Immuno-PET imaging for non-invasive assessment of cetuximab accumulation in non-small cell lung cancer
Immuno-PET imaging for non-invasive assessment of cetuximab accumulation in non-small cell lung cancer
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DOI：
10.1186/s12885-019-6238-4
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发表时间：
2019-10-24
期刊：
影响因子：
3.8
通讯作者：
Tsushima, Yoshito
中科院分区：
文献类型：
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作者：
Yamaguchi, Aiko;Achmad, Arifudin;Tsushima, Yoshito
背景过表达表皮生长因子受体（EGFR）已被确定为非小细胞肺癌（NSCLC）的有效治疗靶点。然而，西妥昔单抗作为egfr靶向药物的临床获益仍然存在争议，部分原因是缺乏有效的方法来识别合适的患者。本研究旨在探讨放射标记西妥昔单抗作为一种非侵入性工具的潜力，以预测西妥昔单抗在不同EGFR表达水平的非小细胞肺癌肿瘤异种移植物中的积累。方法注射in -111或cu -64标记的西妥昔单抗48 h后，对非小细胞肺癌模型小鼠肿瘤进行体内生物分布研究和正电子发射断层扫描（PET）成像。体外免疫印迹法检测NSCLC肿瘤中EGFR的表达水平。结果EGFR高表达肿瘤的In-111 - dota -西妥昔单抗蓄积量明显高于EGFR中低表达肿瘤（P < 0.05）。[In-111] in - dota -西妥昔单抗肿瘤摄取与EGFR表达水平呈显著相关性（r = 0.893）， [Cu-64] cu - dota -西妥昔单抗肿瘤摄取与EGFR表达水平呈显著相关性（r = 0.915）。用[Cu-64] cu - dota -西妥昔单抗进行PET成像，肿瘤清晰可见。我们的研究结果表明，这种免疫pet成像可以在临床上转化为预测西妥昔单抗治疗前非小细胞肺癌患者西妥昔单抗积累的工具。
Backgrounds Overexpression of epidermal growth factor receptor (EGFR) has been established as a valid therapeutic target of non-small cell lung cancer (NSCLC). However, the clinical benefit of cetuximab as an EGFR-targeting drug is still controversial, partially due to the lack of effective means to identify suitable patients. This study aimed to investigate the potential of radiolabeled cetuximab as a non-invasive tool to predict cetuximab accumulation in NSCLC tumor xenografts with varying EGFR expression levels. Methods The NSCLC tumors in model mice were subjected to in vivo biodistribution study and positron emission tomography (PET) imaging 48 h after injection of either In-111- or Cu-64-labeled cetuximab. The EGFR expression levels of NSCLC tumors were determined by ex vivo immunoblotting. Results We found that tumors with high EGFR expression had significantly higher [In-111]In-DOTA-cetuximab accumulation than tumors with moderate to low EGFR expression (P < 0.05). Strong correlations were found between [In-111]In-DOTA-cetuximab tumor uptake and EGFR expression level (r = 0.893), and between [Cu-64]Cu-DOTA-cetuximab tumor uptake with EGFR expression level (r = 0.915). PET imaging with [Cu-64]Cu-DOTA-cetuximab allowed clear visualization of tumors. Conclusion Our findings suggest that this immuno-PET imaging can be clinically translated as a tool to predict cetuximab accumulation in NSCLC cancer patients prior to cetuximab therapy.