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Background:The detection of solitary pulmonary nodules (SPNs) that may potentially develop into a malignant lesion is essential for early clinical interventions.However,grading classification based on computed tomography (CT) imaging results remains a significant challenge.The 2-[18F]-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography (PET)/CT imaging produces both false-positive and false-negative findings for the diagnosis of SPNs.In this study,we compared 18F-FDG and 3-deoxy-3-[18F]-fluorothymidine (18F-FLT) in lung cancer PET/CT imaging.Methods:The binding ratios of the two tracers to A549 lung cancer cells were calculated.The mouse lung cancer model was established (n =12),and micro-PET/CT analysis using the two tracers was performed.Images using the two tracers were collected from 55 lung cancer patients with SPNs.The correlation among the cell-tracer binding ratios,standardized uptake values (SUVs),and Ki-67 proliferation marker expression were investigated.Results:The cell-tracer binding ratio for the A549 cells using the 18F-FDG was greater than the ratio using 18F-FLT (P ＜ 0.05).The Ki-67 expression showed a significant positive correlation with the 18F-FLT binding ratio (r =0.824,P ＜ 0.01).The tumor-to-nontumor uptake ratio of 18F-FDG imaging in xenografts was higher than that of 18F-FLT imaging.The diagnostic sensitivity,specificity,and the accuracy of 18F-FDG for lung cancer were 89％,67％,and 73％,respectively.Moreover,the diagnostic sensitivity,specificity,and the accuracy of 18F-FLT for lung cancer were 71％,79％,and 76％,respectively.There was an obvious positive correlation between the lung cancer Ki-67 expression and the mean maximum SUV of 18F-FDG and 18F-FLT (r =0.658,P ＜ 0.05 and r =0.724,P ＜ 0.01,respectively).Conclusions:The 18F-FDG uptake ratio is higher than that of 18F-FLT in A549 cells at the cellular level.18F-FLT imaging might be superior for the quantitative diagnosis of lung tumor tissue and could distinguish lung cancer nodules from other SPNs.