68 Ga-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 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, randomised, 2×3 factorial, multicentre, 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 day 16-22, at one of three gallium-68 radioactivity ranges . 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 68 Gasatoreotide 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 68 Ga-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 3 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 68 Ga-satoreotide trizoxetan. 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 up to 50 μg were confirmed as the optimal dosing regimen for 68 Ga-satoreotide trizoxetan to be used in future phase III studies.

Patients with neuroendocrine neoplasms (NEN) have heterogeneous somatostatin receptor expression with highly differentiated lesions having higher expression. Receptor expression of the total tumor burden may be visualized by somatostatin receptor imaging, e.g. 64 Cu-DOTATATE PET/CT. Assessment of maximal lesion uptake is associated with progression-free survival (PFS), but not overall survival (OS). We hypothesized that the lesion with lowest, rather than highest, 64 Cu-DOTATATE uptake would be more prognostic and developed a semi-automatic method for evaluating this.

Overexpression of somatostatin receptors in patients with neuroendocrine neoplasms (NEN) is utilized for both diagnosis and treatment. Receptor density may reflect tumor differentiation and thus be associated with prognosis. Non-invasive visualization and quantification of somatostatin receptor density is possible by somatostatin receptor imaging (SRI) using positron emission tomography (PET). Recently, we introduced 64 Cu-DOTATATE for SRI and we hypothesized that uptake of this tracer could be associated with overall (OS) and progression-free survival (PFS). Methods We evaluated patients with NEN that had a 64 Cu-DOTATATE PET/CT SRI performed in two prospective studies. Tracer uptake was determined as the maximal standardized uptake value (SUVmax) for each patient. Kaplan-Meier analysis with log-rank was used to determine the predictive value of 64 Cu-DOTATATE SUVmax for OS and PFS. Specificity, sensitivity and accuracy was calculated for prediction of outcome at 24 months after 64 Cu-DOTATATE PET/CT. Results A total of 128 patients with NEN were included and followed for a median of 73 (1-112) months. During follow-up, 112 experienced disease progression and 69 patients died. The optimal cutoff for 64 Cu-DOTATATE SUVmax was 43.3 for prediction of PFS with a hazard ratio of 0.56 (95% CI: 0.38-0.84) for patients with SUVmax > 43.3. However, no significant cutoff was found for prediction of OS.