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

Journal of Nuclear Medicine

Jasper Lok¹  Gerben M. Franssen¹  Johannes H.A.M. Kaanders¹  Laura K. van Dijk¹  Johan Bussink¹  Otto C. Boerman¹ 

关键词: EGFR;    SPECT;    PET;    radiotherapy;    HNSCC;   

DOI  :  10.2967/jnumed.114.141762

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

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.

【 授权许可】

Unknown