1. A randomised, factorial phase II study to determine the optimal dosing regimen for 68Ga-satoreotide trizoxetan as an imaging agent in patients with gastroenteropancreatic neuroendocrine tumours
- Author
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Virgolini, Irene, Bahri, Shadfar, Kjaer, Andreas, Grønbæk, Henning, Iversen, Peter, Carlsen, Esben A, Loft, Mathias, Knigge, Ulrich, Maffey-Steffan, Johanna, Powell, Christine, Miller, Colin G, Rohban, Thomas, McEwan, Sandy, and Czernin, Johannes
- Subjects
Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Clinical Research ,Cancer ,Clinical Trials and Supportive Activities ,Biomedical Imaging ,4.1 Discovery and preclinical testing of markers and technologies ,Detection ,screening and diagnosis ,4.2 Evaluation of markers and technologies ,Gallium Radioisotopes ,Humans ,Intestinal Neoplasms ,Neuroendocrine Tumors ,Octreotide ,Organometallic Compounds ,Pancreatic Neoplasms ,Positron Emission Tomography Computed Tomography ,Prospective Studies ,Radiopharmaceuticals ,Reproducibility of Results ,Stomach Neoplasms ,Ga-68-satoreotide trizoxetan ,neuroendocrine tumors ,somatostatin receptor antagonist ,diagnostic imaging ,optimal dose ,68Ga-satoreotide trizoxetan ,Nuclear Medicine & Medical Imaging ,Clinical sciences - Abstract
68Ga-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 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, randomized, 2 × 3 factorial, multicenter 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 days 16-22, at 1 of 3 68Ga 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 68Ga-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 68Ga-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 68Ga-satoreotide trizoxetan. The 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 of up to 50 µg was confirmed as the optimal dosing regimen for 68Ga-satoreotide trizoxetan to be used in future phase III studies.
- Published
- 2022