{"entity":{"id":"idea-net-antagonist-ligands","kind":"idea","name":"SSTR antagonist radioligands to increase tumour dose","aka":[],"tldr":"Radioligand therapy for neuroendocrine tumours built on somatostatin receptor antagonists rather than the agonists used today: antagonists bind the receptor in every state and are not internalised, so they occupy several times more sites per cell and deliver more radiation per dose. The test is a randomised phase 2 against agonist lutetium therapy.","summary":"The idea is to build peptide receptor radionuclide therapy for neuroendocrine tumours on somatostatin receptor 2 antagonists rather than the agonists used today. Antagonists bind receptors in every conformational state and are not internalised, so they occupy several times more binding sites on each cell and deliver more radiation per dose. First-in-human studies of the antagonist 177Lu-satoreotide tetraxetan showed higher tumour uptake and dose than agonists, and early trials report responses in patients refractory to agonist PRRT. The hypothesis is higher response rates at an equivalent renal dose, including in tumours with low SSTR2 expression; the test is a randomised phase 2 of antagonist versus agonist 177Lu-PRRT in grade 1 to 2 gastroenteropancreatic NETs.","asOf":"2026-09-07","links":[{"label":"Reidy-Lagunes et al., Phase 1 trial of the SSTR antagonist radioligand 177Lu-satoreotide tetraxetan in neuroendocrine tumours (Clinical Cancer Research 2019)","url":"https://doi.org/10.1158/1078-0432.CCR-19-1026"}],"tags":[],"related":[],"cancers":["neuroendocrine"],"sections":[],"technologies":["prrt"],"targets":["sstr2"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["alphamedix-02","compete","nct04919226"],"people":[],"bottlenecks":[],"keyPapers":["paper-reidy-lagunes-clin-cancer-res"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Antagonist PRRT achieves higher response rates than agonist PRRT at equivalent renal dose, including in low-SSTR-expressing tumours.","rationale":"Antagonists bind receptors in all conformational states and are not internalised, increasing binding sites several-fold.","test":"Randomised phase 2 antagonist vs agonist 177Lu-PRRT in grade 1-2 GEP-NETs.","maturity":"early-clinical"},"route":"/ideas/idea-net-antagonist-ligands/","neighbours":{"cancer":[{"id":"neuroendocrine","kind":"cancer","name":"Neuroendocrine tumours","route":"/cancers/neuroendocrine/"},{"id":"small-intestinal-net","kind":"cancer","name":"Small intestinal neuroendocrine tumours","route":"/cancers/small-intestinal-net/"}],"technology":[{"id":"prrt","kind":"technology","name":"Peptide receptor radionuclide therapy (PRRT)","route":"/technologies/prrt/"}],"target":[{"id":"sstr2","kind":"target","name":"Somatostatin receptor 2","route":"/targets/sstr2/"}],"trial":[{"id":"alphamedix-02","kind":"trial","name":"ALPHAMEDIX-02","route":"/trials/alphamedix-02/"},{"id":"compete","kind":"trial","name":"COMPETE","route":"/trials/compete/"},{"id":"nct04919226","kind":"trial","name":"Lutetium 177Lu-Edotreotide Versus Best Standard of Care in Well-differentiated Aggressive Grade-2 and Grade-3 GastroEnteroPancreatic NeuroEndocrine Tumors (GEP-NETs) - COMPOSE","route":"/trials/nct04919226/"}],"paper":[{"id":"paper-reidy-lagunes-clin-cancer-res","kind":"paper","name":"Phase I Trial of Well-Differentiated Neuroendocrine Tumors (NETs) with Radiolabeled Somatostatin Antagonist 177 Lu-Satoreotide Tetraxetan","route":"/key-papers/paper-reidy-lagunes-clin-cancer-res/"}]}}