18 F-AlF-NOTA-Octreotide Outperforms 68 Ga-DOTATATE/NOC PET in Neuroendocrine Tumor Patients: Results from a Prospective, Multicenter Study.

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.)