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Molecular imaging of the somatostatin receptor plays a key role in the clinical management of neuroendocrine tumors. PET imaging with somatostatin analogs (SSAs) labeled with 68 Ga or 64 Cu is currently the gold standard in clinical practice. However, widespread implementation of 68 Ga imaging is often hampered by practical and economic issues related to 68 Ge/ 68 Ga generators. 18 F offers several advantages to tackle these issues. Recent developments in radiochemistry have allowed a shift from 68 Ga toward 18 F labeling, leading to promising clinical translations of 18 F-labeled SSAs, such as Gluc-Lys-[ 18 F]FP-TOCA, [ 18 F]F-FET-βAG-TOCA, [ 18 F]AlF-NOTA-octreotide, [ 18 F]SiTATE, and [ 18 F]AlF-NOTA-JR11. This review gives an update of currently available clinical data regarding 18 F-labeled SSA tracers and provides justification for the clinical application of this class of tracers., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

18 F-labeled somatostatin analogs (SSAs) could represent a valid alternative to the current gold standard, 68 Ga-labeled SSAs, for somatostatin receptor imaging in patients with neuroendocrine tumors (NETs), given their logistic advantages. Recently, 18 F-AlF-NOTA-octreotide ( 18 F-AlF-OC) has emerged as a promising candidate, but a thorough comparison with 68 Ga-DOTA-SSA in large patient groups is needed. This prospective, multicenter trial aims to demonstrate noninferiority of 18 F-AlF-OC compared with 68 Ga-DOTA-SSA PET in NET patients (ClinicalTrials.gov, NCT04552847). Methods: Seventy-five patients with histologically confirmed NET and routine clinical 68 Ga-DOTATATE ( n = 56) or 68 Ga-DOTANOC ( n = 19) PET, performed within a 3-mo interval of the study scan (median, 7 d; range, -30 to +32 d), were included. Patients underwent a whole-body PET 2 h after intravenous injection of 4 MBq/kg of 18 F-AlF-OC. A randomized, masked consensus read was performed by 2 experienced readers to count tumor lesions. After unmasking, the detection ratio (DR) was determined for each scan, that is, the fraction of lesions detected on a scan compared with the union of lesions of both scans. The differential DR (DDR; difference in DR between 18 F-AlF-OC and 68 Ga-DOTATATE/NOC) per patient was calculated. Tracer uptake was evaluated by comparing SUV max and tumor-to-background ratios in concordant lesions. Results: In total, 4,709 different tumor lesions were detected: 3,454 with 68 Ga-DOTATATE/NOC and 4,278 with 18 F-AlF-OC. The mean DR with 18 F-AlF-OC was significantly higher than with 68 Ga-DOTATATE/NOC (91.1% vs. 75.3%; P < 10 -5 ). The resulting mean DDR was 15.8%, with a lower margin of the 95% CI (95% CI, 9.6%-22.0%) higher than -15%, which is the prespecified boundary for noninferiority. The mean DDRs for the 68 Ga-DOTATATE and 68 Ga-DOTANOC subgroups were 11.8% (95% CI, 4.3-19.3) and 27.5% (95% CI, 17.8-37.1), respectively. The mean DDR for most organs was higher than zero, except for bone lesions (mean DDR, -2.8%; 95% CI, -17.8 to 12.2). No significant differences in mean SUV max were observed ( P = 0.067), but mean tumor-to-background ratio was significantly higher with 18 F-AlF-OC than with 68 Ga-DOTATATE/NOC (31.7 ± 36.5 vs. 25.1 ± 32.7; P = 0.001). Conclusion: 18 F-AlF-OC is noninferior and even superior to 68 Ga-DOTATATE/NOC PET in NET patients. This validates 18 F-AlF-OC as an option for clinical practice somatostatin receptor PET., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)