Combination therapy inhibited tumor growth in the KRAS-mutant NSCLC xenograft and the therapeutic response could be identified by 18F-FDG PET imaging. When tumor volumes reached approximately 200–300 mm3, mice were randomly assigned to one of four groups (5 mice per group) and treated via oral gavage twice per day for six days acutely: control (vehicle alone), selumetinib (25 mg/kg), CB839 (200 mg/kg), selumetinib (25 mg/kg)+CB839 (200 mg/kg). (A)The tumor volume curve before and after treatment. (B) Tumor volumes represented as fold change pre- and post-treatment. (C) Representative micro-PET images of mice bearing A549 xenografts with18F-FDG pre- and post-treatment. Tumors are indicated by arrows. (D) Quantification of 18F-FDG uptake represented as fold change of SUVmax pre- and post-treatment. Data were presented as mean±SD(n = 5). A p-value <0.05 was considered statistically significant (*p<0.05, **p<0.01,***p<0.001; *in black: compared with control group, * in red: compared with SE group, * in green: compared with CB group).