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

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://ichgcp.net/clinical-trials-registry/NCT03220217.

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

Conflict of interest statement

CGM has acted as a consultant for Ipsen, CytoSite Bio and Alacrita, and is a managing partner at the Bracken Group. HG serves on the advisory board of Ipsen. IV has acted as a consultant for Ipsen and Advanced Accelerator Applications. AK has served on the advisory board of Ipsen. PT is an employee at Keosys. TR is a managing partner at Partner 4 Health, and has acted as a consultant for Ipsen. SM is an employee at Ipsen Bioscience (Cambridge, MA, USA). No other potential conflict of interest relevant to this article was reported.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
Study design. Abbreviations: CT, computed tomography; GEP, gastroenteropancreatic; NET, neuroendocrine tumour; PET, positron emission tomography; R, randomised
Fig. 2
Fig. 2
Read design. Abbreviations: CT, computed tomography; PET, positron emission tomography; R, reader
Fig. 3
Fig. 3
Two 68Ga-satoreotide trizoxetan PET/CT fused images with maximum intensity projection of the same patient acquired at two different timepoints separated by 2–3 weeks. In the top panel, the patient had received 68Ga-satoreotide trizoxetan at 16 µg/165 MBq. In the lower panel, the patient had received 68Ga-satoreotide trizoxetan at 32 µg/72 MBq. Abbreviations: CT, computed tomography; PET, positron emission tomography

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