Quantitative assessment of Zirconium-89 labeled cetuximab using PET/CT imaging in patients with advanced head and neck cancer: a theragnostic approach.
Quantitative assessment of Zirconium-89 labeled cetuximab using PET/CT imaging in patients with advanced head and neck cancer: a theragnostic approach.
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DOI：
10.18632/oncotarget.13910
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发表时间：
2017-01-17
期刊：
影响因子：
--
通讯作者：
Lambin P
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作者：
Even AJ;Hamming-Vrieze O;van Elmpt W;Winnepenninckx VJ;Heukelom J;Tesselaar ME;Vogel WV;Hoeben A;Zegers CM;Vugts DJ;van Dongen GA;Bartelink H;Mottaghy FM;Hoebers F;Lambin P
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。我们假设肿瘤可及性是EGFR靶向药物治疗成功的重要因素。我们使用PET/CT成像定量用锆-89（89 Zr）标记的西妥昔单抗的摄取。17例III-IV期LAHNSCC患者接受负荷剂量未标记西妥昔单抗，随后接受10 mg 54.5±9.6 MBq 89 Zr-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）和肿瘤与背景比（TBR）定量89 Zr-西妥昔单抗摄取，并与EGFR免疫组织化学相关。比较扫描日之间的TBR以确定最佳时机。患者对89 Zr-西妥昔单抗的摄取不同（第6-7天：SUV峰值范围为2.5-6.2）。TBR在第一次（1.1±0.3）和第二次（1.7±0.6）之间显著增加（49± 28%，p < 0.01）。在EGFR低表达组和高表达组之间，发现SUV平均值（2.1 vs 3.0）和SUV峰值（3.2 vs 4.7）存在显著差异，但TBR无显著差异。数据可在www.cancerdata.org（DOI：10.17195/candat.2016.11.1）获得。总之，89 Zr-西妥昔单抗PET成像显示LAHNSCC患者间差异较大，并提供了FDG-PET和EGFR表达的额外信息。建议使用注射后6-7天获得的扫描来验证预测值。
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.