A randomised, factorial phase II study to determine the optimal dosing regimen for 68 Ga-satoreotide trizoxetan as an imaging agent in patients with gastroenteropancreatic neuroendocrine tumours.

68Ga-satoreotide trizoxetan is a novel somatostatin receptor antagonist associated with high sensitivity and reproducibility in neuroendocrine tumour (NET) detection and localisation. However, the optimal peptide mass and radioactivity ranges for 68Ga-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, randomised, 2×3 factorial, multicentre, phase II study. Methods: Patients received 68Ga-satoreotide trizoxetan at a peptide mass of 5-20 µg on day 1 of the study and of 30-45 µg on day 16-22, at one of three gallium-68 radioactivity ranges (40-80, 100-140, or 160-200 MBq). Whole-body PET/CT imaging was performed 50-70 minutes after each injection. The primary endpoint was the detection rate of NET lesions imaged by 68Ga-satoreotide trizoxetan relative to contrast-enhanced CT (CECT) (for each of the six peptide mass/radioactivity range combinations). Results: Twenty-four patients were evaluated in the per-protocol analysis. The median number of lesions detected by 68Ga-satoreotide trizoxetan PET/CT or PET only was at least twice as high as the number of lesions detected by CECT across the six studied peptide mass dose/radioactivity range combinations. There were no differences between the two peptide mass ranges and between the three radioactivity ranges in the number of identified lesions. However, a trend towards a lower relative lesion count was noted in the liver for the 40-80 MBq range. No relationship was observed between the radioactivity range per patient's body weight (MBq/kg) and the number of lesions detected by 68Ga-satoreotide trizoxetan. Median diagnostic sensitivity of 68Ga-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 up to 50 μg were confirmed as the optimal dosing regimen for 68Ga-satoreotide trizoxetan to be used in future phase III studies.