PET imaging biomarkers of anti-EGFR immunotherapy in esophageal squamous cell carcinoma models

Epidermal growth factor receptor (EGFR) is overexpressed and considered as a proper molecular target for diagnosis and targeted therapy of esophageal squamous cell carcinoma (ESCC). This study evaluated the usefulness of PET imaging biomarkers with ⁶⁴ Cu-PCTA-cetuximab and ¹⁸ F-FDG-PET for anti-EGFR immunotherapy in ESCC models. In vivo EGFR status and glucose metabolism by cetuximab treatment were evaluated using ⁶⁴ Cu-PCTA-cetuximab and ¹⁸ F-FDG-PET, respectively. Therapeutic responses with imaging biomarkers were confirmed by western blot and immunohistochemistry. TE-4 and TE-8 tumors were clearly visualized by ⁶⁴ Cu-PCTA-cetuximab, and EGFR expression on TE-8 tumors showed 2.6-fold higher uptake than TE-4. Tumor volumes were markedly reduced by cetuximab in TE-8 tumor (92.5 ± 5.9%), but TE-4 tumors were refractory to cetuximab treatment. The SUVs in ⁶⁴ Cu-PCTA-cetuximab and ¹⁸ F-FDG-PET images were statistically significantly reduced by cetuximab treatment in TE-8 but not in TE-4. ⁶⁴ Cu-PCTA-cetuximab and ¹⁸ F-FDG-PET images were well correlated with EGFR and pAkt levels. ⁶⁴ Cu-PCTA-cetuximab immuno-PET had a potential for determining EGFR level and monitoring therapeutic response by anti-EGFR therapy. ¹⁸ F-FDG-PET was also attractive for monitoring efficacy of anti-EGFR therapy. In conclusion, PET imaging biomarkers may be useful for selecting patients that express target molecules and for monitoring therapeutic efficacy of EGFR-targeted therapy in ESCC patients.