Brain metastases are frequent complications for lung cancer patients. However, changes in the brain of lung cancer patients have received little attention. We aimed to explore whether alterations in brain glucose uptake and brain texture occur in non‐small cell lung cancer (NSCLC) patients and to investigate associations between brain alterations and NSCLC via the uEXPLORER positron emission tomography/computed tomography (PET/CT) system.

In total, 105 participants were enrolled, including 55 healthy controls and 50 NSCLC patients. Images were acquired using the PET/CT system. Standardized uptake values normalized by lean body mass were calculated as indicators of glucose uptake. Correlation analysis was conducted between aberrant brain glucose uptake, glucose uptake of cancer lesions, and concentrations of serum lung cancer markers. Radiomics was used to investigate whether features extracted from regions with altered brain glucose uptake could serve as biomarkers of lung cancer progression.

Compared with healthy controls, NSCLC patients showed decreased standardized uptake values normalized by lean body mass in the left insula, medial frontal gyrus, and anterior cingulate. Correlation analysis demonstrated that glucose uptake of the anterior cingulate was negatively correlated with serum lung cancer marker concentrations. Radiomic features on PET/CT images of the above brain regions could classify NSCLC patients and healthy controls with an accuracy of 79%.

NSCLC patients exhibited altered brain glucose uptake and changes in brain textures. These alterations may reflect alterations in behavioral domains in NSCLC and may be related to altered lung‐brain interactions and potential brain metastasis of NSCLC.