients.

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