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Cells. 2018 Oct 27;7(11). pii: E187. doi: 10.3390/cells7110187.

PET Imaging Biomarkers of Anti-EGFR Immunotherapy in Esophageal Squamous Cell Carcinoma Models.

Author information

1
Division of RI Application, Korea Institute of Radiological and Medical Sciences (KIRAMS), Seoul 01812, Korea. nobelcow@kirams.re.kr.
2
Division of RI Application, Korea Institute of Radiological and Medical Sciences (KIRAMS), Seoul 01812, Korea. inosong@naver.com.
3
Division of RI Application, Korea Institute of Radiological and Medical Sciences (KIRAMS), Seoul 01812, Korea. shinjongil@kirams.re.kr.
4
Department of Biomedical Laboratory Science, College of Health Science, Yonsei University, Wonju 26493, Korea. parkys@yonsei.ac.kr.
5
Division of RI Application, Korea Institute of Radiological and Medical Sciences (KIRAMS), Seoul 01812, Korea. jykim@kirams.re.kr.
6
Division of RI Application, Korea Institute of Radiological and Medical Sciences (KIRAMS), Seoul 01812, Korea. kikim@kirams.re.kr.
7
Division of RI Application, Korea Institute of Radiological and Medical Sciences (KIRAMS), Seoul 01812, Korea. yjlee@kirams.re.kr.
8
Division of RI Application, Korea Institute of Radiological and Medical Sciences (KIRAMS), Seoul 01812, Korea. kang2325@kirams.re.kr.

Abstract

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 64Cu-PCTA-cetuximab and 18F-FDG-PET for anti-EGFR immunotherapy in ESCC models. In vivo EGFR status and glucose metabolism by cetuximab treatment were evaluated using 64Cu-PCTA-cetuximab and 18F-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 64Cu-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 64Cu-PCTA-cetuximab and 18F-FDG-PET images were statistically significantly reduced by cetuximab treatment in TE-8 but not in TE-4. 64Cu-PCTA-cetuximab and 18F-FDG-PET images were well correlated with EGFR and pAkt levels. 64Cu-PCTA-cetuximab immuno-PET had a potential for determining EGFR level and monitoring therapeutic response by anti-EGFR therapy. 18F-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.

KEYWORDS:

18F-FDG; Cu-64; EGFR; PET; cetuximab; imaging biomarker

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