Paltusotine versus octreotide: different effects on radioligand uptake in neuroendocrine tumours

Somatostatin receptor analogues are well-established in the treatment of metastatic gastro-enteropancreatic neuroendocrine tumours (GEP-NETs), especially for symptom control in patients with the carcinoid syndrome, and to control tumour growth. However, they need to be discontinued before peptide receptor radionuclide therapy (PRRT) as they may saturate the somatostatin receptor 2 (SSTR2) and prevent binding of the radioactive ligand.

We evaluated the effects of the novel somatostatin analogue paltusotine on ¹⁸F-SiTATE radioligand uptake and on GEP-NET cell viability in comparison to octreotide.

Paltusotine and octreotide were evaluated in varying concentrations in an ¹⁸F-SiTATE uptake assay using stable hSSTR2 over-expressing BON-1 cells, and in a cell viability assay utilising different NET cell lines and human patient-derived GEP-NET primary cultures (n = 13).

Low, clinically-relevant concentrations of paltusotine (7.3-25.4 nM) demonstrated no influence on cellular radioligand uptake compared to the control. In contrast, octreotide reduced radioligand uptake at low, clinically-relevant concentrations (7.3-25.4 nM) and led to a further significant reduction of radioligand uptake at higher concentrations (73-508 nM). Both paltusotine and octreotide showed overall little or no significant anti-tumour effects in vitro in NET cell lines. However, in contrast to octreotide, paltusotine led to a slight decrease in cell viability of patient-derived GEP-NET primary cultures.

Treatment with paltusotine did not significantly reduce radioligand binding of ¹⁸F-SiTATE in vitro, indicating no influence on SSTR2 targeting. This might enable a continuation of somatostatin receptor analogue therapy with paltusotine during PRRT, potentially improving symptom control in GEP-NET patients with the carcinoid syndrome.