¹⁸F-AlF-NOTA-octreotide outperforms⁶⁸Ga-DOTA-TATE/-NOC PET in neuroendocrine tumor patients: results from a prospective, multicenter study

¹⁸F-labeled somatostatin analogs (SSAs) could represent a valid alternative to the current gold standard, ⁶⁸Ga-labeled SSAs, for somatostatin receptor imaging in patients with neuroendocrine tumors (NETs), given their logistic advantages. Recently, ¹⁸F-AlF-NOTA-octreotide (¹⁸F-AlF-OC) has emerged as a promising candidate, but a thorough comparison with ⁶⁸Ga-DOTA-SSA in large patient groups is needed. This prospective, multicenter trial aims to demonstrate noninferiority of ¹⁸F-AlF-OC compared with ⁶⁸Ga-DOTA-SSA PET in NET patients (ClinicalTrials.gov, NCT04552847). Methods: Seventy-five patients with histologically confirmed NET and routine clinical ⁶⁸Ga-DOTATATE (n = 56) or ⁶⁸Ga-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 ¹⁸F-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 ¹⁸F-AlF-OC and ⁶⁸Ga-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 ⁶⁸Ga-DOTATATE/NOC and 4,278 with ¹⁸F-AlF-OC. The mean DR with ¹⁸F-AlF-OC was significantly higher than with ⁶⁸Ga-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 ⁶⁸Ga-DOTATATE and ⁶⁸Ga-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 ¹⁸F-AlF-OC than with ⁶⁸Ga-DOTATATE/NOC (31.7 ± 36.5 vs. 25.1 ± 32.7; P = 0.001). Conclusion:¹⁸F-AlF-OC is noninferior and even superior to ⁶⁸Ga-DOTATATE/NOC PET in NET patients. This validates ¹⁸F-AlF-OC as an option for clinical practice somatostatin receptor PET.