Even Aniek J G, Hamming-Vrieze Olga, van Elmpt Wouter, Winnepenninckx Véronique J L, Heukelom Jolien, Tesselaar Margot E T, Vogel Wouter V, Hoeben Ann, Zegers Catharina M L, Vugts Daniëlle J, van Dongen Guus A M S, Bartelink Harry, Mottaghy Felix M, Hoebers Frank, Lambin Philippe
Department of Radiation Oncology (MAASTRO), GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands.
Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Oncotarget. 2017 Jan 17;8(3):3870-3880. doi: 10.18632/oncotarget.13910.
Biomarkers predicting treatment response to the monoclonal antibody cetuximab in locally advanced head and neck squamous cell carcinomas (LAHNSCC) are lacking. We hypothesize that tumor accessibility is an important factor in treatment success of the EGFR targeting drug. We quantified uptake of cetuximab labeled with Zirconium-89 (89Zr) using PET/CT imaging.Seventeen patients with stage III-IV LAHNSCC received a loading dose unlabeled cetuximab, followed by 10 mg 54.5±9.6 MBq 89Zr-cetuximab. PET/CT images were acquired either 3 and 6 or 4 and 7 days post-injection. 89Zr-cetuximab uptake was quantified using standardized uptake value (SUV) and tumor-to-background ratio (TBR), and correlated to EGFR immunohistochemistry. TBR was compared between scan days to determine optimal timing.Uptake of 89Zr-cetuximab varied between patients (day 6-7: SUVpeak range 2.5-6.2). TBR increased significantly (49±28%, p < 0.01) between first (1.1±0.3) and second scan (1.7±0.6). Between groups with a low and high EGFR expression a significant difference in SUVmean (2.1 versus 3.0) and SUVpeak (3.2 versus 4.7) was found, however, not in TBR. Data is available at www.cancerdata.org (DOI: 10.17195/candat.2016.11.1).In conclusion, 89Zr-cetuximab PET imaging shows large inter-patient variety in LAHNSCC and provides additional information over FDG-PET and EGFR expression. Validation of the predictive value is recommended with scans acquired 6-7 days post-injection.
目前尚缺乏预测局部晚期头颈部鳞状细胞癌（LAHNSCC）对单克隆抗体西妥昔单抗治疗反应的生物标志物。我们推测肿瘤可及性是表皮生长因子受体（EGFR）靶向药物治疗成功的一个重要因素。我们使用正电子发射断层扫描/计算机断层扫描（PET/CT）成像对用锆-89（89Zr）标记的西妥昔单抗摄取情况进行了量化。17例III-IV期LAHNSCC患者先接受了一剂未标记的西妥昔单抗负荷剂量，随后接受10mg 54.5±9.6MBq的89Zr-西妥昔单抗。在注射后3天和6天或4天和7天采集PET/CT图像。使用标准化摄取值（SUV）和肿瘤与本底比值（TBR）对89Zr-西妥昔单抗摄取情况进行量化，并与EGFR免疫组化结果相关联。比较不同扫描日的TBR以确定最佳扫描时间。89Zr-西妥昔单抗的摄取情况在患者之间存在差异（第6-7天：SUV峰值范围为2.5-6.2）。第一次扫描时TBR为1.1±0.3，第二次扫描时显著增加（49±28%，p<0.01）至1.7±0.6。在EGFR低表达组和高表达组之间，SUV平均值（2.1对3.0）和SUV峰值（3.2对4.7）存在显著差异，但TBR无显著差异。数据可在www.cancerdata.org获取（DOI：10.17195/candat.2016.11.1）。总之，89Zr-西妥昔单抗PET成像显示LAHNSCC患者之间存在很大差异，并提供了超过氟代脱氧葡萄糖（FDG）-PET和EGFR表达的额外信息。建议在注射后6-7天进行扫描以验证其预测价值。
