바로가기  >

Abstract

Tumor heterogeneity and changes in epidermal growth factor receptor (EGFR) mutation status over time challenge the design of effective EGFR tyrosine kinase inhibitor (TKI) treatment strategies for non-small cell lung cancer (NSCLC). Therefore, there is an urgent need to develop techniques for comprehensive tumor EGFR profiling in real time, particularly in lung cancer precision medicine trials. We report a positron emission tomography (PET) tracer, N-(3-chloro-4-fluorophenyl)-7-(2-(2-(2-(2-18F-fluoroethoxy) ethoxy) ethoxy) ethoxy)-6-methoxyquinazolin-4-amine (18F-MPG), with high specificity to activating EGFR mutant kinase. We evaluate the feasibility of using 18F-MPG PET for noninvasive imaging and quantification of EGFR-activating mutation status in preclinical models of NSCLC and in patients with primary and metastatic NSCLC tumors. 18F-MPG PET in NSCLC animal models showed a significant correlation (R2 = 0.9050) between 18F-MPG uptake and activating EGFR mutation status. In clinical studies with NSCLC patients (n = 75), the concordance between the detection of EGFR activation by 18F-MPG PET/computed tomography (CT) and tissue biopsy reached 84.29%. There was a greater response to EGFR-TKIs (81.58% versus 6.06%) and longer median progression-free survival (348 days versus 183 days) in NSCLC patients when 18F-MPG PET/CT SUVmax (maximum standard uptake value) was ≥2.23 versus <2.23. Our study demonstrates that 18F-MPG PET/CT is a powerful method for precise quantification of EGFR-activating mutation status in NSCLC patients, and it is a promising strategy for noninvasively identifying patients sensitive to EGFR-TKIs and for monitoring the efficacy of EGFR-TKI therapy.

Author information

Sun X1,2,3, Xiao Z1, Chen G4, Han Z1, Liu Y1, Zhang C1, Sun Y2, Song Y1, Wang K1,2, Fang F2, Wang X1, Lin Y1, Xu L5, Shao L5, Li J6, Cheng Z7, Gambhir SS7, Shen B8,2.

1 Molecular Imaging Research Center, Harbin Medical University (MIRC), Harbin, Heilongjiang 150028, China.
2 TOF-PET/CT/MR Center, The Fourth Hospital of Harbin Medical University, Harbin, Heilongjiang 150028, China.
3 Molecular Imaging Program at Stanford (MIPS), Department of Radiology, Stanford University School of Medicine, Stanford, CA 94305, USA.
4 Department of Respiratory Medical Oncology, The Tumor Hospital Affiliated Harbin Medical University, Harbin, Heilongjiang 150049, China.
5 School of Pharmacy, Fudan University, Shanghai 201203, China.
6 College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150081, China.
7 Molecular Imaging Program at Stanford (MIPS), Department of Radiology, Stanford University School of Medicine, Stanford, CA 94305, USA. shenbz@ems.hrbmu.edu.cn sgambhir@stanford.edu zcheng@stanford.edu.
8 Molecular Imaging Research Center, Harbin Medical University (MIRC), Harbin, Heilongjiang 150028, China. shenbz@ems.hrbmu.edu.cn sgambhir@stanford.edu zcheng@stanford.edu.