Zhao Lingzhou, Gong Jiali, Liao Sisi, Huang Wenhua, Zhao Jinhua, Xing Yan
Department of Nuclear Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Hongkou District, No. 100, Haining Road, Shanghai, 200080, China.
Nanomab Technology Limited, No. 333, North Chengdu Road, Jingan District, Shanghai, 200041, China.
Cancer Imaging. 2025 Jan 27;25(1):6. doi: 10.1186/s40644-025-00826-8.
Programmed cell death 1/programmed death ligand-1 (PD-L1)-based immune checkpoint blockade is an effective treatment approach for non-small-cell lung cancer (NSCLC). However, immunohistochemistry does not accurately or dynamically reflect PD-L1 expression owing to its spatiotemporal heterogeneity. Herein, we assessed the feasibility of using a Ga-labeled anti-PD-L1 nanobody, Ga-NODAGA-NM-01, for PET imaging of PD-L1.
Micro-PET/CT and biodistribution studies were performed on PD-L1-positive and -negative tumor-bearing mice. Additionally, a preliminary clinical study was performed on two patients with NSCLC. NM-01 was radiolabeled with Ga without further purification under mild conditions.
Ga-NODAGA-NM-01 exhibited radiochemical purity (> 98%), high stability in vitro, and rapid blood clearance in vivo. Specific accumulation of Ga-NODAGA-NM-01 was observed in PD-L1-positive tumor-bearing mice, with a good tumor-to-background ratio 0.5h post-injection. Furthermore, Ga-NODAGA-NM-01 PET/CT imaging was found to be safe with no adverse events and distinct uptake in primary and metastatic lesions of the PD-L1-positive patient, with a higher maximal standardized uptake value than that in lesions of the PD-L1-negative patient 1h post-injection.
Ga-NODAGA-NM-01 can be prepared using a simple method under mild conditions and reflect PD-L1 expression in primary and metastatic lesions. However, our findings need to be confirmed in a large cohort.
NCT02978196. Registered February 15, 2018.
基于程序性细胞死亡蛋白1/程序性死亡配体1（PD-L1）的免疫检查点阻断是治疗非小细胞肺癌（NSCLC）的一种有效方法。然而，由于其时空异质性，免疫组化不能准确或动态地反映PD-L1的表达。在此，我们评估了使用镓标记的抗PD-L1纳米抗体Ga-NODAGA-NM-01进行PD-L1正电子发射断层扫描（PET）成像的可行性。
对携带PD-L1阳性和阴性肿瘤的小鼠进行微型PET/CT和生物分布研究。此外，对两名NSCLC患者进行了初步临床研究。在温和条件下，无需进一步纯化，用镓对NM-01进行放射性标记。
Ga-NODAGA-NM-01表现出放射化学纯度（>98%）、体外高稳定性和体内快速血液清除率。在携带PD-L1阳性肿瘤的小鼠中观察到Ga-NODAGA-NM-01的特异性蓄积，注射后0.5小时肿瘤与本底比值良好。此外，发现Ga-NODAGA-NM-01 PET/CT成像安全，无不良事件，在PD-L1阳性患者的原发和转移病灶中有明显摄取，注射后1小时最大标准化摄取值高于PD-L1阴性患者的病灶。
Ga-NODAGA-NM-01可以在温和条件下用简单方法制备，并能反映原发和转移病灶中的PD-L1表达。然而，我们的研究结果需要在大型队列中得到证实。
NCT02978196。2018年2月15日注册。
