Peptide-based PET/CT imaging visualizes PD-L1-driven radioresistance in glioblastoma

作者：Yong Wang, Zhiguo Liu, Yang Li, Kelin Wang, Chunhui Yuan, Jianxin Shi, Jiazhong Ren, Shijie Wang, Jinping Wang, Miaoqing Zhao, Man Hu · 发表于：Drug Resistance Updates · 年份：2025 · DOI：10.1016/j.drup.2025.101202 · 被引用次数：10 · 研究领域：Cancer Immunotherapy and Biomarkers、Glioma Diagnosis and Treatment、Medical Imaging Techniques and Applications

F]AlF-NOTA-PCP2 on PET/CT showed a strong positive correlation with PD-L1 expression by immunohistochemistry (IHC) (R² = 0.861, P < 0.001) in GBM xenograft tumors. The radiotracer uptake in PD-L1-positive tumors significantly increased post-radiotherapy (21.25 ± 0.91 % vs. 25.12 ± 0.82 %, P = 0.008), aligning with the radioresistance observed in these tumors. In vitro studies revealed that PD-L1-driven radioresistance by enhancing DNA damage repair through upregulation of RAD51 after activation of the PI3K-Akt pathway in cells. Preliminary clinical application in a radiotherapy-treated GBM patient demonstrated the ability to monitor PD-L1 dynamics, supporting its potential for clinical translation. Collectively, this peptide-based small molecule PET/CT radiotracers offer a noninvasive, real-time, and quantitative method to dynamically visualize PD-L1-driven radioresistance in GBM. It could serve as a potential radiotracer for facilitating patient stratification, adjusting radiotherapy regimens, and guiding personalized immunotherapy strategies.