Somatostatin Receptor Imaging with [¹⁸F]FET-βAG-TOCA PET/CT and [⁶⁸Ga]Ga-DOTA-Peptide PET/CT in Patients with Neuroendocrine Tumors: A Prospective, Phase 2 Comparative Study

There is a clinical need for ¹⁸F-labeled somatostatin analogs for the imaging of neuroendocrine tumors (NET), given the limitations of using [⁶⁸Ga]Ga-DOTA-peptides, particularly with regard to widespread accessibility. We have shown that [¹⁸F]fluoroethyl-triazole-[Tyr³]-octreotate ([¹⁸F]FET-βAG-TOCA) has favorable dosimetry and biodistribution. As a step toward clinical implementation, we conducted a prospective, noninferiority study of [¹⁸F]FET-βAG-TOCA PET/CT compared with [⁶⁸Ga]Ga-DOTA- peptide PET/CT in patients with NET. Methods: Forty-five patients with histologically confirmed NET, grades 1 and 2, underwent PET/CT imaging with both [¹⁸F]FET-βAG-TOCA and [⁶⁸Ga]Ga-peptide performed within a 6-mo window (median, 77 d; range, 6–180 d). Whole-body PET/CT was conducted 50 min after injection of 165 MBq of [¹⁸F]FET-βAG-TOCA. Tracer uptake was evaluated by comparing SUVmax and tumor-to-background ratios at both lesion and regional levels by 2 unblinded, experienced readers. A randomized, blinded reading of both scans was also then undertaken by 3 experienced readers, and consensus was assessed at a regional level. The ability of both tracers to visualize liver metastases was also assessed. Results: A total of 285 lesions were detected on both imaging modalities. An additional 13 tumor deposits were seen in 8 patients on [¹⁸F]FET-βAG-TOCA PET/CT, and [⁶⁸Ga]Ga-DOTA-peptide PET/CT detected an additional 7 lesions in 5 patients. Excellent correlation in SUVmax was observed between both tracers (r = 0.91; P < 0.001). No difference was observed between median SUVmax across regions, except in the liver, where the median tumor-to-background ratio of [¹⁸F]FET-βAG-TOCA was significantly lower than that of [⁶⁸Ga]Ga-DOTA-peptide (2.5 ± 1.9 vs. 3.5 ± 2.3; P < 0.001). Conclusion: [¹⁸F]FET-βAG-TOCA was not inferior to [⁶⁸Ga]Ga-DOTA-peptide in visualizing NET and may be considered in routine clinical practice given the longer half-life and availability of the cyclotron-produced fluorine radioisotope.