{"entity":{"id":"norepinephrine-transporter","kind":"target","name":"Norepinephrine transporter (NET)","aka":["NET","Noradrenaline transporter"],"tldr":"A protein on nerve cells and adrenal-type tumour cells that pulls noradrenaline back inside after it has been released. A radioactive drug called MIBG looks and acts enough like noradrenaline that this same protein carries it into neuroblastoma and phaeochromocytoma cells, so doctors can see or treat the tumour.","summary":"The norepinephrine transporter is a 12-transmembrane-domain protein of presynaptic sympathetic neurons and adrenal medullary chromaffin cells that terminates noradrenergic signalling by taking norepinephrine back into the cell (uptake-1), an active, sodium- and chloride-dependent, ATP-driven process roughly 50-fold more efficient than passive diffusion. Once inside, norepinephrine (and NET's synthetic analogue metaiodobenzylguanidine, MIBG) can be stored in secretory vesicles via the vesicular monoamine transporters (VMAT1/2) or remain in the cytoplasm.\n\nTumours that arise from sympathetic neural crest precursors - neuroblastoma, phaeochromocytoma and paraganglioma - retain NET expression at high frequency (around 90% of neuroblastomas are NET-positive), and expression correlates with MIBG avidity on imaging. Radioiodinated MIBG (123I for diagnosis, 131I for therapy) is taken up through NET, giving both a diagnostic scan and, at therapeutic activities, a targeted radiotherapy. Other transporters (OCT1-3, MATE1/2-K) contribute to non-specific uptake into liver, salivary gland and heart and to renal clearance, and drugs that block NET (tricyclic antidepressants, some stimulants) must be stopped before MIBG scanning or therapy because they blunt tumour uptake.\n\nAs a target, NET's strength is high, tumour-restricted expression in an otherwise hard-to-image tumour family, plus intracellular retention via VMAT once inside the cell. Its main limitations are heterogeneous expression (MYCN-amplified, poorly differentiated neuroblastomas tend to have lower NET expression and are less MIBG-avid) and competition from other transporters that reduce specificity and complicate dosimetry.","asOf":"2026-09-22","links":[{"label":"DMD: clinical applications and roles of transporters in disposition, tumour targeting and tissue toxicity of MIBG","url":"https://dmd.aspetjournals.org/content/50/9/1218"},{"label":"JNM (SNMMI supplement): norepinephrine transporter as a target for imaging and therapy","url":"https://jnm.snmjournals.org/content/58/Supplement_2/39S"},{"label":"PMC: 'Nothing but NET' - NET expression and efficacy of 131I-MIBG therapy","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC4237663/"}],"tags":["neuroendocrine","paediatric","transporter"],"related":["i131-mibg","iobenguane-i-131","mibg-theranostics","pheochromocytoma-paraganglioma","neuroblastoma","neuroblastoma-high-risk","metastatic-ppgl","hereditary-ppgl","idea-mfbg-pet-replaces-mibg","nct04724369","paper-pryma-high-specific-activity-i131-mibg-ppgl-jnm-2019","i-123","i-131"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"SLC6A2","biology":"A presynaptic membrane transporter that takes norepinephrine back into sympathetic neurons and adrenal chromaffin cells after release, an active sodium- and chloride-dependent process. Tumours arising from sympathetic neural crest precursors (neuroblastoma, phaeochromocytoma, paraganglioma) retain this transporter at high frequency, allowing the norepinephrine analogue MIBG to be carried into tumour cells for imaging and therapy.","whereFound":["Neuroblastoma: NET-positive in roughly 90% of tumours; MYCN-amplified tumours tend to have lower expression","Phaeochromocytoma and paraganglioma: NET expressed in chromaffin-derived tumour cells, uptake reinforced by VMAT storage","Normal sympathetic nerve terminals and adrenal medulla: physiological expression"],"targetClass":"other","prevalence":[]},"route":"/targets/norepinephrine-transporter/","neighbours":{"drug":[{"id":"i131-mibg","kind":"drug","name":"131I-MIBG (iobenguane I-131) therapy","route":"/drugs/i131-mibg/"},{"id":"iobenguane-i-131","kind":"drug","name":"Iobenguane I-131 (therapeutic)","route":"/drugs/iobenguane-i-131/"}],"technology":[{"id":"mibg-theranostics","kind":"technology","name":"MIBG imaging and 131I-MIBG therapy","route":"/technologies/mibg-theranostics/"}],"indication":[{"id":"hereditary-ppgl","kind":"indication","name":"Hereditary pheochromocytoma and paraganglioma (SDHx, VHL, RET, NF1, MAX and TMEM127)","route":"/indications/hereditary-ppgl/"},{"id":"neuroblastoma-high-risk","kind":"indication","name":"High-risk neuroblastoma","route":"/indications/neuroblastoma-high-risk/"},{"id":"metastatic-ppgl","kind":"indication","name":"Metastatic pheochromocytoma and paraganglioma","route":"/indications/metastatic-ppgl/"},{"id":"neuroblastoma","kind":"indication","name":"Neuroblastoma (paediatric)","route":"/indications/neuroblastoma/"},{"id":"pheochromocytoma-paraganglioma","kind":"indication","name":"Pheochromocytoma and paraganglioma (PPGL)","route":"/indications/pheochromocytoma-paraganglioma/"}],"idea":[{"id":"idea-mfbg-pet-replaces-mibg","kind":"idea","name":"18F-MFBG PET replacing 123I-MIBG scintigraphy","route":"/ideas/idea-mfbg-pet-replaces-mibg/"}],"trial":[{"id":"nct04724369","kind":"trial","name":"Open-Label Study of 18F-mFBG for Imaging Neuroblastoma","route":"/trials/nct04724369/"}],"paper":[{"id":"paper-pryma-high-specific-activity-i131-mibg-ppgl-jnm-2019","kind":"paper","name":"Efficacy and safety of high-specific-activity 131I-MIBG therapy in advanced pheochromocytoma or paraganglioma","route":"/key-papers/paper-pryma-high-specific-activity-i131-mibg-ppgl-jnm-2019/"}],"isotope":[{"id":"i-123","kind":"isotope","name":"Iodine-123","route":"/isotopes/i-123/"},{"id":"i-131","kind":"isotope","name":"Iodine-131","route":"/isotopes/i-131/"}]}}