Purpose <p>The EANM/SNMMI guidelines recommend an uptake time of 60&#xa0;min for 2-[¹⁸F]fluoro-2-deoxy-D-glucose ([¹⁸F]FDG) in oncology imaging, with an acceptable range of 55 to 75&#xa0;min. Over time, positron emission tomography (PET) technology has advanced significantly in terms of signal collection efficiency. This study aims to explore the feasibility of PET acquisition after a 40-minute uptake period following [¹⁸F]FDG administration in patients with tumours.</p> Methods <p>Forty-three oncological patients who underwent 60-min total-body dynamic [¹⁸F]FDG PET scan were retrospectively included as the exploration cohort. The raw data was reconstructed into 55 image frames to calculate and compare the lesion-to-background ratios (LBRs) of different image frames (G_D57−60 served as the reference). The data from 40 to 52&#xa0;min and 57–60&#xa0;min were then reconstructed into static PET images (G_{40 − 43}, G_{43 − 46}, G_{46 − 49}, G_{49 − 52}, and G_{57 − 60}). The differences in image quality (subjective image score, standardized uptake value [SUV], signal-to-noise ratio [SNR], and LBRs) and lesion-detection rate (histopathology served as reference) among groups were evaluated. In the validation cohort, 46 oncological patients who underwent a 20-min total-body PET/CT scan at 40&#xa0;min after [¹⁸F]FDG injection were prospectively enrolled. The raw data were reconstructed using the same protocols with dynamic scan and briefly called: G_{40 − 43’}, G_{43 − 46’}, G_{46 − 49’}, G_{49 − 52’}, and G_{57 − 60’}, and the image quality and lesion detection rate among groups were assessed.</p> Results <p>The activity curves reveal that the average LBRs gradually increased with time, with no significant difference between G_D45−48 and G_D57−60 (all <i>p</i> ≥ 0.27). The static PET image quality in both cohorts was as good as the 57-min uptake imaging. In the exploration cohort, the SNRs of G_{57 − 60} were not better than the other groups. For all lesions, SUV_max, lesion-to-liver ratio (LLR), lesion-to-muscle ratio (LMR), and lesion-to-normal tissue ratio (LNR) showed no statistically significant differences between G_{49 − 52} and G_{57 − 60} (all <i>p</i> ≥ 0.06), with the exception of lesion-to-blood pool ratio (LBPR) (<i>p</i> &lt; 0.05). The lesion-detection rate was 85.7% (48/56; 95% CI: 0.74–0.94) in all groups. In the validation cohort, G_{40 − 43’} and G_{57 − 60’} shared comparable background SNRs and the same lesion detection rate (94.0%, 63/67; 95% CI: 0.85–0.98).</p> Conclusion <p>Reducing the uptake time from 60&#xa0;min to 40&#xa0;min after [¹⁸F]FDG injection in oncology patients can still yield PET images with sufficient quality and lesion detectability to meet clinical requirements in total body PET/CT. Shortening the uptake time raised the efficiency of the uptake room, increased patient throughput, and enhanced patient comfort, without changing the scan protocol or compromising imaging quality.</p>