Wang Yong, He Kewen, Zhang Yang, Chen Yunhao, Wang Shijie, Zhao Kunlong, Liu Zhiguo, Hu Man
Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, China.
Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical Sciences, Jinan, 250117, China.
J Pharm Anal. 2025 Mar;15(3):101082. doi: 10.1016/j.jpha.2024.101082. Epub 2024 Aug 26.
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 [F]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. [F]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 and , with a dissociation constant of 0.24 nM. PET/CT imaging, integrated with contrast-enhanced magnetic resonance imaging, revealed significant accumulation of [F]AlF-NOTA-PCP2 in orthotopic tumors, correlating with blood-brain barrier disruption. After radiotherapy (15 Gy), [F]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, [F]AlF-NOTA-PCP2 may be a valuable tool for noninvasively monitoring PD-L1 expression in brain tumors after radiotherapy.
使用分子成像进行实时、无创程序性死亡配体1（PD-L1）检测，加深了我们对肿瘤免疫环境的理解，并为免疫治疗提供了指导。然而，正电子发射断层扫描/计算机断层扫描（PET/CT）放射性示踪剂在人脑肿瘤成像中的应用仍然有限。本研究涉及[F]AlF-NOTA-PCP2的合成，这是一种新型的基于肽的放射性标记示踪剂，可靶向PD-L1，并评估其在原位胶质母细胞瘤（GBM）模型中的成像能力。使用这种示踪剂，我们可以无创监测GBM中辐射诱导的PD-L1变化。[F]AlF-NOTA-PCP2表现出高放射化学纯度（>95%），合成后4小时内稳定性良好。它显示出与PD-L1的特异性、高亲和力结合，解离常数为0.24 nM。PET/CT成像与对比增强磁共振成像相结合，显示[F]AlF-NOTA-PCP2在原位肿瘤中有显著积聚，与血脑屏障破坏相关。放疗（15 Gy）后，肿瘤对[F]AlF-NOTA-PCP2的摄取从9.51%±0.73%增加到12.04%±1.43%，表明PD-L1表达增强，与免疫组化结果一致。与单次剂量（11.48%±1.05% ID/cc）相比，分次放疗（5 Gy×3）进一步放大了PD-L1上调（13.9%±1.54% ID/cc）。综上所述，[F]AlF-NOTA-PCP2可能是一种无创监测放疗后脑肿瘤中PD-L1表达的有价值工具。
