PET imaging enables direct evaluation of ferroptosis in HCC synergistically induced by anti-PD-L1 and Olaparib
7 affiliations
- 1Department of Nuclear Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- 2Department of Nuclear Medicine, Tongji Hospital, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Huazhong University of Science and Technology, Wuhan, China
- 3Hubei University of Chinese Medicine, Wuhan, Hubei Province China
- 4Hubei Key Laboratory of Resources and Chemistry of Chinese Medicine, Hubei University of Chinese Medicine, Wuhan, Hubei Province China
- 5Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- 6University of Maryland School of Medicine, Baltimore, MD USA
- 7Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Science, Suzhou, China
Abstract
The efficacy of PET image-guided immune checkpoint inhibitor-based therapy in hepatocellular carcinoma (HCC) management is limited by the lack of direct monitoring of therapeutic response. A key challenge is the mismatch between the therapeutic pathway and the imaging target, which hinders the accurate assessment of treatment outcomes. We addressed this challenge by combining anti-PD-L1 immunotherapy with Olaparib, a strategy that promotes ferroptosis in BRCA wild-type HCC by suppressing SLC7A11, thus allowing for therapeutic response evaluation via [18F]FASu PET imaging of SLC7A11 expression. The combination treatment resulted in a 57% reduction in tumor volume, accompanied by decreased Ki-67 expression and increased levels of γ-H2AX and 8-OHdG. [18F]FASu PET imaging revealed significantly lower SUVmax and tumor-to-background ratios in the combination group, correlating with SLC7A11 downregulation. Mechanistically, GPX4 downregulation, glutathione (GSH) depletion and elevated malondialdehyde (MDA) levels confirmed the activation of ferroptosis. Notably, no therapeutic or imaging response was observed in immunodeficient models. Thus, the SLC7A11-targeted PET tracer [18F]FASu offers a clinically translatable biomarker for monitoring treatment efficacy, establishing a novel theragnostic paradigm that directly evaluates treatment response via PET imaging.
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BibTeX
@article{xiong2026imaging,
title = {{PET imaging enables direct evaluation of ferroptosis in HCC synergistically induced by anti-PD-L1 and Olaparib}},
author = {Feng Xiong and Cheng Xu and Pei Wang and Ni Li and Yilin Yang and Buchuan Zhang and Kijung Kwak and Shuang Song and Pengtao You and Xiaohua Zhu and Dalong Ni and Bo Yu},
journal = {Experimental \& Molecular Medicine},
year = {2026},
month = oct,
doi = {10.1038/s12276-026-01860-7},
url = {https://doi.org/10.1038/s12276-026-01860-7},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - PET imaging enables direct evaluation of ferroptosis in HCC synergistically induced by anti-PD-L1 and Olaparib
AU - Feng Xiong
AU - Cheng Xu
AU - Pei Wang
AU - Ni Li
AU - Yilin Yang
AU - Buchuan Zhang
AU - Kijung Kwak
AU - Shuang Song
AU - Pengtao You
AU - Xiaohua Zhu
AU - Dalong Ni
AU - Bo Yu
PY - 2026
DA - 2026/10/09
JO - Experimental & Molecular Medicine
DO - 10.1038/s12276-026-01860-7
UR - https://doi.org/10.1038/s12276-026-01860-7
AB - The efficacy of PET image-guided immune checkpoint inhibitor-based therapy in hepatocellular carcinoma (HCC) management is limited by the lack of direct monitoring of therapeutic response. A key challenge is the mismatch between the therapeutic pathway and the imaging target, which hinders the accurate assessment of treatment outcomes. We addressed this challenge by combining anti-PD-L1 immunotherapy with Olaparib, a strategy that promotes ferroptosis in BRCA wild-type HCC by suppressing SLC7A11, thus allowing for therapeutic response evaluation via [18F]FASu PET imaging of SLC7A11 expression. The combination treatment resulted in a 57% reduction in tumor volume, accompanied by decreased Ki-67 expression and increased levels of γ-H2AX and 8-OHdG. [18F]FASu PET imaging revealed significantly lower SUVmax and tumor-to-background ratios in the combination group, correlating with SLC7A11 downregulation. Mechanistically, GPX4 downregulation, glutathione (GSH) depletion and elevated malondialdehyde (MDA) levels confirmed the activation of ferroptosis. Notably, no therapeutic or imaging response was observed in immunodeficient models. Thus, the SLC7A11-targeted PET tracer [18F]FASu offers a clinically translatable biomarker for monitoring treatment efficacy, establishing a novel theragnostic paradigm that directly evaluates treatment response via PET imaging.
SN - 1226-3613
SN - 2092-6413
ER -