ObjectiveThis study aims to assess the impact of various regions of interest (ROIs) and volumes of interest (VOIs) delineations on the reproducibility of liver signal-to-noise-ratio (SNRliver) measurements, as well as to find the most reproducible way to estimate it in gallium-68 positron emission tomography (68Ga-PET) imaging. We also investigated the SNRliver-weight relationship for these ROIs and VOIs delineations.MethodsA cohort of 40 patients (40 males; mean weight: 76.5 kg [58–115 kg]) with prostate cancer were included.68Ga-PET/CT imaging (mean injected activity: 91.4 MBq [51.2 MBq to 134.1 MBq] was performed on a 5-ring bismuth germanium oxide-based Discovery IQ PET/CT using ordered subset expectation maximization image reconstruction algorithm. Afterward, circular ROIs and spherical VOIs with two different diameters of 30 and 40 mm were drawn on the right lobe of the livers. The performance of the various defined regions was evaluated by the average standardized uptake value (SUVmean), standard deviation (SD) of the SUV (SUVSD), SNRliver, and SD of the SNRlivermetrics.ResultsThere were no significant differences in SUVmeanamong the various ROIs and VOIs (p> 0.05). On the other hand, the lower SUVSDwas obtained by spherical VOI with diameter of 30 mm. The largest SNRliverwas obtained by ROI (30 mm). The SD of SNRliverwith ROI (30 mm) was also the largest, while the lowest SD of SNRliverwas observed for VOI (40 mm). There is a higher correlation coefficient between the patient-dependent parameter of weight and the image quality parameter of SNRliver for both VOI (30 mm) and VOI (40 mm) compared to the ROIs.ConclusionOur results indicate that SNRlivermeasurements are affected by the size and shape of the respective ROIs and VOIs. The spherical VOI with a 40 mm diameter leads to more stable and reproducible SNR measurement in the liver.