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

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.