A Randomized, Factorial Phase II Study to Determine the Optimal Dosing Regimen for (68)Ga-Satoreotide Trizoxetan as an Imaging Agent in Patients with Gastroenteropancreatic Neuroendocrine Tumors

(68)Ga-satoreotide trizoxetan is a novel somatostatin receptor antagonist associated with high sensitivity and reproducibility in neuroendocrine tumor (NET) detection and localization. However, the optimal peptide mass and radioactivity ranges for (68)Ga-satoreotide trizoxetan have not yet been established. We therefore aimed to determine its optimal dosing regimen in patients with metastatic gastroenteropancreatic NETs in a prospective, randomized, 2 × 3 factorial, multicenter phase II study. Methods: Patients received (68)Ga-satoreotide trizoxetan at a peptide mass of 5–20 µg on day 1 of the study and of 30–45 µg on days 16–22, at 1 of 3 (68)Ga radioactivity ranges (40–80, 100–140, or 160–200 MBq). Whole-body PET/CT imaging was performed 50–70 min after each injection. The primary endpoint was the detection rate of NET lesions imaged by (68)Ga-satoreotide trizoxetan relative to contrast-enhanced CT (for each of the 6 peptide mass and radioactivity range combinations). Results: Twenty-four patients were evaluated in the per-protocol analysis. The median number of lesions detected by (68)Ga-satoreotide trizoxetan PET/CT or PET alone was at least twice as high as the number detected by contrast-enhanced CT across the 6 studied peptide mass and radioactivity range combinations. There were no differences between the 2 peptide mass ranges or between the 3 radioactivity ranges in the number of identified lesions. However, a trend toward a lower relative lesion count was noted in the liver for the 40- to 80-MBq range. No relationship was observed between the radioactivity range per patient’s body weight (MBq/kg) and the number of lesions detected by (68)Ga-satoreotide trizoxetan. The median diagnostic sensitivity of (68)Ga-satoreotide trizoxetan PET/CT, based on the number of lesions per patient, ranged from 85% to 87% across the different peptide mass and radioactivity ranges. Almost all reported adverse events were mild and self-limiting. Conclusion: A radioactivity of 100–200 MBq with a peptide mass of up to 50 µg was confirmed as the optimal dosing regimen for (68)Ga-satoreotide trizoxetan to be used in future phase III studies.