PurposesTo explore the clinical feasibility and efficacy of a deep inspiration breath-hold (BH) PET/CT using [18F]AlF-NOTA-LM3 on upper abdominal lesions in patients with neuroendocrine tumors (NETs).MethodsTwenty-three patients underwent a free-breath (FB) whole-body PET/CT, including a 10 min/bed scan for the upper abdomen with a vital signal monitoring for respiratory gating (RG) followed by a 20-second BH PET/CT covering the same axial range. For the upper abdomen bed, the following PET series was reconstructed: a 2-min FB PET; RG PET (6 bins); a 20-second and 15-second BH PET (BH_15 and BH_20). Semi-quantitative analysis was performed to compare liver SUVmean, lesion SUVmax, MTV, its percentage difference and target-to-background ratio (TBR) between both BH PET and RG PET images. Subgroup analysis considered lesion location, MTV and SUVmax. A 5-point Likert scale was used to perform visual analysis and any missed or additional lesions were identified compared with RG PET.ResultsQuantitative analysis on overall lesions (n = 78) revealed higher SUVmax and TBR, and smaller MTV for both BH PET compared to FB and RG PET, with lesion location-specific variations. Neither significant difference was observed in all metrics between RG and FB PET in larger lesions, nor in MTV in lower-uptake lesions. However, both BH PET significantly enhanced these measurements. In the visual analysis, both BH PET showed noninferior performance to RG PET, and were evaluated clinically acceptable. Additional and missed lesions were observed in FB and both BH PET compared with RG PET, but didn’t alter the clinical management. The BH_15 PET showed comparable performance to BH_20 PET in any comparison.ConclusionThe BH PET/CT using [18F]AlF-NOTA-LM3 is effective in detecting upper abdominal lesions, offering more accurate quantitative measurements. Using a novel PET/CT scanner, a 15-second BH PET can provide comparable and superior performance to RG PET, indicating potential feasibility in clinical routines.