{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T06:55:26Z","timestamp":1793688926625,"version":"4.5.1"},"reference-count":46,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T00:00:00Z","timestamp":1783900800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["EANM Innovation"],"published-print":{"date-parts":[[2026,9]]},"DOI":"10.1016\/j.eanmi.2026.100288","type":"journal-article","created":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T15:46:33Z","timestamp":1784389593000},"page":"100288","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":2,"special_numbering":"C","title":["SSTR2 receptor states and cellular metabolism modulate 177Lu-DOTATATE binding affinity"],"prefix":"10.1016","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0063-3233","authenticated-orcid":false,"given":"Sara Lundsten","family":"Salomonsson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pleun A.M.","family":"Engbers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Nonnekens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sina","family":"Bondza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.eanmi.2026.100288_bib1","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1038\/s41573-025-01139-y","article-title":"GPCR drug discovery: new agents, targets and indications","volume":"24","author":"Lorente","year":"2025","journal-title":"Nat Rev Drug Discov"},{"key":"10.1016\/j.eanmi.2026.100288_bib2","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1038\/s41573-024-01083-3","article-title":"Functional dynamics of G protein-coupled receptors reveal new routes for drug discovery","volume":"24","author":"Conflitti","year":"2025","journal-title":"Nat Rev Drug Discov"},{"key":"10.1016\/j.eanmi.2026.100288_bib3","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1146\/annurev-biochem-060614-033910","article-title":"The molecular basis of G protein-coupled receptor activation","volume":"87","author":"Weis","year":"2018","journal-title":"Annu Rev Biochem"},{"key":"10.1016\/j.eanmi.2026.100288_bib4","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/j.tips.2011.05.002","article-title":"\u03b2-arrestin-mediated receptor trafficking and signal transduction","volume":"32","author":"Shenoy","year":"2011","journal-title":"Trends Pharmacol Sci"},{"key":"10.1016\/j.eanmi.2026.100288_bib5","doi-asserted-by":"crossref","DOI":"10.1530\/JOE-23-0298","article-title":"Somatostatin receptors and the associated intracellular machinery: the two sides of the coin","volume":"260","author":"Campana","year":"2024","journal-title":"J Endocrinol"},{"key":"10.1016\/j.eanmi.2026.100288_bib6","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.yfrne.2013.07.005","article-title":"Somatostatin receptors: from signaling to clinical practice","volume":"34","author":"Theodoropoulou","year":"2013","journal-title":"Front Neuroendocrinol"},{"key":"10.1016\/j.eanmi.2026.100288_bib7","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1056\/NEJMoa1607427","article-title":"Phase 3 trial of (177)Lu-Dotatate for midgut neuroendocrine tumors","volume":"376","author":"Strosberg","year":"2017","journal-title":"N Engl J Med"},{"key":"10.1016\/j.eanmi.2026.100288_bib8","doi-asserted-by":"crossref","first-page":"4001","DOI":"10.1007\/s00259-025-07246-7","article-title":"Safety and dosimetry of [177Lu]Lu-DOTA-TATE in adolescent patients with somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumours, or pheochromocytomas and paragangliomas: primary analysis of the phase II NETTER-P study","volume":"52","author":"Gaze","year":"2025","journal-title":"Eur J Nucl Med Mol Imag"},{"key":"10.1016\/j.eanmi.2026.100288_bib9","doi-asserted-by":"crossref","first-page":"21374","DOI":"10.1074\/jbc.M313522200","article-title":"Differential \u03b2-arrestin trafficking and endosomal sorting of somatostatin receptor subtypes","volume":"279","author":"Tulipano","year":"2004","journal-title":"J Biol Chem"},{"key":"10.1016\/j.eanmi.2026.100288_bib10","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1007\/s12020-016-1026-2","article-title":"Identification of human somatostatin receptor 2 domains involved in internalization and signaling in QGP-1 pancreatic neuroendocrine tumor cell line","volume":"56","author":"Cambiaghi","year":"2017","journal-title":"Endocrine"},{"key":"10.1016\/j.eanmi.2026.100288_bib11","doi-asserted-by":"crossref","DOI":"10.3389\/fnume.2025.1655419","article-title":"Targeted radionuclide therapy and diagnostic imaging of SSTR positive neuroendocrine tumors: a clinical update in the new decade","volume":"5","author":"Haugh","year":"2025","journal-title":"Front Nucl Med"},{"key":"10.1016\/j.eanmi.2026.100288_bib12","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/sj.bjp.0700858","article-title":"Somatostatin receptors in Neuro2A neuroblastoma cells: operational characteristics","volume":"120","author":"Koenig","year":"1997","journal-title":"Br J Pharmacol"},{"key":"10.1016\/j.eanmi.2026.100288_bib13","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1038\/sj.bjp.0700859","article-title":"Somatostatin receptors in Neuro2A neuroblastoma cells: ligand internalization","volume":"120","author":"Koenig","year":"1997","journal-title":"Br J Pharmacol"},{"issue":"Pt 2","key":"10.1016\/j.eanmi.2026.100288_bib14","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1042\/bj3360291","article-title":"Fates of endocytosed somatostatin sst2 receptors and associated agonists","volume":"336","author":"Koenig","year":"1998","journal-title":"Biochem J"},{"key":"10.1016\/j.eanmi.2026.100288_bib15","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.3390\/ph14121265","article-title":"Distinct in vitro binding profile of the somatostatin receptor subtype 2 antagonist [177 lu]lu-ops201 compared to the agonist [177 lu]lu-dota-tate","volume":"14","author":"Mansi","year":"2021","journal-title":"Pharmaceuticals"},{"key":"10.1016\/j.eanmi.2026.100288_bib16","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1021\/bc049972c","article-title":"Evaluation of cleavable (Tyr3)-octreotate derivatives for longer intracellular probe residence","volume":"15","author":"Whetstone","year":"2004","journal-title":"Bioconjug Chem"},{"key":"10.1016\/j.eanmi.2026.100288_bib17","first-page":"2189","article-title":"Comparison of 111In-DOTA-NOC and 111In-DOTA-TATE distribution in the target and dose-limiting tissues: conflicting results in vitro and in vivo","volume":"28","author":"Cihlo","year":"2008","journal-title":"Anticancer Res"},{"key":"10.1016\/j.eanmi.2026.100288_bib18","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.1007\/s00259-003-1255-5","article-title":"DOTA-NOC, a high-affinity ligand of somatostatin receptor subtypes 2, 3 and 5 for labelling with various radiometals","volume":"30","author":"Wild","year":"2003","journal-title":"Eur J Nucl Med Mol Imag"},{"key":"10.1016\/j.eanmi.2026.100288_bib19","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1038\/s41467-022-28789-5","article-title":"Kinetic model of GPCR-G protein interactions reveals allokairic modulation of signaling","volume":"13","author":"Culhane","year":"2022","journal-title":"Nat Commun"},{"key":"10.1016\/j.eanmi.2026.100288_bib20","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1038\/nrd.2016.123","article-title":"Biophysics in drug discovery: impact, challenges and opportunities","volume":"15","author":"Renaud","year":"2016","journal-title":"Nat Rev Drug Discov"},{"key":"10.1016\/j.eanmi.2026.100288_bib21","article-title":"Latest surface plasmon resonance advances for G protein-coupled receptors","volume":"16","author":"De Soricellis","year":"2025","journal-title":"J Pharm Anal"},{"key":"10.1016\/j.eanmi.2026.100288_bib22","doi-asserted-by":"crossref","first-page":"343","DOI":"10.3892\/mco.2012.37","article-title":"Resolving the EGF-EGFR interaction characteristics through a multiple-temperature, multiple-inhibitor, real-time interaction analysis approach","volume":"1","author":"Bj\u00f6rkelund","year":"2013","journal-title":"Mol Clin Oncol"},{"key":"10.1016\/j.eanmi.2026.100288_bib23","doi-asserted-by":"crossref","DOI":"10.1080\/19420862.2020.1792673","article-title":"Bivalent binding on cells varies between anti-CD20 antibodies and is dose-dependent","volume":"12","author":"Bondza","year":"2020","journal-title":"mAbs"},{"key":"10.1016\/j.eanmi.2026.100288_bib24","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2020.609941","article-title":"Complement-dependent activity of CD20-Specific IgG correlates with bivalent antigen binding and C1q binding strength","volume":"11","author":"Bondza","year":"2021","journal-title":"Front Immunol"},{"key":"10.1016\/j.eanmi.2026.100288_bib25","doi-asserted-by":"crossref","first-page":"1695","DOI":"10.3390\/biom11111695","article-title":"p53-Mediated radiosensitization of 177Lu-DOTATATE in neuroblastoma tumor spheroids","volume":"11","author":"Lundsten","year":"2021","journal-title":"Biomolecules"},{"key":"10.1016\/j.eanmi.2026.100288_bib26","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1038\/s41392-025-02410-9","article-title":"Development of a leucine-rich repeat-containing protein 15-targeted radio-immunotheranostic approach to deplete pro-tumorigenic mechanisms and immunotherapy resistance","volume":"10","author":"Storey","year":"2025","journal-title":"Signal Transduct Targeted Ther"},{"key":"10.1016\/j.eanmi.2026.100288_bib27","doi-asserted-by":"crossref","first-page":"2436","DOI":"10.1021\/acs.molpharmaceut.5c01484","article-title":"Evaluation of RBC targeting as a strategy to extend half-life and reduce nonspecific tissue uptake of biologics","volume":"23","author":"Cho","year":"2026","journal-title":"Mol Pharm"},{"key":"10.1016\/j.eanmi.2026.100288_bib28","doi-asserted-by":"crossref","first-page":"7940","DOI":"10.1038\/s41467-023-43601-8","article-title":"Structural basis of antibody inhibition and chemokine activation of the human CC chemokine receptor 8","volume":"14","author":"Sun","year":"2023","journal-title":"Nat Commun"},{"key":"10.1016\/j.eanmi.2026.100288_bib29","doi-asserted-by":"crossref","first-page":"1821","DOI":"10.7150\/thno.15311","article-title":"Potentiation of peptide receptor radionuclide therapy by the PARP inhibitor olaparib","volume":"6","author":"Nonnekens","year":"2016","journal-title":"Theranostics"},{"key":"10.1016\/j.eanmi.2026.100288_bib30","doi-asserted-by":"crossref","first-page":"2953","DOI":"10.1210\/en.2018-00368","article-title":"Single-molecule microscopy reveals dynamic FLNA interactions governing SSTR2 clustering and internalization","volume":"159","author":"Treppiedi","year":"2018","journal-title":"Endocrinology"},{"key":"10.1016\/j.eanmi.2026.100288_bib31","first-page":"1287","article-title":"The HSP90 inhibitor Onalespib potentiates 177Lu-DOTATATE therapy in neuroendocrine tumor cells","volume":"55","author":"Lundsten","year":"2019","journal-title":"Int J Oncol"},{"key":"10.1016\/j.eanmi.2026.100288_bib32","doi-asserted-by":"crossref","first-page":"13212","DOI":"10.1021\/acs.analchem.7b02983","article-title":"Novel real-time proximity assay for characterizing multiple receptor interactions on living cells","volume":"89","author":"Bondza","year":"2017","journal-title":"Anal Chem"},{"key":"10.1016\/j.eanmi.2026.100288_bib33","series-title":"Patent: methods for the analysis of solid objects","author":"Andersson","year":"2011"},{"key":"10.1016\/j.eanmi.2026.100288_bib34","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0024739","article-title":"Gefitinib induces epidermal growth factor receptor dimers which alters the interaction characteristics with 125I-EGF","volume":"6","author":"Bj\u00f6rkelund","year":"2011","journal-title":"PLoS One"},{"key":"10.1016\/j.eanmi.2026.100288_bib35","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1038\/nmeth.2089","article-title":"NIH image to ImageJ: 25 years of image analysis","volume":"9","author":"Schneider","year":"2012","journal-title":"Nat Methods"},{"key":"10.1016\/j.eanmi.2026.100288_bib36","doi-asserted-by":"crossref","first-page":"17174","DOI":"10.1016\/S0021-9258(17)32537-1","article-title":"Kinetic analysis of the trafficking of muscarinic acetylcholine receptors between the plasma membrane and intracellular compartments","volume":"269","author":"Koenig","year":"1994","journal-title":"J Biol Chem"},{"key":"10.1016\/j.eanmi.2026.100288_bib37","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2110085119","article-title":"The mechanism for ligand activation of the GPCR-G protein complex","volume":"119","author":"Mafi","year":"2022","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1016\/j.eanmi.2026.100288_bib38","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1042\/bj3210561","article-title":"Signalling functions and biochemical properties of pertussis toxin-resistant G-proteins","volume":"321","author":"Fields","year":"1997","journal-title":"Biochem J"},{"key":"10.1016\/j.eanmi.2026.100288_bib39","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1097\/00006231-199803000-00013","article-title":"Internalization of radiolabelled [DTPA0]octreotide and [DOTA0,Tyr3]octreotide: peptides for somatostatin receptor-targeted scintigraphy and radionuclide therapy","volume":"19","author":"De Jong","year":"1998","journal-title":"Nucl Med Commun"},{"key":"10.1016\/j.eanmi.2026.100288_bib40","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/s40658-020-0276-5","article-title":"Cellular dosimetry of [(177)Lu]Lu-DOTA-[Tyr(3)]octreotate radionuclide therapy: the impact of modeling assumptions on the correlation with in vitro cytotoxicity","volume":"7","author":"Tamborino","year":"2020","journal-title":"EJNMMI Phys"},{"key":"10.1016\/j.eanmi.2026.100288_bib41","doi-asserted-by":"crossref","first-page":"743","DOI":"10.2967\/jnumed.119.232934","article-title":"Imaging DNA damage repair in vivo after (177)Lu-DOTATATE therapy","volume":"61","author":"O'Neill","year":"2020","journal-title":"J Nucl Med"},{"key":"10.1016\/j.eanmi.2026.100288_bib42","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1210\/jc.2008-1919","article-title":"Differential effects of octreotide and pasireotide on somatostatin receptor internalization and trafficking in vitro","volume":"94","author":"Lesche","year":"2009","journal-title":"J Clin Endocrinol Metab"},{"key":"10.1016\/j.eanmi.2026.100288_bib43","first-page":"502","article-title":"Internalization of sst 2 , sst 3 , and sst 5 receptors: effects of somatostatin agonists and Antagonists","volume":"47","author":"Cescato","year":"2006","journal-title":"J Nucl Med"},{"key":"10.1016\/j.eanmi.2026.100288_bib44","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1186\/s12964-020-00537-6","article-title":"Unusually persistent G\u03b1i-signaling of the neuropeptide Y2 receptor depletes cellular Gi\/o pools and leads to a Gi-refractory state","volume":"18","author":"Ziffert","year":"2020","journal-title":"Cell Commun Signal"},{"key":"10.1016\/j.eanmi.2026.100288_bib46","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1007\/s00259-021-05564-0","article-title":"Combination of terbium-161 with somatostatin receptor antagonists\u2014a potential paradigm shift for the treatment of neuroendocrine neoplasms","volume":"49","author":"Borgna","year":"2022","journal-title":"Eur J Nucl Med Mol Imag"},{"key":"10.1016\/j.eanmi.2026.100288_bib47","doi-asserted-by":"crossref","first-page":"2517","DOI":"10.1007\/s00259-024-06641-w","article-title":"First-in-human administration of terbium-161-labelled somatostatin receptor subtype 2 antagonist ([161Tb]Tb-DOTA-LM3) in a patient with a metastatic neuroendocrine tumour of the ileum","volume":"51","author":"Fricke","year":"2024","journal-title":"Eur J Nucl Med Mol Imag"}],"container-title":["EANM Innovation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S305129132600265X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S305129132600265X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T13:28:11Z","timestamp":1789565291000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S305129132600265X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9]]},"references-count":46,"alternative-id":["S305129132600265X"],"URL":"https:\/\/doi.org\/10.1016\/j.eanmi.2026.100288","relation":{"has-preprint":[{"id-type":"doi","id":"10.22541\/au.177513701.16570514\/v1","asserted-by":"object"}]},"ISSN":["3051-2913"],"issn-type":[{"value":"3051-2913","type":"print"}],"subject":[],"published":{"date-parts":[[2026,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"SSTR2 receptor states and cellular metabolism modulate 177Lu-DOTATATE binding affinity","name":"articletitle","label":"Article Title"},{"value":"EANM Innovation","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.eanmi.2026.100288","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Authors. Published by Elsevier B.V. on behalf of European Association of Nuclear Medicine (EANM).","name":"copyright","label":"Copyright"}],"article-number":"100288"}}