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.

T细胞活化免疫球蛋白V结构域抑制因子（VISTA）在肿瘤免疫微环境中对固有免疫与适应性免疫应答具有关键调控作用。定量检测VISTA的表达水平，是判断患者是否对相关联合免疫疗法产生应答的必要前提。本研究开发了两种68Ga标记的小分子探针（[68Ga]Ga-DCA与[68Ga]Ga-DNCA），用于可视化成像并区分VISTA的表达水平。上述探针对多种肿瘤模型（包括B16-F10、4T1、MC38及CT26肿瘤）展现出优异的靶向能力，且这一结果与免疫印迹法检测得到的VISTA表达水平相符。共注射抑制剂CA-170后，两种探针[68Ga]Ga-DCA与[68Ga]Ga-DNCA的肿瘤摄取量均出现下降。本研究使用[68Ga]Ga-DCA验证了在肺转移模型中监测VISTA表达的可行性。综上，本研究报道了以68Ga标记的CA-170类似物作为小分子探针用于VISTA成像的研究思路，该方法可为患者提供可视化检测手段，助力实现个性化免疫治疗。