Early Response Monitoring with 18F-FDG PET and Cetuximab-F(ab′)2-SPECT After Radiotherapy of Human Head and Neck Squamous Cell Carcinomas in a Mouse Model
Early Response Monitoring with 18F-FDG PET and Cetuximab-F(ab′)2-SPECT After Radiotherapy of Human Head and Neck Squamous Cell Carcinomas in a Mouse Model
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DOI：
10.2967/jnumed.114.141762
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发表时间：
2014-10
期刊：
影响因子：
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通讯作者：
Laura K. van Dijk;O. Boerman;G. Franssen;J. Lok;J. Kaanders;J. Bussink
中科院分区：
文献类型：
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作者：
Laura K. van Dijk;O. Boerman;G. Franssen;J. Lok;J. Kaanders;J. Bussink
只有一小部分头颈部鳞状细胞癌(HNSCCs)患者从放射治疗和同时使用西妥昔单抗的表皮生长因子受体(EGFR)抑制剂治疗中受益，这表明需要选择患者。这项研究的目的是通过111In-西妥昔单抗-F(ab‘)2 SPECT观察放射治疗前后系统可达的EGFR的变化，同时评估18F-FDG的PET摄取。方法：以111In-西妥昔单抗-F(ab‘)2为示踪剂，对西妥昔单抗敏感的SCCNij202和耐药的SCCNij167移植HNSCC小鼠进行SPECT/CT显像，然后用18F-FDG进行PET显像。分别于放疗前7d、治疗后1d、7d、14d进行扫描。111In-西妥昔单抗F(ab‘)2的瘤内定位采用放射自显影，组织学标志物采用免疫荧光染色。结果：照射后的SCCNij202和SCCNij167肿瘤生长明显延缓(P<；0.05)。放射治疗后，两种移植瘤对18F-FDG的摄取均未见改变。荷瘤小鼠的SPECT图像显示，照射后SCCNij202肿瘤对111In-西妥昔单抗-F(ab‘)2的摄取显著增加(治疗前7d和14d，肿瘤与肝脏的比率分别为4.3±1.1和10.5±3.3，P<；0.01)，而在SCCNij167肿瘤中没有明显的摄取。免疫组织化学EGFR染色显示照射后的SCCNij202移植瘤中EGFR从胞浆移位到细胞膜。放射自显影测定的111In-西妥昔单抗F(ab‘)2在肿瘤内的分布与免疫组织化学测定的EGFR分布有很好的相关性(r=0.85；范围0.69-0.95)。结论：111In-西妥昔单抗-F(ab‘)2可以显示EGFR的可达性。111In-西妥昔单抗-F(ab’)2仅在对西妥昔单抗敏感的SCCNij202移植瘤中摄取增加，提示该示踪剂可用于测量放疗诱导的EGFR表达的变化，并可监测肿瘤对放射治疗的代偿反应。
Only a subset of patients with head and neck squamous cell carcinomas (HNSCCs) benefit from radiotherapy and concurrent epidermal growth factor receptor (EGFR) inhibitor therapy with cetuximab, indicating the need for patient selection. The aim of this study was to visualize the change in systemically accessible EGFR with 111In-cetuximab-F(ab′)2 SPECT before and after radiotherapy, while simultaneously evaluating 18F-FDG PET uptake. Methods: Mice with HNSCC xenografts, cetuximab-sensitive SCCNij202 and cetuximab-resistant SCCNij167, were imaged with SPECT/CT using 111In-cetuximab-F(ab′)2 as a tracer, directly followed by PET imaging with 18F-FDG. Scans were acquired 7 d before radiotherapy (10 Gy) and 1, 7, and 14 d after treatment. Intratumoral localization of 111In-cetuximab-F(ab′)2 was evaluated by autoradiography and histologic markers evaluated by immunofluorescence staining in the same tumor sections. Results: Growth of irradiated SCCNij202 and SCCNij167 tumors was significantly delayed, compared with controls (P < 0.05). No changes in uptake of 18F-FDG were observed in either of the xenografts after radiotherapy. SPECT images of tumor-bearing mice showed a significant increase in uptake of 111In-cetuximab-F(ab′)2 in the SCCNij202 tumors after irradiation (tumor-to-liver ratio, 4.3 ± 1.1 vs. 10.5 ± 3.3, 7 d before and 14 d after treatment, respectively, P < 0.01) but not in SCCNij167 tumors. Immunohistochemical EGFR staining showed a translocation of the EGFR from the cytoplasm to the cell membrane in irradiated SCCNij202 xenografts. Intratumoral distribution of 111In-cetuximab-F(ab′)2 as determined by autoradiography correlated well with the distribution of EGFR as determined immunohistochemically (r = 0.85; range, 0.69–0.95). Conclusion: EGFR accessibility can be visualized with 111In-cetuximab-F(ab′)2. 111In-cetuximab-F(ab′)2 uptake increased after irradiation only in cetuximab-sensitive SCCNij202 xenografts, implying that the tracer can be used to measure irradiation-induced changes of EGFR expression and can monitor the compensatory response of tumors to radiotherapy.