Department of Radiation Oncology, Radboud University Nijmegen Medical Center, The Netherlands; Department of Nuclear Medicine, Radboud University Nijmegen Medical Center, The Netherlands.
Radiother Oncol. 2013 Sep;108(3):484-8. doi: 10.1016/j.radonc.2013.06.034. Epub 2013 Aug 7.
Immunohistochemical epidermal growth factor receptor (EGFR) expression does not correlate with treatment response in head and neck squamous cell carcinomas (HNSCC). Aim was to apply the tracer (111)In-cetuximab-F(ab')2 for EGFR microSPECT imaging and to investigate if tracer uptake correlated with response to EGFR-inhibition by cetuximab in HNSCC xenografts. Usage of F(ab)2 fragments allows for shorter interval between tracer injection and imaging.
Mice with HNSCC xenografts, SCCNij202, 153, 185 and 167 were imaged with microSPECT using (111)In-cetuximab-F(ab')2. Subsequently, tumors were analyzed by autoradiography and immunohistochemistry and tracer concentration was determined. Tumor uptake was correlated with previously assessed response to cetuximab treatment.
MicroSPECT imaging showed preferential uptake in HNSCC xenografts. Tumor-to-liver ratios were 3.1 ± 0.2 (SCCNij202), 2.8 ± 0.4 (SCCNij153), 2.0 ± 0.8 (SCCNij185), 2.0 ± 0.4 (SCCNij167). Immunohistochemical EGFR fractions (fEGFR) differed significantly between xenografts; 0.77 ± 0.07 (SCCNij202), 0.66 ± 0.11 (SCCNij153), 0.57 ± 0.19 (SCCNij185), 0.16 ± 0.10 (SCCNij167) (p < 0.001). Tumor fEGFR correlated with (111)In-cetuximab-F(ab')2 tumor uptake (r = 0.6, p < 0.01) and tracer autoradiography (r = 0.7, p < 0.0001). Tumor uptake of (111)In-cetuximab-F(ab')2 was proportionally associated with cetuximab treatment response in three out of four xenograft models.
(111)In-cetuximab-F(ab')2 showed good tumor-to-background contrast on microSPECT imaging, allowing noninvasive assessment of EGFR expression in vivo, and possibly evaluation of treatment response to EGFR-inhibition.
免疫组织化学表皮生长因子受体（EGFR）表达与头颈部鳞状细胞癌（HNSCC）的治疗反应无关。目的是应用示踪剂（111）In-西妥昔单抗-F（ab'）2 进行 EGFR 微 SPECT 成像，并研究 HNSCC 异种移植中示踪剂摄取与 EGFR 抑制对西妥昔单抗的反应是否相关。使用 F（ab'）2 片段可以在示踪剂注射和成像之间留出更短的间隔。
使用（111）In-西妥昔单抗-F（ab'）2 通过微 SPECT 对具有 HNSCC 异种移植的小鼠进行成像。随后，通过放射自显影和免疫组织化学分析肿瘤，并确定示踪剂浓度。将肿瘤摄取与先前评估的西妥昔单抗治疗反应相关联。
微 SPECT 成像显示 HNSCC 异种移植中优先摄取。肿瘤与肝脏的比值分别为 3.1 ± 0.2（SCCNij202）、2.8 ± 0.4（SCCNij153）、2.0 ± 0.8（SCCNij185）、2.0 ± 0.4（SCCNij167）。异种移植之间的 EGFR 免疫组织化学分数（fEGFR）存在显著差异；0.77 ± 0.07（SCCNij202）、0.66 ± 0.11（SCCNij153）、0.57 ± 0.19（SCCNij185）、0.16 ± 0.10（SCCNij167）（p < 0.001）。肿瘤 fEGFR 与（111）In-西妥昔单抗-F（ab'）2 肿瘤摄取相关（r = 0.6，p < 0.01）和示踪剂放射自显影（r = 0.7，p < 0.0001）。（111）In-西妥昔单抗-F（ab'）2 的肿瘤摄取与四种异种移植模型中的三种西妥昔单抗治疗反应呈比例相关。
（111）In-西妥昔单抗-F（ab'）2 在微 SPECT 成像上显示出良好的肿瘤与背景对比度，允许在体内非侵入性评估 EGFR 表达，并可能评估 EGFR 抑制治疗的反应。
