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.