Department of Radiation Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.
Front Endocrinol (Lausanne). 2022 Jun 30;13:913631. doi: 10.3389/fendo.2022.913631. eCollection 2022.
We investigated the correlation of F-AlF-NOTAPRGD2 (F-RGD) uptake during positron emission tomography (PET) with tumoral programmed death-ligand 1 (PD-L1) expression and explored its potential in immune checkpoint inhibitor treatment.
Forty-two mice were subcutaneously injected with CMT-167 lung carcinoma cells. A total of 30 mice with good growth tumor and good general condition were selected. F-RGD PET scanning was performed on days 0, 2, 4, 6, 9, and 11 with five mice per day. Immunohistochemistry (IHC) for PD-L1 was performed on each specimen obtained from tumors. Thirty patients with advanced non-small cell lung cancer (NSCLC) were scanned using F-RGD PET/CT, and Milliplex multifactor detection analyzed serum PD-1/PD-L1 expression of twenty-eight of them. Thirteen of them were analyzed immunohistochemically using core needle biopsy samples obtained from primary tumors.
Thirty mice were scanned by F-RGD PET/CT and analyzed for PD-L1 expression in tumor cells by IHC finally. Maximum standard uptake value (SUVmax) and mean SUV (SUVmean) were significantly lower in relatively-higher-PD-L1-expression tumors than in relatively-low-PD-L1-expression tumors (P < 0.05). In patients, the SUVmax was significantly negatively correlated with tumoral PD-L1 expression by IHC (P=0.014). SUVmean, peak SUV (SUVpeak), and gross tumor volume (GTV) were also negatively correlated with PD-L1, but without significance (P > 0.05). SUVmax, SUVmean, SUVpeak, and GTV were negatively correlated with serum PD-1 and PD-L1, but not significantly. According to the receiver operating characteristic curve analysis, significant correlations between SUVmax and tumoral PD-L1 expression in both mice and patients were present (P < 0.05).
Higher F-RGD uptake is correlated with depressed PD-L1 expression in tumor cells, and SUVmax is the best parameter to display tumoral expression of PD-L1. F-RGD PET may be useful for reflecting the immune status of NSCLC.
我们研究了正电子发射断层扫描（PET）期间 F-AlF-NOTAPRGD2（F-RGD）摄取与肿瘤程序性死亡配体 1（PD-L1）表达的相关性，并探讨了其在免疫检查点抑制剂治疗中的潜力。
42 只小鼠皮下注射 CMT-167 肺癌细胞。选择 30 只肿瘤生长良好、一般状况良好的小鼠。每天每只小鼠进行 5 次 F-RGD PET 扫描，共 11 天。对每个肿瘤标本进行 PD-L1 免疫组化（IHC）检测。对 30 名晚期非小细胞肺癌（NSCLC）患者进行 F-RGD PET/CT 扫描，对其中 28 名患者的血清 PD-1/PD-L1 表达进行了 Milliplex 多因子检测分析。其中 13 名患者采用原发性肿瘤获得的核心针活检样本进行免疫组化分析。
30 只小鼠进行了 F-RGD PET/CT 扫描，最终通过 IHC 分析肿瘤细胞中的 PD-L1 表达。相对高 PD-L1 表达肿瘤的最大标准摄取值（SUVmax）和平均 SUV（SUVmean）明显低于相对低 PD-L1 表达肿瘤（P<0.05）。在患者中，SUVmax 与 IHC 检测到的肿瘤 PD-L1 表达呈显著负相关（P=0.014）。SUVmean、SUVpeak 和大体肿瘤体积（GTV）也与 PD-L1 呈负相关，但无统计学意义（P>0.05）。SUVmax、SUVmean、SUVpeak 和 GTV 与血清 PD-1 和 PD-L1 呈负相关，但无统计学意义。根据受试者工作特征曲线分析，小鼠和患者中 SUVmax 与肿瘤 PD-L1 表达之间存在显著相关性（P<0.05）。
较高的 F-RGD 摄取与肿瘤细胞中 PD-L1 表达下调相关，SUVmax 是显示肿瘤 PD-L1 表达的最佳参数。F-RGD PET 可能有助于反映 NSCLC 的免疫状态。
