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

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

Galanin potentiates supramaximal caerulein-stimulated pancreatic amylase secretion via its action on somatostatin secretion

Galanin inhibits pancreatic amylase secretion from mouse lobules induced by physiological concentrations of caerulein via an insulin-dependent mechanism. We aimed to determine the effect and elucidate the mechanism of action of exogenous galanin on pancreatic amylase secretion induced by supramaximal concentrations of caerulein. Amylase secretion from isolated murine pancreatic lobules was measured. Lobules were coincubated with galanin (10−12–10−7 M) and caerulein (10−7 M). Lobules were preincubated with atropine (10−5 M), tetrodotoxin (10−5 M), diazoxide (10−7 M), or the galanin antagonist galantide (10−12–10−7 M) for 30 min followed by incubation with caerulein alone, or combined with galanin (10−12 M). Lobules were also coincubated with combinations of galanin (10−12 M), caerulein, octreotide (10−12–10−7 M) or cyclo-(7-aminoheptanoyl-Phe-D-Trp-Lys-Thr[BZL]), a somatostatin receptor antagonist (10−9 M). Amylase secretion was expressed as percent of total lobular amylase. Caerulein stimulated amylase secretion to 124% of control. Diazoxide pretreatment abolished the caerulein-stimulated amylase secretion, whereas atropine or tetrodotoxin caused a partial inhibition. Galanin (10−12–10−7 M) potentiated caerulein-stimulated amylase secretion to 160% of control. Preincubation with a combination of atropine and diazoxide abolished the potentiating effect of galanin, indicating muscarinic receptor and insulin mediation. Preincubation with galantide abolished the galanin effect, implying galanin receptor involvement. Coincubation with caerulein, galanin, and octreotide significantly reduced the potentiating effect galanin. However, coincubation with the somatostatin receptor antagonist, alone or in combination with galanin, significantly increased caerulein-stimulated amylase secretion to a level comparable to the galanin potentiation. Taken together, these data suggest that, at supramaximal caerulein concentrations, galanin acts via its receptors to further increase caerulein-stimulated amylase secretion by inhibiting the caerulein-induced release of somatostatin.