{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T01:43:14Z","timestamp":1779154994368,"version":"3.51.4"},"reference-count":48,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,5,11]],"date-time":"2017-05-11T00:00:00Z","timestamp":1494460800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,5,11]],"date-time":"2017-05-11T00:00:00Z","timestamp":1494460800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>There is an ongoing search for new tracers to optimize imaging of beta cell-derived tumors (insulinomas). The PAC1 receptor, expressed by insulinomas, can be used for targeting of these tumors. Here, we investigated whether radiolabeled maxadilan could be used for insulinoma imaging. Maxadilan was C- or N-terminally conjugated with DTPA (termed maxadilan-DPTA or DTPA-maxadilan respectively). BALB\/c nude mice bearing subcutaneous INS-1 tumors were injected with either In-111-labeled maxadilan-DTPA or In-111-DTPA-maxadilan. Biodistribution studies were carried out at 1, 2 and 4\u2009hours after injection and SPECT\/CT imaging 1 and 4\u2009hours after injection of maxadilan-DTPA-<jats:sup>111<\/jats:sup>In. Radiolabeling of maxadilan-DTPA (680\u2009MBq\/nmol) was more efficient than of DTPA-maxadilan (55\u2009MBq\/nmol). Conjugation with DTPA slightly reduced receptor binding affinity <jats:italic>in vitro<\/jats:italic>: IC<jats:sub>50<\/jats:sub> values were 3.2, 21.0 and 21.0\u2009nM for maxadilan, <jats:sup>nat<\/jats:sup>In-DTPA-maxadilan and maxadilan-DTPA-<jats:sup>nat<\/jats:sup>In respectively. Upon i.v. injection maxadilan-DTPA-<jats:sup>111<\/jats:sup>In accumulated specifically in INS-1 tumors (7.30\u2009\u00b1\u20091.87%ID\/g) and in the pancreas (3.82\u2009\u00b1\u20090.22%ID\/g). INS-1 tumors were clearly visualized by small animal SPECT\/CT. In conclusion, this study showed that the high affinity of maxadilan to the PAC1 receptor was maintained after DTPA conjugation. Furthermore, radiolabeled maxadilan-DTPA accumulated specifically in INS-1 tumors and, therefore, may qualify as a useful tracer to image insulinomas.<\/jats:p>","DOI":"10.1038\/s41598-017-01852-8","type":"journal-article","created":{"date-parts":[[2017,5,5]],"date-time":"2017-05-05T10:56:50Z","timestamp":1493981810000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Preclinical evaluation of PAC1 targeting with radiolabeled Maxadilan"],"prefix":"10.1038","volume":"7","author":[{"given":"Lieke","family":"Joosten","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5755-1477","authenticated-orcid":false,"given":"Maarten","family":"Brom","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin K. H.","family":"Sch\u00e4fer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Otto C.","family":"Boerman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eberhard","family":"Weihe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Gotthardt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2017,5,11]]},"reference":[{"key":"1852_CR1","doi-asserted-by":"publisher","first-page":"R147","DOI":"10.1530\/EJE-13-1012","volume":"170","author":"P Iglesias","year":"2014","unstructured":"Iglesias, P. & Diez, J. J. Management of endocrine disease: a clinical update on tumor-induced hypoglycemia. European journal of endocrinology\/European Federation of Endocrine Societies. \n                           170, R147\u2013157 (2014).","journal-title":"European journal of endocrinology\/European Federation of Endocrine Societies."},{"key":"1852_CR2","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1016\/S0921-4410(04)22021-X","volume":"22","author":"D Granberg","year":"2005","unstructured":"Granberg, D. & Oberg, K. Neuroendocrine tumours. Cancer chemotherapy and biological response modifiers. \n                           22, 471\u2013483 (2005).","journal-title":"Cancer chemotherapy and biological response modifiers."},{"key":"1852_CR3","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1053\/gast.1997.v112.pm9024313","volume":"112","author":"IM Modlin","year":"1997","unstructured":"Modlin, I. M. & Tang, L. H. Approaches to the diagnosis of gut neuroendocrine tumors: the last word (today). Gastroenterology. \n                           112, 583\u2013590 (1997).","journal-title":"Gastroenterology."},{"key":"1852_CR4","doi-asserted-by":"publisher","first-page":"781","DOI":"10.1007\/s00259-003-1184-3","volume":"30","author":"JC Reubi","year":"2003","unstructured":"Reubi, J. C. & Waser, B. Concomitant expression of several peptide receptors in neuroendocrine tumours: molecular basis for in vivo multireceptor tumour targeting. European journal of nuclear medicine and molecular imaging. \n                           30, 781\u2013793 (2003).","journal-title":"European journal of nuclear medicine and molecular imaging."},{"key":"1852_CR5","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.beem.2016.01.003","volume":"30","author":"T Baumann","year":"2016","unstructured":"Baumann, T., Rottenburger, C., Nicolas, G. & Wild, D. Gastroenteropancreatic neuroendocrine tumours (GEP-NET) - Imaging and staging. Best practice & research. Clinical endocrinology & metabolism. \n                           30, 45\u201357 (2016).","journal-title":"Best practice & research. Clinical endocrinology & metabolism."},{"key":"1852_CR6","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1159\/000367850","volume":"101","author":"L Bodei","year":"2015","unstructured":"Bodei, L. et al. The status of neuroendocrine tumor imaging: from darkness to light? Neuroendocrinology. \n                           101, 1\u201317 (2015).","journal-title":"Neuroendocrinology."},{"key":"1852_CR7","doi-asserted-by":"publisher","first-page":"1593","DOI":"10.1007\/s00259-016-3331-7","volume":"43","author":"V Prasad","year":"2016","unstructured":"Prasad, V. et al. Role of (68)Ga somatostatin receptor PET\/CT in the detection of endogenous hyperinsulinaemic focus: an explorative study. European journal of nuclear medicine and molecular imaging. \n                           43, 1593\u20131600 (2016).","journal-title":"European journal of nuclear medicine and molecular imaging."},{"key":"1852_CR8","first-page":"69","volume":"60","author":"P Sharma","year":"2016","unstructured":"Sharma, P. et al. Somatostatin receptor based PET\/CT imaging with 68 Ga-DOTA-Nal3-octreotide for localization of clinically and biochemically suspected insulinoma. The quarterly journal of nuclear medicine and molecular imaging: official publication of the Italian Association of Nuclear Medicine. \n                           60, 69\u201376 (2016).","journal-title":"The quarterly journal of nuclear medicine and molecular imaging: official publication of the Italian Association of Nuclear Medicine."},{"key":"1852_CR9","doi-asserted-by":"publisher","first-page":"1345","DOI":"10.1007\/s00259-009-1363-y","volume":"37","author":"M Brom","year":"2010","unstructured":"Brom, M. et al. 68Ga-labelled exendin-3, a new agent for the detection of insulinomas with PET. European journal of nuclear medicine and molecular imaging. \n                           37, 1345\u20131355 (2010).","journal-title":"European journal of nuclear medicine and molecular imaging."},{"key":"1852_CR10","first-page":"2025","volume":"47","author":"D Wild","year":"2006","unstructured":"Wild, D. et al. [Lys40(Ahx-DTPA-111In)NH2]exendin-4, a very promising ligand for glucagon-like peptide-1 (GLP-1) receptor targeting. Journal of nuclear medicine: official publication, Society of Nuclear Medicine. \n                           47, 2025\u20132033 (2006).","journal-title":"Journal of nuclear medicine: official publication, Society of Nuclear Medicine."},{"key":"1852_CR11","doi-asserted-by":"publisher","first-page":"1059","DOI":"10.2967\/jnumed.110.074914","volume":"51","author":"D Wild","year":"2010","unstructured":"Wild, D. et al. Exendin-4-based radiopharmaceuticals for glucagonlike peptide-1 receptor PET\/CT and SPECT\/CT. Journal of nuclear medicine: official publication, Society of Nuclear Medicine. \n                           51, 1059\u20131067 (2010).","journal-title":"Journal of nuclear medicine: official publication, Society of Nuclear Medicine."},{"key":"1852_CR12","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/S2213-8587(13)70049-4","volume":"1","author":"E Christ","year":"2013","unstructured":"Christ, E. et al. Glucagon-like peptide-1 receptor imaging for the localisation of insulinomas: a prospective multicentre imaging study. The lancet. Diabetes & endocrinology. \n                           1, 115\u2013122 (2013).","journal-title":"The lancet. Diabetes & endocrinology."},{"key":"1852_CR13","doi-asserted-by":"publisher","first-page":"4398","DOI":"10.1210\/jc.2009-1082","volume":"94","author":"E Christ","year":"2009","unstructured":"Christ, E. et al. Glucagon-like peptide-1 receptor imaging for localization of insulinomas. The Journal of clinical endocrinology and metabolism. \n                           94, 4398\u20134405 (2009).","journal-title":"The Journal of clinical endocrinology and metabolism."},{"key":"1852_CR14","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1007\/s00259-012-2299-1","volume":"40","author":"A Sowa-Staszczak","year":"2013","unstructured":"Sowa-Staszczak, A. et al. Glucagon-like peptide-1 receptor imaging with [Lys40(Ahx-HYNIC- 99mTc\/EDDA)NH2]-exendin-4 for the detection of insulinoma. European journal of nuclear medicine and molecular imaging. \n                           40, 524\u2013531 (2013).","journal-title":"European journal of nuclear medicine and molecular imaging."},{"key":"1852_CR15","doi-asserted-by":"publisher","first-page":"766","DOI":"10.1056\/NEJMc0802045","volume":"359","author":"D Wild","year":"2008","unstructured":"Wild, D. et al. Glucagon-like peptide 1-receptor scans to localize occult insulinomas. The New England journal of medicine. \n                           359, 766\u2013768 (2008).","journal-title":"The New England journal of medicine."},{"key":"1852_CR16","doi-asserted-by":"publisher","first-page":"1075","DOI":"10.2967\/jnumed.115.157768","volume":"56","author":"K Antwi","year":"2015","unstructured":"Antwi, K. et al. Localization of Hidden Insulinomas with (6)(8)Ga-DOTA-Exendin-4 PET\/CT: A Pilot Study. Journal of nuclear medicine: official publication, Society of Nuclear Medicine. \n                           56, 1075\u20131078 (2015).","journal-title":"Journal of nuclear medicine: official publication, Society of Nuclear Medicine."},{"key":"1852_CR17","doi-asserted-by":"publisher","first-page":"1519","DOI":"10.1210\/jc.2013-3541","volume":"99","author":"O Eriksson","year":"2014","unstructured":"Eriksson, O. et al. Detection of metastatic insulinoma by positron emission tomography with [(68)ga]exendin-4-a case report. The Journal of clinical endocrinology and metabolism. \n                           99, 1519\u20131524 (2014).","journal-title":"The Journal of clinical endocrinology and metabolism."},{"key":"1852_CR18","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1016\/j.ecl.2010.09.003","volume":"39","author":"E Christ","year":"2010","unstructured":"Christ, E., Wild, D. & Reubi, J. C. Glucagonlike peptide-1 receptor: an example of translational research in insulinomas: a review. Endocrinology and metabolism clinics of North America. \n                           39, 791\u2013800 (2010).","journal-title":"Endocrinology and metabolism clinics of North America."},{"key":"1852_CR19","doi-asserted-by":"publisher","first-page":"1073","DOI":"10.2967\/jnumed.110.085142","volume":"52","author":"D Wild","year":"2011","unstructured":"Wild, D. et al. Glucagon-like peptide-1 versus somatostatin receptor targeting reveals 2 distinct forms of malignant insulinomas. Journal of nuclear medicine: official publication, Society of Nuclear Medicine. \n                           52, 1073\u20131078 (2011).","journal-title":"Journal of nuclear medicine: official publication, Society of Nuclear Medicine."},{"key":"1852_CR20","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1111\/j.1749-6632.1996.tb17472.x","volume":"805","author":"N Inagaki","year":"1996","unstructured":"Inagaki, N., Kuromi, H. & Seino, S. PACAP\/VIP receptors in pancreatic beta-cells: their roles in insulin secretion. Annals of the New York Academy of Sciences. \n                           805, 44\u201351 (1996). discussion 52\u201343.","journal-title":"Annals of the New York Academy of Sciences."},{"key":"1852_CR21","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1097\/MED.0000000000000218","volume":"23","author":"TW Moody","year":"2016","unstructured":"Moody, T. W., Nuche-Berenguer, B. & Jensen, R. T. Vasoactive intestinal peptide\/pituitary adenylate cyclase activating polypeptide, and their receptors and cancer. Current opinion in endocrinology, diabetes, and obesity. \n                           23, 38\u201347 (2016).","journal-title":"Current opinion in endocrinology, diabetes, and obesity."},{"key":"1852_CR22","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1016\/S0006-8993(00)03126-7","volume":"889","author":"I Tatsuno","year":"2001","unstructured":"Tatsuno, I. et al. Maxadilan specifically interacts with PAC1 receptor, which is a dominant form of PACAP\/VIP family receptors in cultured rat cortical neurons. Brain research. \n                           889, 138\u2013148 (2001).","journal-title":"Brain research."},{"key":"1852_CR23","doi-asserted-by":"publisher","first-page":"5530","DOI":"10.1210\/endo.140.12.7208","volume":"140","author":"P Borboni","year":"1999","unstructured":"Borboni, P. et al. Molecular and functional characterization of pituitary adenylate cyclase-activating polypeptide (PACAP-38)\/vasoactive intestinal polypeptide receptors in pancreatic beta-cells and effects of PACAP-38 on components of the insulin secretory system. Endocrinology. \n                           140, 5530\u20135537 (1999).","journal-title":"Endocrinology."},{"key":"1852_CR24","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1196\/annals.1418.003","volume":"1144","author":"B Ahren","year":"2008","unstructured":"Ahren, B. Role of pituitary adenylate cyclase-activating polypeptide in the pancreatic endocrine system. Annals of the New York Academy of Sciences. \n                           1144, 28\u201335 (2008).","journal-title":"Annals of the New York Academy of Sciences."},{"key":"1852_CR25","first-page":"287","volume":"37","author":"A Arimura","year":"1992","unstructured":"Arimura, A. Pituitary adenylate cyclase activating polypeptide (PACAP): discovery and current status of research. Regulatory peptides. \n                           37, 287\u2013303 (1992).","journal-title":"Regulatory peptides."},{"key":"1852_CR26","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1006\/frne.1995.1003","volume":"16","author":"A Arimura","year":"1995","unstructured":"Arimura, A. & Shioda, S. Pituitary adenylate cyclase activating polypeptide (PACAP) and its receptors: neuroendocrine and endocrine interaction. Frontiers in neuroendocrinology. \n                           16, 53\u201388 (1995).","journal-title":"Frontiers in neuroendocrinology."},{"key":"1852_CR27","doi-asserted-by":"crossref","first-page":"11234","DOI":"10.1016\/S0021-9258(18)99153-2","volume":"266","author":"EA Lerner","year":"1991","unstructured":"Lerner, E. A., Ribeiro, J. M., Nelson, R. J. & Lerner, M. R. Isolation of maxadilan, a potent vasodilatory peptide from the salivary glands of the sand fly Lutzomyia longipalpis. The Journal of biological chemistry. \n                           266, 11234\u201311236 (1991).","journal-title":"The Journal of biological chemistry."},{"key":"1852_CR28","doi-asserted-by":"publisher","first-page":"966","DOI":"10.1074\/jbc.272.2.966","volume":"272","author":"O Moro","year":"1997","unstructured":"Moro, O. & Lerner, E. A. Maxadilan, the vasodilator from sand flies, is a specific pituitary adenylate cyclase activating peptide type I receptor agonist. The Journal of biological chemistry. \n                           272, 966\u2013970 (1997).","journal-title":"The Journal of biological chemistry."},{"key":"1852_CR29","doi-asserted-by":"publisher","first-page":"1651","DOI":"10.1016\/j.peptides.2007.06.021","volume":"28","author":"EA Lerner","year":"2007","unstructured":"Lerner, E. A., Iuga, A. O. & Reddy, V. B. Maxadilan, a PAC1 receptor agonist from sand flies. Peptides. \n                           28, 1651\u20131654 (2007).","journal-title":"Peptides."},{"key":"1852_CR30","doi-asserted-by":"publisher","first-page":"23103","DOI":"10.1074\/jbc.274.33.23103","volume":"274","author":"O Moro","year":"1999","unstructured":"Moro, O. et al. Functional characterization of structural alterations in the sequence of the vasodilatory peptide maxadilan yields a pituitary adenylate cyclase-activating peptide type 1 receptor-specific antagonist. The Journal of biological chemistry. \n                           274, 23103\u201323110 (1999).","journal-title":"The Journal of biological chemistry."},{"key":"1852_CR31","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1007\/s12031-014-0349-9","volume":"54","author":"Z Vamos","year":"2014","unstructured":"Vamos, Z. et al. Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) Induces Relaxations of Peripheral and Cerebral Arteries, which are Differentially Impaired by Aging. Journal of molecular neuroscience: MN. \n                           54, 535\u2013542 (2014).","journal-title":"Journal of molecular neuroscience: MN."},{"key":"1852_CR32","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1016\/S0021-9258(17)42256-3","volume":"269","author":"T Yada","year":"1994","unstructured":"Yada, T. et al. Pituitary adenylate cyclase activating polypeptide is an extraordinarily potent intra-pancreatic regulator of insulin secretion from islet beta-cells. The Journal of biological chemistry. \n                           269, 1290\u20131293 (1994).","journal-title":"The Journal of biological chemistry."},{"key":"1852_CR33","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1007\/s00259-011-1980-0","volume":"39","author":"DO Kiesewetter","year":"2012","unstructured":"Kiesewetter, D. O. et al. 18F-radiolabeled analogs of exendin-4 for PET imaging of GLP-1 in insulinoma. European journal of nuclear medicine and molecular imaging. \n                           39, 463\u2013473 (2012).","journal-title":"European journal of nuclear medicine and molecular imaging."},{"key":"1852_CR34","doi-asserted-by":"publisher","first-page":"1282","DOI":"10.2967\/jnumed.115.168948","volume":"57","author":"SN Rylova","year":"2016","unstructured":"Rylova, S. N. et al. Approaches to Improve the Pharmacokinetics of Radiolabeled Glucagon-Like Peptide-1 Receptor Ligands Using Antagonistic Tracers. Journal of nuclear medicine: official publication, Society of Nuclear Medicine. \n                           57, 1282\u20131288 (2016).","journal-title":"Journal of nuclear medicine: official publication, Society of Nuclear Medicine."},{"key":"1852_CR35","doi-asserted-by":"crossref","unstructured":"Prasad, V. et al. Role of Ga somatostatin receptor PET\/CT in the detection of endogenous hyperinsulinaemic focus: an explorative study. European journal of nuclear medicine and molecular imaging (2016).","DOI":"10.1007\/s00259-016-3331-7"},{"key":"1852_CR36","doi-asserted-by":"publisher","first-page":"613","DOI":"10.2967\/jnumed.114.153189","volume":"56","author":"JC Reubi","year":"2015","unstructured":"Reubi, J. C. & Waser, B. Triple-peptide receptor targeting in vitro allows detection of all tested gut and bronchial NETs. Journal of nuclear medicine: official publication, Society of Nuclear Medicine. \n                           56, 613\u2013615 (2015).","journal-title":"Journal of nuclear medicine: official publication, Society of Nuclear Medicine."},{"key":"1852_CR37","doi-asserted-by":"publisher","first-page":"R1","DOI":"10.1530\/EJE-14-0488","volume":"172","author":"WA van der Zwan","year":"2015","unstructured":"van der Zwan, W. A. et al. GEPNETs update: Radionuclide therapy in neuroendocrine tumors. European journal of endocrinology\/European Federation of Endocrine Societies. \n                           172, R1\u20138 (2015).","journal-title":"European journal of endocrinology\/European Federation of Endocrine Societies."},{"key":"1852_CR38","doi-asserted-by":"publisher","first-page":"1383","DOI":"10.1172\/JCI7537","volume":"104","author":"N Zeng","year":"1999","unstructured":"Zeng, N. et al. PACAP type I receptor activation regulates ECL cells and gastric acid secretion. The Journal of clinical investigation. \n                           104, 1383\u20131391 (1999).","journal-title":"The Journal of clinical investigation."},{"key":"1852_CR39","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1111\/j.1749-6632.1998.tb11173.x","volume":"865","author":"N Zeng","year":"1998","unstructured":"Zeng, N. et al. The pituitary adenylate cyclase activating polypeptide type 1 receptor (PAC1-R) is expressed on gastric ECL cells: evidence by immunocytochemistry and RT-PCR. Annals of the New York Academy of Sciences. \n                           865, 147\u2013156 (1998).","journal-title":"Annals of the New York Academy of Sciences."},{"issue":"Suppl 1","key":"1852_CR40","doi-asserted-by":"publisher","first-page":"S225","DOI":"10.1016\/j.ijsu.2014.05.017","volume":"12","author":"A Cavallaro","year":"2014","unstructured":"Cavallaro, A. et al. The role of 68-Ga-DOTATOC CT-PET in surgical tactic for gastric neuroendocrine tumors treatment: our experience: a case report. International journal of surgery. \n                           12(Suppl 1), S225\u2013231 (2014).","journal-title":"International journal of surgery."},{"key":"1852_CR41","doi-asserted-by":"publisher","first-page":"A604","DOI":"10.1055\/s-0032-1315527","volume":"66","author":"N Kalmbach","year":"2012","unstructured":"Kalmbach, N. et al. Molecular and functional characterization of PACAP\/VIP receptors in Lewis lung carcinoma cells. Pneumologie. \n                           66, A604 (2012).","journal-title":"Pneumologie."},{"key":"1852_CR42","first-page":"3105","volume":"60","author":"JC Reubi","year":"2000","unstructured":"Reubi, J. C. et al. Vasoactive intestinal peptide\/pituitary adenylate cyclase-activating peptide receptor subtypes in human tumors and their tissues of origin. Cancer research. \n                           60, 3105\u20133112 (2000).","journal-title":"Cancer research."},{"key":"1852_CR43","first-page":"1235","volume":"77","author":"P Robberecht","year":"1993","unstructured":"Robberecht, P. et al. Receptors for pituitary adenylate cyclase activating peptides in human pituitary adenomas. The Journal of clinical endocrinology and metabolism. \n                           77, 1235\u20131239 (1993).","journal-title":"The Journal of clinical endocrinology and metabolism."},{"key":"1852_CR44","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1016\/0196-9781(94)90092-2","volume":"15","author":"P Robberecht","year":"1994","unstructured":"Robberecht, P. et al. Expression of pituitary adenylate cyclase activating polypeptide (PACAP) receptors in human glial cell tumors. Peptides. \n                           15, 661\u2013665 (1994).","journal-title":"Peptides."},{"key":"1852_CR45","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1002\/(SICI)1097-4652(199604)167:1<36::AID-JCP4>3.0.CO;2-D","volume":"167","author":"P Vertongen","year":"1996","unstructured":"Vertongen, P. et al. Pituitary adenylate cyclase activating peptide and its receptors are expressed in human neuroblastomas. Journal of cellular physiology. \n                           167, 36\u201346 (1996).","journal-title":"Journal of cellular physiology."},{"key":"1852_CR46","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1016\/S0196-9781(03)00058-5","volume":"24","author":"R Busto","year":"2003","unstructured":"Busto, R. et al. VIP and PACAP receptors coupled to adenylyl cyclase in human lung cancer: a study in biopsy specimens. Peptides. \n                           24, 429\u2013436 (2003).","journal-title":"Peptides."},{"key":"1852_CR47","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1210\/endo.130.1.1370150","volume":"130","author":"M Asfari","year":"1992","unstructured":"Asfari, M. et al. Establishment of 2-mercaptoethanol-dependent differentiated insulin-secreting cell lines. Endocrinology. \n                           130, 167\u2013178 (1992).","journal-title":"Endocrinology."},{"key":"1852_CR48","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1002\/cmmi.475","volume":"7","author":"M Brom","year":"2012","unstructured":"Brom, M. et al. Radiolabelled GLP-1 analogues for in vivo targeting of insulinomas. Contrast media & molecular imaging. \n                           7, 160\u2013166 (2012).","journal-title":"Contrast media & molecular imaging."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-01852-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-01852-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-01852-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T04:07:42Z","timestamp":1671768462000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-01852-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,5,11]]},"references-count":48,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,12]]}},"alternative-id":["1852"],"URL":"https:\/\/doi.org\/10.1038\/s41598-017-01852-8","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,5,11]]},"assertion":[{"value":"26 August 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 April 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 May 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"1751"}}