A novel read methodology to evaluate the optimal dose of 68Ga-satoreotide trizoxetan as a PET imaging agent in patients with gastroenteropancreatic neuroendocrine tumours: a phase II clinical trial

Colin G Miller; Henning Grønbæk; Irene Virgolini; Andreas Kjaer; Pierre Terve; Shadfar Bahri; Peter Iversen; Hanna Svirydenka; Thomas Rohban; Sandy McEwan

doi:10.1186/s13550-021-00819-1

A novel read methodology to evaluate the optimal dose of ⁶⁸Ga-satoreotide trizoxetan as a PET imaging agent in patients with gastroenteropancreatic neuroendocrine tumours: a phase II clinical trial

EJNMMI Res. 2021 Sep 6;11(1):84. doi: 10.1186/s13550-021-00819-1.

Authors

Affiliations

¹ The Bracken Group for Ipsen Bioscience, 12 Penns Trail, Newtown, PA, 18940, USA. cmiller@thebrackengroup.com.
² Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.
³ Department of Nuclear Medicine, University of Innsbruck, Innsbruck, Austria.
⁴ Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Department of Biomedical Sciences, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
⁵ Keosys, Nantes, France.
⁶ Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.
⁷ Department of Nuclear Medicine and PET Center, Aarhus University Hospital, Aarhus, Denmark.
⁸ Partner 4 Health for Ipsen Bioscience, Paris, France.
⁹ Ipsen Bioscience, Cambridge, MA, USA.

Abstract

Background: ⁶⁸Ga-satoreotide trizoxetan is a novel somatostatin receptor antagonist exhibiting higher tumour-to-background ratios and sensitivity compared to ⁶⁸Ga-DOTATOC. This randomised, 2 × 3 factorial, phase II study aimed to confirm the optimal peptide mass and radioactivity ranges for ⁶⁸Ga-satoreotide trizoxetan, using binary visual reading. To that end, 24 patients with metastatic gastroenteropancreatic neuroendocrine tumours received 5-20 µg of ⁶⁸Ga-satoreotide trizoxetan on day 1 of the study and 30-45 µg on day 16-22, with one of three gallium-68 radioactivity ranges (40-80, 100-140, or 160-200 MBq) per visit. Two ⁶⁸Ga-satoreotide trizoxetan PET/CT scans were acquired from each patient post-injection, and were scored by experienced independent blinded readers using a binary system (0 for non-optimal image quality and 1 for optimal image quality). For each patient pair of ⁶⁸Ga-satoreotide trizoxetan scans, one or both images could score 1.

Results: Total image quality score for ⁶⁸Ga-satoreotide trizoxetan PET scans was lower in the 40-80 MBq radioactivity range (56.3%) compared to 100-140 MBq (90.6%) and 160-200 MBq (81.3%). Both qualitative and semi-quantitative analysis showed that peptide mass (5-20 or 30-45 µg) did not influence ⁶⁸Ga-satoreotide trizoxetan imaging. There was only one reading where readers diverged on scoring; one reader preferred one image because of higher lesion conspicuity, and the other reader preferred the alternative image because of the ability to identify more lesions.

Conclusions: Binary visual reading, which was associated with a low inter-reader variability, has further supported that the optimal administered radioactivity of ⁶⁸Ga-satoreotide trizoxetan was 100-200 MBq with a peptide mass up to 50 µg. Trial registration ClinicalTrials.gov, NCT03220217. Registered 18 July 2017, https://clinicaltrials.gov/ct2/show/NCT03220217.

Keywords: 68Ga-satoreotide trizoxetan; Binary visual reading; Diagnostic imaging; Neuroendocrine tumours; Somatostatin receptor antagonist.

Associated data

ClinicalTrials.gov/NCT03220217