Nuclear imaging of PD-L1 expression promotes the synergistic antitumor efficacy of targeted radionuclide therapy and immune checkpoint blockade

作者：Jiyun Shi, Hannan Gao, Yue Wu, Chuangwei Luo, Guangjie Yang, Qi Luo, Bing Jia, Chuanhui Han, Zhaofei Liu, Fan Wang · 发表于：European Journal of Nuclear Medicine and Molecular Imaging · 年份：2024 · DOI：10.1007/s00259-024-06962-w · 被引用次数：10 · 研究领域：Cancer Immunotherapy and Biomarkers、Radiopharmaceutical Chemistry and Applications、Neuroendocrine Tumor Research Advances

In order to maximize synergistic effect of targeted radionuclide therapy (TRT) and immune checkpoint blockade (ICB) as well as reduce the toxicity, we pioneered a strategy guided by PD-L1-targeted nuclear medicine imaging for the combination of TRT and ICB towards precision cancer therapy. As a novel targeted radiotherapeutic agent, 177 Lu-AB-3PRGD 2 targeting integrin α v β 3 was developed to achieve sustained antitumor effect by introducing an albumin binder (AB) into the structure of 3PRGD 2 . The 177 Lu-AB-3PRGD 2 TRT as well as different types of combination therapies of 177 Lu-AB-3PRGD 2 TRT and anti-PD-L1 ICB were performed in animal models. The changes of PD-L1 expression in tumors after TRT were evaluated in vitro and in vivo by PD-L1-specific SPECT/CT imaging of 99m Tc-MY1523. 177 Lu-AB-3PRGD 2 showed improved tumor uptake and prolonged tumor retention, leading to significantly enhanced tumor growth suppression. Moreover, 177 Lu-AB-3PRGD 2 TRT remodeled the tumor immune microenvironment by upregulating PD-L1 expression and increasing tumor-infiltrating CD8 + T cells, facilitating immunotherapy. We found that the anti-PD-L1 treatment was more effective during the upregulation of tumor PD-L1 expression, and the time window could be determined by 99m Tc-MY1523 SPECT/CT. We developed a novel and long-acting radiotherapeutic agent 177 Lu-AB-3PRGD 2 , and pioneered a strategy guided by PD-L1-targeted nuclear medicine imaging for the combination of TRT and ICB towards prec...