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Purpose: This study aimed to evaluate the clinical feasibility of early 30-minute dynamic 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG) positron emission tomography (PET) scanning protocol for patients with lung lesions in comparison to the standard 65-minute dynamic FDG-PET scanning as a reference. Methods: Dynamic 18F-FDG PET images of 146 patients with 181 lung lesions (including 146 lesions confirmed by histology) were analyzed in this prospective study. Dynamic images were reconstructed into 28 frames with a specific temporal division protocol for the scan data acquired 65 min post-injection. Ki images and quantitative parameters Ki based on two different acquisition durations [the first 30 min (Ki-30 min) and 65 min (Ki-65 min)] were obtained by applying the irreversible two-tissue compartment model using in-house Matlab software. The two acquisition durations were compared for Ki image quality (including visual score analysis and number of lesions detected) and Ki value (including accuracy of Ki, the value of differential diagnosis of lung lesions and prediction of PD-L1 status) by Wilcoxon's rank sum test, Spearman's rank correlation analysis, receiver operating characteristic (ROC) curve, and the DeLong test. The significant testing level (alpha) was set to 0.05. Results: The quality of the Ki-30 min images was not significantly different from the Ki-65 min images based on visual score analysis (P > 0.05). In terms of Ki value, among 181 lesions, Ki-65 min was statistically higher than Ki-30 min (0.027 ± 0.017 ml/g/min vs. 0.026 ± 0.018 ml/g/min, P < 0.05), while a very high correlation was obtained between Ki-65 min and Ki-30 min (r = 0.977, P < 0.05). In the differential diagnosis of lung lesions, ROC analysis was performed on 146 histologically confirmed lesions, the area under the curve (AUC) of Ki-65 min, Ki-30 min, and SUVmax was 0.816, 0.816, and 0.709, respectively. According to the Delong test, no significant differences in the diagnostic accuracies were found between Ki-65 min and Ki-30 min (P > 0.05), while the diagnostic accuracies of Ki-65 min and Ki-30 min were both significantly higher than that of SUVmax (P < 0.05). In 73 (NSCLC) lesions with definite PD-L1 expression results, the Ki-65 min, Ki-30 min, and SUVmax in PD-L1 positivity were significantly higher than that in PD-L1 negativity (P < 0.05). And no significant differences in predicting PD-L1 positivity were found among Ki-65 min, Ki-30 min, and SUVmax (AUC = 0.704, 0.695, and 0.737, respectively, P > 0.05), according to the results of ROC analysis and Delong test. Conclusions: This study indicates that an early 30-minute dynamic FDG-PET acquisition appears to be sufficient to provide quantitative images with good-quality and accurate Ki values for the assessment of lung lesions and prediction of PD-L1 expression. Protocols with a shortened early 30-minute acquisition time may be considered for patients who have difficulty with prolonged acquisitions to improve the efficiency of clinical acquisitions. [ABSTRACT FROM AUTHOR]