Research ArticleCancer

A PET imaging approach for determining EGFR mutation status for improved lung cancer patient management

See allHide authors and affiliations

Science Translational Medicine  07 Mar 2018:
Vol. 10, Issue 431, eaan8840
DOI: 10.1126/scitranslmed.aan8840

You are currently viewing the abstract.

View Full Text

Log in to view the full text

Log in through your institution

Log in through your institution

Tracing tumor treatment response

Tyrosine kinase inhibitors (TKIs) are a therapy for patients with non–small cell lung cancer (NSCLC) who have activating mutations in epidermal growth factor receptor (EGFR). To noninvasively detect tumor mutation status, Sun et al. designed a radiolabeled tracer for use with positron emission tomography and computed tomography imaging methods. The tracer identified tumors with activating mutant EGFR in rodent models of NSCLC and in patients with NSCLC. Patients with mutant EGFR had longer progression-free survival and responded to TKI therapy at a higher rate compared to patients with wild-type EGFR. This tracer could help identify patients with EGFR-TKI sensitivity and could be useful for monitoring response to treatment.


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.

View Full Text