68Ga-NK224 PET/CT揭示非小细胞肺癌中PD-L1的瘤内和瘤间异质性
68Ga-NK224 PET/CT Reveals Intra- and Intertumoral Heterogeneity of PD-L1 in Non-Small Cell Lung Cancer.
作者
作者单位
- Department of Nuclear Medicine and Minnan PET Center, Xiamen Key Laboratory of Radiopharmaceuticals, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, 55 Zhenhai Rd, Xiamen 361003, China.
- Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China.
- Department of Medical Oncology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
摘要
中文
背景：程序性死亡配体1（PD-L1）表达通过单点活检的免疫组织化学分析评估是指导非小细胞肺癌（NSCLC）免疫治疗的标准方法。然而，这种方法未能捕获瘤内和瘤间异质性。目的：研究镓68（68Ga）NK224 PET/CT是否能够实现NSCLC中PD-L1表达和异质性的全身评估，以及病变特异性治疗反应是否与PET定义的PD-L1摄取相关。材料与方法：在这项于2023年12月至2025年7月进行的前瞻性研究中，新诊断或复发或转移性NSCLC的参与者接受了68Ga-NK224 PET/CT和PD-L1免疫组织化学分析。使用来自活检平面感兴趣区（ROIs）和全病灶ROIs的最大标准化摄取值（SUVmax）量化肿瘤对68Ga-NK224的摄取。PD-L1肿瘤比例评分（TPS）作为参考标准。使用SUVmax的归一化范围评估瘤内异质性，并使用跨病灶的SUVmax变异系数评估瘤间异质性。结果：本研究纳入48名参与者（中位年龄，68岁[IQR，59-75岁]；31名男性）。在52个病灶中，68Ga-NK224摄取在不同PD-L1 TPS类别间存在差异（P < .001），活检平面SUVmax与TPS强相关（Spearman ρ = 0.80；P < .001）。接受者操作特征分析确定了区分高PD-L1表达肿瘤的最佳SUVmax截断值为5.6。在12名通过免疫组织化学分析分类为PD-L1阴性的参与者中，5名有一个或多个病灶的SUVmax高于截断值（68个病灶中的15个）。使用全病灶ROIs评估的瘤内异质性（中位归一化范围，1.0）显著高于活检平面ROIs（中位归一化范围，0.4）（P < .001）。个体参与者内的瘤间异质性显著（中位SUVmax变异系数，23.6% [IQR，17.9%-36.7%]）。在接受免疫治疗的参与者中（24个病灶），部分或完全反应（缩小≥30%；中位缩小，47.5%）的病灶显示出比进展或稳定疾病（缩小<30%；中位缩小，7.4%）更大的68Ga-NK224摄取（中位SUVmax，5.9 vs 1.9；P = .01）。结论：68Ga-NK224 PET/CT能够实现NSCLC中PD-L1异质性的全身评估，并揭示了活检无法捕获的病灶水平异质性，且摄取与免疫治疗反应相关。临床试验注册号：NCT06754345 © 作者2026年。由北美放射学会根据CC BY 4.0许可证发布。本文提供补充材料。另见本期Lopci的社论。
English
Background Programmed death ligand 1 (PD-L1) expression assessed via immunohistochemical analysis of single-site biopsies is standard for guiding immunotherapy in non-small cell lung cancer (NSCLC). However, this approach fails to capture intra- and intertumoral heterogeneity. Purpose To investigate whether gallium 68 (68Ga) NK224 PET/CT enables whole-body assessment of PD-L1 expression and heterogeneity in NSCLC and whether lesion-specific treatment response is associated with PET-defined PD-L1 uptake. Materials and Methods In this prospective study conducted from December 2023 to July 2025, participants with newly diagnosed or recurrent or metastatic NSCLC underwent 68Ga-NK224 PET/CT and PD-L1 immunohistochemical analysis. Tumor uptake of 68Ga-NK224 was quantified using maximum standardized uptake value (SUVmax) from biopsy-plane regions of interest (ROIs) and whole-lesion ROIs. PD-L1 tumor proportion score (TPS) was the reference standard. Intratumoral heterogeneity was assessed using the normalized range of SUVmax, and intertumoral heterogeneity was evaluated using the SUVmax coefficient of variation across lesions. Results This study included 48 participants (median age, 68 years [IQR, 59-75 years]; 31 men). Across 52 lesions, 68Ga-NK224 uptake differed among PD-L1 TPS categories (P < .001), and biopsy-plane SUVmax correlated strongly with TPS (Spearman ρ = 0.80; P < .001). Receiver operating characteristic analysis identified an optimal SUVmax cutoff of 5.6 for discriminating tumors with high PD-L1 expression. Among 12 participants classified as PD-L1 negative via immunohistochemical analysis, five had one or more lesions with SUVmax above the cutoff (15 of 68 lesions). Intratumoral heterogeneity was substantially higher when assessed using whole-lesion ROIs (median normalized range, 1.0) versus biopsy-plane ROIs (median normalized range, 0.4) (P < .001). Intertumoral heterogeneity within individual participants was pronounced (median SUVmax coefficient of variation, 23.6% [IQR, 17.9%-36.7%]). In participants receiving immunotherapy (24 lesions), lesions with partial or complete response (shrinkage ≥30%; median shrinkage, 47.5%) showed greater 68Ga-NK224 uptake than lesions with progressive or stable disease (shrinkage <30%; median shrinkage, 7.4%) (median SUVmax, 5.9 vs 1.9; P = .01). Conclusion 68Ga-NK224 PET/CT enabled whole-body assessment of PD-L1 heterogeneity in NSCLC and revealed lesion-level heterogeneity not captured through biopsy, and uptake was associated with immunotherapy response. Clinical trial registration no. NCT06754345 © The Author(s) 2026. Published by the Radiological Society of North America under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Lopci in this issue.
分类与指标
- 研究类型
- 临床研究
- 病种
- 肺癌
- JCR 分区
- Q1
- 影响因子
- 17.6
- 新锐分区
- 1区