18F-fluorodeoxyglucose uptake predicts MET expression in lung adenocarcinoma

Shuxian An; Xiang Zhou; Jianjun Liu; Gang Huang

doi:10.2147/OTT.S150334

¹⁸F-fluorodeoxyglucose uptake predicts MET expression in lung adenocarcinoma

Onco Targets Ther. 2017 Nov 27:10:5643-5651. doi: 10.2147/OTT.S150334. eCollection 2017.

Authors

Shuxian An^#^{1

2}, Xiang Zhou^#^{1

2}, Jianjun Liu^{1

2}, Gang Huang^{1

2

3

4}

Affiliations

¹ Department of Nuclear Medicine.
² Institute of Clinical Nuclear Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University.
³ Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine and Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences.
⁴ Shanghai University of Medicine and Health Sciences, Shanghai, China.

^# Contributed equally.

Abstract

Objective: MET is a member of the receptor tyrosine kinases. Several MET-targeting inhibitors and antagonistic antibodies have shown promising data in clinical trials of lung adenocarcinoma. Finding noninvasive diagnostic tools to estimate the status of MET is helpful in clinical practice. ¹⁸F-fluorodeoxyglucose positron emission tomography/computerized tomography (¹⁸F-FDG PET/CT) has been used routinely for the diagnosis and staging of tumors. However, the relationship between MET expression and ¹⁸F-FDG uptake has not been investigated yet. This study aimed to determine the correlation of MET expression with ¹⁸F-FDG uptake on PET-CT scan and whether or not ¹⁸F-FDG PET/CT can be used to predict the MET status of lung adenocarcinoma patients.

Patients and methods: Fifty-seven lung adenocarcinoma patients were analyzed in our study. Maximum standardized uptake value (SUV_max) was calculated in all PET/CT images. The expression levels of MET and two important glycolysis-related markers, glucose transporter 1 (GLUT1) and pyruvate kinase M2, were analyzed by immunohistochemistry of tissues. Spearman rank correlation was used to analyze the association between MET expression and SUV_max. In vitro MET knockdown in lung adenocarcinoma cells was used to examine the role of MET in tumor metabolism. The effect of MET on GLUT1 expression was investigated using Western blot assay and quantitative polymerase chain reaction.

Results: SUV_max was positively correlated with the expression levels of MET (r=0.458; P<0.001) and GLUT1 (r=0.551; P<0.001). SUV_max was significantly higher in patients with positive MET expression than in those with negative MET expression (9.92±6.62 vs 4.60±3.00; P=0.002). MET knockdown in lung adenocarcinoma cells led to a significant decrease in GLUT1 expression and ¹⁸F-FDG uptake.

Conclusion: MET could increase ¹⁸F-FDG uptake by upregulating GLUT1 expression. ¹⁸F-FDG PET/CT could be used to predict the MET status of lung adenocarcinoma patients and to supply valuable information to guide targeted therapy.

Keywords: 18F-fluorodeoxyglucose; MET; lung adenocarcinoma; maximal standardized uptake values.