Early F-18-FDG uptake as a reliable imaging biomarker of T790M-mediated resistance but not MET amplification in non-small cell lung cancer treated with EGFR tyrosine kinase inhibitors

Animal tumor models were developed using NSCLC H1975 cells bearing the T790M mutation and H1993 cells with MET amplification. Nude mice bearing erlotinib-resistant H1975 and H1993 xenografts (four animals for each cell line and for each treatment) were subjected to F-18-FDG PET/CT scan before and immediately after treatment (50 mg/kg p.o. for 3 days) with erlotinib, WZ4002, crizotinib, or vehicle. A three-dimensional region of interest analysis was performed to determine the percent change of F-18-FDG uptake in response to treatment. At the end of the imaging studies, tumors were removed and analyzed for glycolytic and mitochondrial proteins as well as levels of cyclin D1.

Background: The two main mechanisms of resistance to EGFR tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC) are the occurrence of T790M secondary mutation in the kinase domain of EGFR and MET amplification. The aim of the present study was to test whether early changes of F-18-fluorodeoxyglucose (F-18-FDG) uptake in animal models bearing erlotinib-resistant NSCLC may have different imaging patterns of response to erlotinib depending on the molecular mechanisms underlying resistance.