| Summary: | PET imaging of neuroendocrine tumours (NET) is well established for staging and therapy follow-up. The short half-life, increasing costs, and regulatory issues significantly limit the availability of approved imaging agents, such as [<sup>68</sup>Ga]Ga-DOTA-TATE. Al[<sup>18</sup>F]F-NOTA-Octreotide provides a similar biodistribution and tumour uptake, can be produced on a large scale and may improve access to precision imaging. Here we prospectively compared the clinical utility of [<sup>68</sup>Ga]Ga-DOTA-TATE and Al[<sup>18</sup>F]F-NOTA-Octreotide in the Latin-American population. Our results showed that in patients with stage IV NETs [<sup>68</sup>Ga]Ga-DOTA-TATE presents higher physiological uptake than Al[<sup>18</sup>F]F-NOTA-Octreotide in the liver, hypophysis, salivary glands, adrenal glands (all <i>p</i> < 0.001), pancreatic uncinated process, kidneys, and small intestine (all <i>p</i> < 0.05). Nevertheless, despite the lower background uptake of Al[<sup>18</sup>F]F-NOTA-Octreotide, comparative analysis of tumour-to-liver (TLR) and tumour-to-spleen (TSR) showed no statistically significant difference for lesions in the liver, bone, lymph nodes, and other tissues. Only three discordant lesions in highly-metastases livers were detected by [<sup>68</sup>Ga]Ga-DOTA-TATE but not by Al[<sup>18</sup>F]F-NOTA-Octreotide and only one discordant lesion was detected by Al[<sup>18</sup>F]F-NOTA-Octreotide but not by [<sup>68</sup>Ga]Ga-DOTA-TATE. Non-inferiority analysis showed that Al[<sup>18</sup>F]F-NOTA-Octreotide is comparable to [<sup>68</sup>Ga]Ga-DOTA-TATE. Hence, our results demonstrate that Al[<sup>18</sup>F]F-NOTA-Octreotide provided excellent image quality, visualized NET lesions with high sensitivity and represents a highly promising, clinical alternative to [<sup>68</sup>Ga]Ga-DOTA-TATE.
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