Peptide-based immuno-PET/CT monitoring of dynamic PD-L1 expression during glioblastoma radiotherapy

Yong Wang; Kewen He; Yang Zhang; Yunhao Chen; Shijie Wang; Kunlong Zhao; Zhiguo Liu; Man Hu

doi:10.1016/j.jpha.2024.101082

Volume 15 Issue 3

Apr. 2025

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Yong Wang, Kewen He, Yang Zhang, Yunhao Chen, Shijie Wang, Kunlong Zhao, Zhiguo Liu, Man Hu. Peptide-based immuno-PET/CT monitoring of dynamic PD-L1 expression during glioblastoma radiotherapy[J]. Journal of Pharmaceutical Analysis, 2025, 15(3): 101082. doi: 10.1016/j.jpha.2024.101082

Citation:

Yong Wang, Kewen He, Yang Zhang, Yunhao Chen, Shijie Wang, Kunlong Zhao, Zhiguo Liu, Man Hu. Peptide-based immuno-PET/CT monitoring of dynamic PD-L1 expression during glioblastoma radiotherapy[J]. Journal of Pharmaceutical Analysis, 2025, 15(3): 101082. doi: 10.1016/j.jpha.2024.101082

Citation:

Yong Wang, Kewen He, Yang Zhang, Yunhao Chen, Shijie Wang, Kunlong Zhao, Zhiguo Liu, Man Hu. Peptide-based immuno-PET/CT monitoring of dynamic PD-L1 expression during glioblastoma radiotherapy[J]. Journal of Pharmaceutical Analysis, 2025, 15(3): 101082. doi: 10.1016/j.jpha.2024.101082

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Peptide-based immuno-PET/CT monitoring of dynamic PD-L1 expression during glioblastoma radiotherapy

doi: 10.1016/j.jpha.2024.101082

a. Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, China;
b. Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical Sciences, Jinan, 250117, China;
c. Department of PET/CT Center, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical Sciences, Jinan, 250117, China

Funds:

This study received support from the National Natural Science Foundation of China (Grant Nos.: 82272751 and 82202958), the Natural Science Foundation of Shandong, China (Grant No.: ZR2021LSW002), and the Science and Technology Program of Jinan, China (Grant Nos.: 202225019 and 202225013) to Man Hu

the Shandong Postdoctoral Innovation Program, China (Grant No.: SDCX-ZG-202302011) and Beijing Science and Technology Innovation Medical Development Foundation, China (Grant No.: KC2023-JX-0288-BQ26) to Yong Wang

the Natural Science Foundation of China (Grant No.: NSFC82303676), the Natural Science Foundation of Shandong (Grant No.: ZR2023QH208), the China Postdoctoral Science Foundation (Grant No.: 2023M732125), and the Taishan Scholar Project Special Fund (Grant No.: tsqn202312368) to Kewen He.

Received Date: Apr. 08, 2024
Accepted Date: Aug. 21, 2024
Rev Recd Date: Aug. 17, 2024
Publish Date: Aug. 26, 2024

Abstract

Abstract

Real-time, noninvasive programmed death-ligand 1 (PD-L1) testing using molecular imaging has enhanced our understanding of the immune environments of neoplasms and has served as a guide for immunotherapy. However, the utilization of radiotracers in the imaging of human brain tumors using positron emission tomography/computed tomography (PET/CT) remains limited. This investigation involved the synthesis of [¹⁸F]AlF-NOTA-PCP2, which is a novel peptide-based radiolabeled tracer that targets PD-L1, and evaluated its imaging capabilities in orthotopic glioblastoma (GBM) models. Using this tracer, we could noninvasively monitor radiation-induced PD-L1 changes in GBM. [¹⁸F]AlF-NOTA-PCP2 exhibited high radiochemical purity (>95%) and stability up to 4 h after synthesis. It demonstrated specific, high-affinity binding to PD-L1 in vitro and in vivo, with a dissociation constant of 0.24 nM. PET/CT imaging, integrated with contrast-enhanced magnetic resonance imaging, revealed significant accumulation of [¹⁸F]AlF-NOTA-PCP2 in orthotopic tumors, correlating with blood-brain barrier disruption. After radiotherapy (15 Gy), [¹⁸F]AlF-NOTA-PCP2 uptake in tumors increased from 9.51% ± 0.73% to 12.04% ± 1.43%, indicating enhanced PD-L1 expression consistent with immunohistochemistry findings. Fractionated radiation (5 Gy × 3) further amplified PD-L1 upregulation (13.9% ± 1.54% ID/cc) compared with a single dose (11.48% ± 1.05% ID/cc). Taken together, [¹⁸F]AlF-NOTA-PCP2 may be a valuable tool for noninvasively monitoring PD-L1 expression in brain tumors after radiotherapy.
- PET/CT,
- Cyclic peptide,
- PD-L1,
- Glioblastoma,
- Radiotherapy

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References(47)

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