{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T08:03:41Z","timestamp":1791187421686,"version":"4.1.0"},"reference-count":38,"publisher":"American Diabetes Association","issue":"10","content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2014,10,1]]},"abstract":"<jats:p>In humans, a well-developed serotonin system is localized to the pancreatic islets while being absent in exocrine pancreas. Assessment of pancreatic serotonin biosynthesis could therefore be used to estimate the human endocrine pancreas. Proof of concept was tested in a prospective clinical trial by comparisons of type 1 diabetic (T1D) patients, with extensive reduction of \u03b2-cells, with healthy volunteers (HVs). C-peptide\u2013negative (i.e., insulin-deficient) T1D subjects (n = 10) and HVs (n = 9) underwent dynamic positron emission tomography with the radiolabeled serotonin precursor [11C]5-hydroxy-tryptophan ([11C]5-HTP). A significant accumulation of [11C]5-HTP was obtained in the pancreas of the HVs, with large interindividual variation. A substantial and highly significant reduction (66%) in the pancreatic uptake of [11C]5-HTP in T1D subjects was observed, and this was most evident in the corpus and caudal regions of the pancreas where \u03b2-cells normally are the major constituent of the islets. [11C]5-HTP retention in the pancreas was reduced in T1D compared with nondiabetic subjects. Accumulation of [11C]5-HTP in the pancreas of both HVs and subjects with T1D was in agreement with previously reported morphological observations on the \u03b2-cell volume, implying that [11C]5-HTP retention is a useful noninvasive surrogate marker for the human endocrine pancreas.<\/jats:p>","DOI":"10.2337\/db13-1877","type":"journal-article","created":{"date-parts":[[2014,5,22]],"date-time":"2014-05-22T06:39:32Z","timestamp":1400740772000},"page":"3428-3437","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":62,"title":["Positron Emission Tomography Ligand [11C]5-Hydroxy-Tryptophan Can Be Used as a Surrogate Marker for the Human Endocrine Pancreas"],"prefix":"10.2337","volume":"63","author":[{"given":"Olof","family":"Eriksson","sequence":"first","affiliation":[{"name":"Department of Medicinal Chemistry, Preclinical PET Platform, Uppsala University, Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Espes","sequence":"additional","affiliation":[{"name":"Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ram K.","family":"Selvaraju","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, Preclinical PET Platform, Uppsala University, Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Jansson","sequence":"additional","affiliation":[{"name":"Department of Radiology, Oncology, and Radiation Sciences, Uppsala University, Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunnar","family":"Antoni","sequence":"additional","affiliation":[{"name":"Department of Radiology, Oncology, and Radiation Sciences, Uppsala University, Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"S\u00f6rensen","sequence":"additional","affiliation":[{"name":"Department of Radiology, Oncology, and Radiation Sciences, Uppsala University, Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Lubberink","sequence":"additional","affiliation":[{"name":"Department of Radiology, Oncology, and Radiation Sciences, Uppsala University, Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali-Reza","family":"Biglarnia","sequence":"additional","affiliation":[{"name":"Department of Surgical Sciences, Uppsala University, Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan W.","family":"Eriksson","sequence":"additional","affiliation":[{"name":"AstraZeneca R&D, M\u00f6lndal, Sweden"},{"name":"Department of Medical Sciences, Uppsala University, Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders","family":"Sundin","sequence":"additional","affiliation":[{"name":"Department of Radiology, Oncology, and Radiation Sciences, Uppsala University, Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e5kan","family":"Ahlstr\u00f6m","sequence":"additional","affiliation":[{"name":"Department of Radiology, Oncology, and Radiation Sciences, Uppsala University, Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbro","family":"Eriksson","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Uppsala University, Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Johansson","sequence":"additional","affiliation":[{"name":"Department of Radiology, Oncology, and Radiation Sciences, Uppsala University, Uppsala, Sweden"},{"name":"AstraZeneca R&D, M\u00f6lndal, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Per-Ola","family":"Carlsson","sequence":"additional","affiliation":[{"name":"Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden"},{"name":"Department of Medical Sciences, Uppsala University, Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olle","family":"Korsgren","sequence":"additional","affiliation":[{"name":"Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2014,9,15]]},"reference":[{"key":"2022031211085165900_B1","doi-asserted-by":"crossref","first-page":"908","DOI":"10.2967\/jnumed.111.100545","article-title":"In vivo imaging of endogenous pancreatic \u03b2-cell mass in healthy and type 1 diabetic subjects using 18F-fluoropropyl-dihydrotetrabenazine and PET","volume":"53","author":"Normandin","year":"2012","journal-title":"J Nucl Med"},{"key":"2022031211085165900_B2","doi-asserted-by":"crossref","first-page":"382","DOI":"10.2967\/jnumed.108.054866","article-title":"11C-dihydrotetrabenazine PET of the pancreas in subjects with long-standing type 1 diabetes and in healthy controls","volume":"50","author":"Goland","year":"2009","journal-title":"J Nucl Med"},{"key":"2022031211085165900_B3","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1007\/s00125-012-2491-7","article-title":"Obstacles on the way to the clinical visualisation of beta cells: looking for the Aeneas of molecular imaging to navigate between Scylla and Charybdis","volume":"55","author":"Andralojc","year":"2012","journal-title":"Diabetologia"},{"key":"2022031211085165900_B4","doi-asserted-by":"crossref","first-page":"1458","DOI":"10.2967\/jnumed.112.114066","article-title":"In vivo imaging of the glucagonlike peptide 1 receptor in the pancreas with 68Ga-labeled DO3A-exendin-4","volume":"54","author":"Selvaraju","year":"2013","journal-title":"J Nucl Med"},{"key":"2022031211085165900_B5","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1007\/s00125-014-3166-3","article-title":"Non-invasive quantification of the beta cell mass by SPECT with \u00b9\u00b9\u00b9In-labelled exendin","volume":"57","author":"Brom","year":"2014","journal-title":"Diabetologia"},{"key":"2022031211085165900_B6","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/S0925-4773(02)00333-7","article-title":"Gene expression cascades in pancreatic development","volume":"120","author":"Wilson","year":"2003","journal-title":"Mech Dev"},{"key":"2022031211085165900_B7","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1111\/j.1399-0004.2005.00534.x","article-title":"Molecular genetics of the early development of hindbrain serotonergic neurons","volume":"68","author":"Cordes","year":"2005","journal-title":"Clin Genet"},{"key":"2022031211085165900_B8","doi-asserted-by":"crossref","first-page":"3208","DOI":"10.2337\/db10-1192","article-title":"Convergence of the insulin and serotonin programs in the pancreatic \u03b2-cell","volume":"60","author":"Ohta","year":"2011","journal-title":"Diabetes"},{"key":"2022031211085165900_B9","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1007\/BF01219468","article-title":"Monoamines in the pancreatic islets of the mouse. Subcellular localization of 5-hydroxytryptamine by electron microscopic autoradiography","volume":"7","author":"Ekholm","year":"1971","journal-title":"Diabetologia"},{"key":"2022031211085165900_B10","doi-asserted-by":"crossref","first-page":"304","DOI":"10.2337\/diab.29.4.304","article-title":"Pancreatic islets: a tissue rich in serotonin","volume":"29","author":"Bird","year":"1980","journal-title":"Diabetes"},{"key":"2022031211085165900_B11","doi-asserted-by":"crossref","first-page":"2589","DOI":"10.1007\/s00125-010-1913-7","article-title":"Placental lactogens induce serotonin biosynthesis in a subset of mouse beta cells during pregnancy","volume":"53","author":"Schraenen","year":"2010","journal-title":"Diabetologia"},{"key":"2022031211085165900_B12","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1007\/BF00318765","article-title":"Phylogenetic study of serotonin-immunoreactive structures in the pancreas of various vertebrates","volume":"263","author":"Ding","year":"1991","journal-title":"Cell Tissue Res"},{"key":"2022031211085165900_B13","doi-asserted-by":"crossref","first-page":"e1000229","DOI":"10.1371\/journal.pbio.1000229","article-title":"Intracellular serotonin modulates insulin secretion from pancreatic beta-cells by protein serotonylation","volume":"7","author":"Paulmann","year":"2009","journal-title":"PLoS Biol"},{"key":"2022031211085165900_B14","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1038\/nm.2173","article-title":"Serotonin regulates pancreatic beta cell mass during pregnancy","volume":"16","author":"Kim","year":"2010","journal-title":"Nat Med"},{"key":"2022031211085165900_B15","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1002\/syn.20268","article-title":"Validation studies on the 5-hydroxy-L-[beta-11C]-tryptophan\/PET method for probing the decarboxylase step in serotonin synthesis","volume":"59","author":"Lundquist","year":"2006","journal-title":"Synapse"},{"key":"2022031211085165900_B16","doi-asserted-by":"crossref","first-page":"2534","DOI":"10.1200\/JCO.1998.16.7.2534","article-title":"Positron emission tomography with 5-hydroxytryprophan in neuroendocrine tumors","volume":"16","author":"Orlefors","year":"1998","journal-title":"J Clin Oncol"},{"key":"2022031211085165900_B17","doi-asserted-by":"crossref","first-page":"3392","DOI":"10.1210\/jc.2004-1938","article-title":"Whole-body (11)C-5-hydroxytryptophan positron emission tomography as a universal imaging technique for neuroendocrine tumors: comparison with somatostatin receptor scintigraphy and computed tomography","volume":"90","author":"Orlefors","year":"2005","journal-title":"J Clin Endocrinol Metab"},{"key":"2022031211085165900_B18","doi-asserted-by":"crossref","first-page":"460","DOI":"10.2967\/jnumed.113.125187","article-title":"Quantitative imaging of serotonergic biosynthesis and degradation in the endocrine pancreas","volume":"55","author":"Eriksson","year":"2014","journal-title":"J Nucl Med"},{"key":"2022031211085165900_B19","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1016\/j.nucmedbio.2013.02.005","article-title":"5-Fluoro-[\u03b2-\u00b9\u00b9C]-L-tryptophan is a functional analogue of 5-hydroxy-[\u03b2-\u00b9\u00b9C]-L-tryptophan in vitro but not in vivo","volume":"40","author":"Eriksson","year":"2013","journal-title":"Nucl Med Biol"},{"key":"2022031211085165900_B20","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1210\/endo-93-4-932","article-title":"Amino acid conversion into 5-hydroxytryptamine in pancreatic beta-cells","volume":"93","author":"Gylfe","year":"1973","journal-title":"Endocrinology"},{"key":"2022031211085165900_B21","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1210\/endo-83-5-917","article-title":"Electron microscopic cytochemistry of 5-hydroxytryptamine (5-HT) in the beta cells of guinea pig endocrine pancreas","volume":"83","author":"Jaim-Etcheverry","year":"1968","journal-title":"Endocrinology"},{"key":"2022031211085165900_B22","doi-asserted-by":"crossref","first-page":"1755","DOI":"10.2967\/jnumed.112.104117","article-title":"11C-hydroxytryptophan uptake and metabolism in endocrine and exocrine pancreas","volume":"53","author":"Di Gialleonardo","year":"2012","journal-title":"J Nucl Med"},{"key":"2022031211085165900_B23","doi-asserted-by":"crossref","first-page":"E457","DOI":"10.1152\/ajpendo.00044.2002","article-title":"Glucose-induced islet blood flow increase in rats: interaction between nervous and metabolic mediators","volume":"283","author":"Carlsson","year":"2002","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"2022031211085165900_B24","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1007\/s00259-005-1891-z","article-title":"Carbidopa pretreatment improves image interpretation and visualisation of carcinoid tumours with 11C-5-hydroxytryptophan positron emission tomography","volume":"33","author":"Orlefors","year":"2006","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"2022031211085165900_B25","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1097\/00004728-198909000-00021","article-title":"Quantitation of myocardial blood flow with H2 15O and positron emission tomography: assessment and error analysis of a mathematical approach","volume":"13","author":"Herrero","year":"1989","journal-title":"J Comput Assist Tomogr"},{"key":"2022031211085165900_B26","doi-asserted-by":"crossref","first-page":"1661","DOI":"10.1038\/labinvest.2010.124","article-title":"Quantitative analysis of cell composition and purity of human pancreatic islet preparations","volume":"90","author":"Pisania","year":"2010","journal-title":"Lab Invest"},{"key":"2022031211085165900_B27","doi-asserted-by":"crossref","first-page":"1498","DOI":"10.1038\/1841498a0","article-title":"Actual distribution of the number and volume of the islets of Langerhans in different size classes in non-diabetic humans of varying ages","volume":"184","author":"Hellman","year":"1959","journal-title":"Nature"},{"key":"2022031211085165900_B28","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1007\/BF00251826","article-title":"Cellular composition of the human diabetic pancreas","volume":"24","author":"Rahier","year":"1983","journal-title":"Diabetologia"},{"key":"2022031211085165900_B29","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1111\/j.1463-1326.2008.00969.x","article-title":"Pancreatic beta-cell mass in European subjects with type 2 diabetes","volume":"10","author":"Rahier","year":"2008","journal-title":"Diabetes Obes Metab"},{"key":"2022031211085165900_B30","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1007\/s005920170012","article-title":"Pancreatic volume in type 1 and type 2 diabetes mellitus","volume":"38","author":"Goda","year":"2001","journal-title":"Acta Diabetol"},{"key":"2022031211085165900_B31","doi-asserted-by":"crossref","first-page":"E2109","DOI":"10.1210\/jc.2012-1815","article-title":"Pancreatic volume is reduced in adult patients with recently diagnosed type 1 diabetes","volume":"97","author":"Williams","year":"2012","journal-title":"J Clin Endocrinol Metab"},{"key":"2022031211085165900_B32","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.1007\/s00125-009-1406-8","article-title":"Pancreatic perfusion of healthy individuals and type 1 diabetic patients as assessed by magnetic resonance perfusion imaging","volume":"52","author":"Hirshberg","year":"2009","journal-title":"Diabetologia"},{"key":"2022031211085165900_B33","doi-asserted-by":"crossref","first-page":"4513","DOI":"10.1210\/en.2004-0691","article-title":"Identification of tissue-restricted transcripts in human islets","volume":"145","author":"Maffei","year":"2004","journal-title":"Endocrinology"},{"key":"2022031211085165900_B34","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/2191-219X-1-33","article-title":"Decreased defluorination using the novel beta-cell imaging agent [18F]FE-DTBZ-d4 in pigs examined by PET","volume":"1","author":"Jahan","year":"2011","journal-title":"EJNMMI Res"},{"key":"2022031211085165900_B35","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.2967\/jnumed.109.074492","article-title":"Assessment of islet specificity of dihydrotetrabenazine radiotracer binding in rat pancreas and human pancreas","volume":"51","author":"Fagerholm","year":"2010","journal-title":"J Nucl Med"},{"key":"2022031211085165900_B36","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/j.nucmedbio.2009.12.004","article-title":"In vivo and in vitro characterization of [18F]-FE-(+)-DTBZ as a tracer for beta-cell mass","volume":"37","author":"Eriksson","year":"2010","journal-title":"Nucl Med Biol"},{"key":"2022031211085165900_B37","doi-asserted-by":"crossref","first-page":"20719","DOI":"10.1073\/pnas.1109480108","article-title":"Multimodal image coregistration and inducible selective cell ablation to evaluate imaging ligands","volume":"108","author":"Virostko","year":"2011","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2022031211085165900_B38"}],"container-title":["Diabetes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.org\/diabetes\/diabetes\/article-pdf\/63\/10\/3428\/572636\/3428.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article-pdf\/63\/10\/3428\/572636\/3428.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T16:40:11Z","timestamp":1667407211000},"score":1,"resource":{"primary":{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article\/63\/10\/3428\/17617\/Positron-Emission-Tomography-Ligand-11C-5-Hydroxy"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,9,15]]},"references-count":38,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2014,9,15]]},"published-print":{"date-parts":[[2014,10,1]]}},"URL":"https:\/\/doi.org\/10.2337\/db13-1877","relation":{},"ISSN":["0012-1797","1939-327X"],"issn-type":[{"value":"0012-1797","type":"print"},{"value":"1939-327X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,9,15]]}}}