18 F-AlF-NOTA-octreotide outperforms 68 Ga-DOTA-TATE/-NOC PET in neuroendocrine tumor patients: results from a prospective, multicenter study.

Fluorine-18-labeled somatostatin analogs (SSAs) could represent a valid alternative to the current gold standard gallium-68-labeled SSAs for somatostatin receptor (SSTR) imaging in patients with neuroendocrine tumors (NETs), given their logistical 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 non-inferiority 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 a routine clinical 68 Ga-DOTATATE ( n = 56) or 68 Ga-DOTANOC ( n = 19) PET, performed within a 3-month interval of the study scan (median: 7 days; range: -30 to +32 days), were included. Patients underwent a whole-body PET, two hours after IV injection of 4 MBq/kg 18 F-AlF-OC. A randomized, blinded consensus read was performed by two experienced readers to count tumor lesions. Following unblinding, the detection ratio (DR) was determined for each scan, i.e. the fraction of lesions detected on a scan compared to the union of lesions of both scans. The differential detection ratio (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 (TBRs) in concordant lesions. Results: In total, 4709 different tumor lesions were detected, 3454 with 68 Ga-DOTATATE/NOC and 4278 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% confidence interval (95% CI: 9.6%-22.0%) higher than -15%, the pre-specified boundary for non-inferiority. The mean DDR 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: -17.8-12.2)). No significant differences in mean SUV max were observed ( P = 0.067), but mean TBR 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 non-inferior and even superior compared with 68 Ga-DOTATATE/NOC PET in NET patients. This validates 18 F-AlF-OC as an option for clinical practice SSTR PET.