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.

Abstract

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 (111)In-cetuximab-F(ab')2 SPECT before and after radiotherapy, while simultaneously evaluating (18)F-FDG PET uptake. Mice with HNSCC xenografts, cetuximab-sensitive SCCNij202 and cetuximab-resistant SCCNij167, were imaged with SPECT/CT using (111)In-cetuximab-F(ab')2 as a tracer, directly followed by PET imaging with (18)F-FDG. Scans were acquired 7 d before radiotherapy (10 Gy) and 1, 7, and 14 d after treatment. Intratumoral localization of (111)In-cetuximab-F(ab')(2) was evaluated by autoradiography and histologic markers evaluated by immunofluorescence staining in the same tumor sections. Growth of irradiated SCCNij202 and SCCNij167 tumors was significantly delayed, compared with controls (P < 0.05). No changes in uptake of (18)F-FDG were observed in either of the xenografts after radiotherapy. SPECT images of tumor-bearing mice showed a significant increase in uptake of (111)In-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 (111)In-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). EGFR accessibility can be visualized with (111)In-cetuximab-F(ab')(2). (111)In-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.