¹¹¹In-cetuximab-F(ab鈥?₂ SPECT imaging for quantification of accessible epidermal growth factor receptors (EGFR) in HNSCC xenografts

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• 作者：Laura K. van Dijk ; Bianca A.W. Hoeben ; Hanneke Stegeman ; Johannes H.A.M. Ka ; ers ; Gerben M. Franssen ; Otto C. Boerman ; Johan Bussink
• 关键词：Head and neck cancer ; EGFR imaging ; Cetuximab ; SPECT ; Preclinical
• 刊名：Radiotherapy and Oncology
• 出版年：September, 2013
• 年：2013
• 卷：108
• 期：3
• 页码：484-488
• 全文大小：880 K

文摘

Background and purpose

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 ¹¹¹In-cetuximab-F(ab鈥?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.

Materials and methods

Mice with HNSCC xenografts, SCCNij202, 153, 185 and 167 were imaged with microSPECT using ¹¹¹In-cetuximab-F(ab鈥?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.

Results

MicroSPECT imaging showed preferential uptake in HNSCC xenografts. Tumor-to-liver ratios were 3.1 卤 0.2 (SCCNij202), 2.8 卤 0.4 (SCCNij153), 2.0 卤 0.8 (SCCNij185), 2.0 卤 0.4 (SCCNij167). Immunohistochemical EGFR fractions (fEGFR) differed significantly between xenografts; 0.77 卤 0.07 (SCCNij202), 0.66 卤 0.11 (SCCNij153), 0.57 卤 0.19 (SCCNij185), 0.16 卤 0.10 (SCCNij167) (p < 0.001). Tumor fEGFR correlated with ¹¹¹In-cetuximab-F(ab鈥?₂ tumor uptake (r = 0.6, p < 0.01) and tracer autoradiography (r = 0.7, p < 0.0001). Tumor uptake of ¹¹¹In-cetuximab-F(ab鈥?₂ was proportionally associated with cetuximab treatment response in three out of four xenograft models.

Conclusion

¹¹¹In-cetuximab-F(ab鈥?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.