PurposeFor the first time, three currently available 360° CZT-SPECT/CT cameras were compared under clinical conditions using phantom-based measurements.MethodsA 99mTc- and a 177Lu-customized NEMA IEC body phantom were imaged with three different cameras, StarGuide (GE Healthcare), VERITON-CT versions 200 (V200) and 400 (V400) (Spectrum Dynamics Medical) under the same clinical conditions. Energy resolution and volumetric sensitivity were evaluated from energy spectra. Vendors provided the best reconstruction parameters dedicated to visualization and/or quantification, based on their respective software developments. For both 99mTc- and 177Lu-phantoms, noise level, quantification accuracy, and recovery coefficient (RC) were performed with 3DSlicer. Image quality metrics from an approach called “task-based” were computed with iQMetrix-CT on 99mTc visual reconstructions to assess, through spatial frequencies, noise texture in the background (NPS) and contrast restitution of a hot insert (TTF). Spatial resolution indices were calculated from frequencies corresponding to TTF10% and TTF50%.ResultsDespite the higher sensitivity of VERITON cameras and the enhanced energy resolution of the V400 (3.2% at 140 keV, 5.2% at 113 keV, and 3.6% at 208 keV), StarGuide presents comparable image quality. This highlights the need to differentiate sensitivity from count quality, which is influenced by hardware design (collimator, detector block) and conditions image quality as well as the reconstruction process (algorithms, scatter correction, noise regulation). For 99mTc imaging, the quantitative image optimization approach based on RCmean for StarGuide versus RCmax for V200 and V400 systems (RCmean/RCmax: 0.9/1.8; 0.5/0.9; 0.5/0.9 respectively—Ø37 mm). SRTB10/50 showed nearly equivalent spatial resolution performances across the different reconstructed images. For 177Lu imaging, the 113 keV imaging of the V200 and V400 systems demonstrated strong performances in both image quality and quantification, while StarGuide and V400 systems offer even better potential due to their ability to exploit signals from both the 113 and 208 keV peaks. 177Lu quantification was optimized according to RCmax for all cameras and reconstructions (1.07 ± 0.09—Ø37 mm).ConclusionsThe three cameras have equivalent potential for 99mTc imaging, while StarGuide and V400 have demonstrated higher potential for 177Lu. Dedicated visual or quantitative reconstructions offer better specific performances compared to the unified visual/quantitative reconstruction. The task-based approach appears to be promising for in-depth comparison of images in the context of system characterization/comparison and protocol optimization.