Small-Molecule\nRadiotracers for Visualization of V‑Domain\nImmunoglobulin Suppressor of T Cell Activation

V-domain\nimmunoglobulin suppressor of T cell activation\n(VISTA)\nplays a critical role in regulating innate and adaptive immune responses\nwithin the tumor immune microenvironment. Quantifying VISTA expression\nis necessary to determine whether patients respond to a related combination\nimmunotherapy. This study developed two <sup>68</sup>Ga-labeled small-molecule\nprobes ([<sup>68</sup>Ga]Ga-DCA and [<sup>68</sup>Ga]Ga-DNCA) for\nvisualizing and differentiating VISTA expression. These probes exhibited\nexcellent targeting capabilities for multiple tumor types (including\nB16-F10, 4T1, MC38, and CT26 tumors), consistent with the levels of\nVISTA expression determined by immunoblotting. Co-injection of inhibitor\nCA-170 led to decreased tumor uptake of both [<sup>68</sup>Ga]Ga-DCA\nand [<sup>68</sup>Ga]Ga-DNCA. [<sup>68</sup>Ga]Ga-DCA was used to\nverify the feasibility of monitoring VISTA expression in lung metastasis\nmodels. In summary, this study describes the use of <sup>68</sup>Ga-labeled\nCA-170 analogues as small-molecule probes for imaging VISTA. This\ncould provide a visual method and enable personalized immunotherapy\nin patients.