{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T05:52:04Z","timestamp":1777614724564,"version":"3.51.4"},"reference-count":19,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,6,12]],"date-time":"2020-06-12T00:00:00Z","timestamp":1591920000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,6,12]],"date-time":"2020-06-12T00:00:00Z","timestamp":1591920000000},"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":["EJNMMI Res"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>4-[<jats:sup>18<\/jats:sup>F] fluorobenzyl dexetimide (F-DEX) is the first non-subtype selective fluorine-18 labelled tracer for muscarinic receptors (mAChR) used in humans. A recent first-in-human study found high regional brain uptake with low variation in normal subjects. Disturbance of mAChR has been reported in Alzheimer\u2019s and Parkinson\u2019s disease, schizophrenia and depression and various cardiac diseases. The following work assesses the biodistribution, organ tracer kinetics and radiation dose associated with F-DEX.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Method<\/jats:title>\n                <jats:p>Dose calculations were based on activity uptake derived from multiple time point whole body PET CT imaging and the organ-specific dosimetric S-factors derived from the ICRP 133 standard man and woman mathematical phantoms. Effective doses were calculated using the latest ICRP tissue weighting factors.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Serial images and time activity curves demonstrate high brain and left ventricular myocardial uptake (5% and 0.65<jats:italic>%<\/jats:italic> of injected activity, respectively) with greater retention in brain than myocardium. The mean effective dose was in concordance with other <jats:sup>18<\/jats:sup><jats:italic>F<\/jats:italic> labelled tracers at 19.70 \u00b1 2.27 \u03bcSv\/MBq. The largest absorbed doses were in the liver (52.91 \u00b1 1.46 \u03bcGy\/MBq) and heart wall (43.94 \u00b1 12.88 \u03bcGy\/MBq) for standard man and the liver (61.66 \u00b1 13.61 \u03bcGy\/MBq) and lungs (40.93 \u00b1 3.11 \u03bcGy\/MBq) for standard woman. The absorbed dose to all organs, most notably, the red bone marrow (20.03 \u00b1 2.89 \u03bcGy\/MBq) was sufficiently low to ensure no toxicity after numerous follow-up procedures.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>The radiation dose associated with an administration of F-DEX is comparable to that of other <jats:sup>18<\/jats:sup><jats:italic>F<\/jats:italic> labelled tracers such as FDG (19.0 \u03bcSv\/MBq) and lower than tracers used for SPECT imaging of muscarinic receptors (I-DEX 28.5 \u03bcSv\/MBq). Clinical use would likely result in an effective dose less than 4 <jats:italic>m<\/jats:italic><jats:italic>S<\/jats:italic><jats:italic>v<\/jats:italic> for the ICRP 133 standard phantoms after dose optimisation allowing justification for numerous follow-up procedures. Recent results from first in-human studies and a comparatively low radiation dose make F-DEX an attractive option for future applications of imaging muscarinic receptors in the brain. Further investigation of the potential of F-DEX for imaging parasympathetic innervation of the heart may be warranted.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13550-020-00641-1","type":"journal-article","created":{"date-parts":[[2020,6,12]],"date-time":"2020-06-12T10:03:45Z","timestamp":1591956225000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Human biodistribution and internal dosimetry of 4-[ 18F]fluorobenzyl-dexetimide: a PET radiopharmaceutical for imaging muscarinic acetylcholine receptors in the brain and heart"],"prefix":"10.1186","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6294-036X","authenticated-orcid":false,"given":"Cameron D.","family":"Pain","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Graeme J.","family":"O\u2019Keefe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Uwe","family":"Ackermann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincent","family":"Dore","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victor L.","family":"Villemagne","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher C.","family":"Rowe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,6,12]]},"reference":[{"issue":"supplement 1","key":"641_CR1","first-page":"1470","volume":"60","author":"C Rowe","year":"2019","unstructured":"Rowe C, Dean B, Ackermann U, Goh R, Guzman R, Kanaan R, Chong L, Dore V, Bozinovski S, Masters C, et al.In vivo imaging of brain muscarinic receptors with 18f-flurobenzyl dexetimide: first in human studies. J Nucl Med. 2019; 60(supplement 1):1470.","journal-title":"J Nucl Med"},{"issue":"5","key":"641_CR2","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1002\/ana.410320505","volume":"32","author":"DST DeKosky","year":"1992","unstructured":"DeKosky DST, Harbaugh RE, Schmitt FA, Bakay RA, Chui HC, Knopman DS, Reeder TM, Shetter AG, Senter HJ, Markesbery WR, et al.Cortical biopsy in alzheimer\u2019s disease: diagnostic accuracy and neurochemical, neuropathological, and cognitive correlations. Ann Neurol. 1992; 32(5):625\u201332.","journal-title":"Ann Neurol"},{"key":"641_CR3","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1016\/j.nicl.2018.02.030","volume":"18","author":"G Bakker","year":"2018","unstructured":"Bakker G, Vingerhoets C, Boucherie D, Caan M, Bloemen O, Eersels J, Booij J, van Amelsvoort T. Relationship between muscarinic m1 receptor binding and cognition in medication-free subjects with psychosis. NeuroImage Clin. 2018; 18:713\u20139.","journal-title":"NeuroImage Clin"},{"issue":"4","key":"641_CR4","doi-asserted-by":"publisher","first-page":"562","DOI":"10.1038\/jcbfm.1992.80","volume":"12","author":"HW M\u00fcller-G\u00e4rtner","year":"1992","unstructured":"M\u00fcller-G\u00e4rtner HW, Wilson AA, Dannals RF, Wagner Jr HN, Frost JJ. Imaging muscarinic cholinergic receptors in human brain in vivo with SPECT [123i] 4-iododexetimide, and [123i] 4-iodolevetimide. J Cereb Blood Flow Metab. 1992; 12(4):562\u201370.","journal-title":"J Cereb Blood Flow Metab"},{"issue":"1","key":"641_CR5","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1007\/s002130000679","volume":"156","author":"J Lavalaye","year":"2001","unstructured":"Lavalaye J, Booij J, Linszen D, Reneman L, Van Royen E. Higher occupancy of muscarinic receptors by olanzapine than risperidone in patients with schizophrenia. Psychopharmacology. 2001; 156(1):53\u20137.","journal-title":"Psychopharmacology"},{"issue":"11","key":"641_CR6","doi-asserted-by":"publisher","first-page":"1229","DOI":"10.1002\/jlcr.2580201103","volume":"20","author":"MM Vora","year":"1983","unstructured":"Vora MM, Finn RD, Boothe TE, Liskwosky DR, Potter LT. [n-methyl-11c]-scopolamine: synthesis and distribution in rat brain. J Label Compd Radiopharm. 1983; 20(11):1229\u201336.","journal-title":"J Label Compd Radiopharm"},{"issue":"1","key":"641_CR7","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1186\/2191-219X-3-19","volume":"3","author":"HJ Buiter","year":"2013","unstructured":"Buiter HJ, Windhorst AD, Huisman MC, Yaqub M, Knol DL, Fisher A, Lammertsma AA, Leysen JE. [11 c] af150 (s), an agonist pet ligand for m1 muscarinic acetylcholine receptors. EJNMMI Res. 2013; 3(1):19.","journal-title":"EJNMMI Res"},{"issue":"1","key":"641_CR8","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/0969-8051(94)00082-U","volume":"22","author":"GK Mulholland","year":"1995","unstructured":"Mulholland GK, Kilbourn MR, Sherman P, Carey JE, Frey KA, Koeppe RA, Kuhl DE. Synthesis, in vivo biodistribution and dosimetry of [11c] n-methylpiperidyl benzilate ([11c] nmpb), a muscarinic acetylcholine receptor antagonist. Nucl Med Biol. 1995; 22(1):13\u20137.","journal-title":"Nucl Med Biol"},{"issue":"3","key":"641_CR9","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1002\/syn.890050307","volume":"5","author":"SL Dewey","year":"1990","unstructured":"Dewey SL, Macgregor RR, Brodie JD, Bendriem B, King PT, Volkow ND, Schlyer DJ, Fowler JS, Wolf AP, Gatley SJ, et al.Mapping muscarinic receptors in human and baboon brain using [n-11c-methyl]-benztropine. Synapse. 1990; 5(3):213\u201323.","journal-title":"Synapse"},{"issue":"2","key":"641_CR10","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1016\/0014-2999(92)90692-W","volume":"213","author":"M Varastet","year":"1992","unstructured":"Varastet M, Brouillet E, Chavoix C, Prenant C, Crouzel C, Stulzaft O, Bottlaender M, Cayla J, Mazi\u00e8re B, Mazi\u00e8re M. In vivo visualization of central muscarinic receptors using [11c] quinuclidinyl benzilate and positron emission tomography in baboons. Eur J Pharmacol. 1992; 213(2):275\u201384.","journal-title":"Eur J Pharmacol"},{"issue":"2","key":"641_CR11","first-page":"1","volume":"45","author":"ICRP","year":"2016","unstructured":"ICRP. The ICRP computational framework for internal dose assessment for reference adults: specific absorbed fractions. ICRP Publ 133 Ann ICRP. 2016; 45(2):1\u201374.","journal-title":"ICRP Publ 133 Ann ICRP"},{"key":"641_CR12","unstructured":"ICRP. The 2007 recommendations of the international commission on radiological protection. ICRP Publ 103 Ann ICRP. 2007; 37."},{"issue":"3","key":"641_CR13","doi-asserted-by":"publisher","first-page":"477","DOI":"10.2967\/jnumed.108.056036","volume":"50","author":"WE Bolch","year":"2009","unstructured":"Bolch WE, Eckerman KF, Sgouros G, Thomas SR. Mird pamphlet no. 21: a generalized schema for radiopharmaceutical dosimetry standardization of nomenclature. J Nucl Med. 2009; 50(3):477\u201384.","journal-title":"J Nucl Med"},{"key":"641_CR14","doi-asserted-by":"crossref","unstructured":"ICRP. Radiation dose to patients from radiopharmaceuticals - addendum 3 to ICRP publication 53. ICRP Publ 106 Ann ICRP. 2008; 38.","DOI":"10.1016\/j.icrp.2008.09.002"},{"issue":"2","key":"641_CR15","doi-asserted-by":"publisher","first-page":"309","DOI":"10.2967\/jnumed.108.055756","volume":"50","author":"GJ O\u2019Keefe","year":"2009","unstructured":"O\u2019Keefe GJ, Saunder TH, Ng S, Ackerman U, Tochon-Danguy HJ, Chan JG, Gong S, Dyrks T, Lindemann S, Holl G, et al.Radiation dosimetry of \u03b2-amyloid tracers 11c-pib and 18f-bay94-9172. J Nucl Med. 2009; 50(2):309\u201315.","journal-title":"J Nucl Med"},{"issue":"5","key":"641_CR16","doi-asserted-by":"publisher","first-page":"787","DOI":"10.2967\/jnumed.111.088955","volume":"53","author":"M Doss","year":"2012","unstructured":"Doss M, Kolb HC, Zhang JJ, B\u00e9langer M-J, Stubbs JB, Stabin MG, Hostetler ED, Alpaugh RK, von Mehren M, Walsh JC, et al.Biodistribution and radiation dosimetry of the integrin marker 18f-RGD-k5 determined from whole-body PET\/CT in monkeys and humans. J Nucl Med. 2012; 53(5):787\u201395.","journal-title":"J Nucl Med"},{"issue":"4","key":"641_CR17","first-page":"596","volume":"44","author":"M Bottlaender","year":"2003","unstructured":"Bottlaender M, Valette H, Roumenov D, Doll\u00e9 F, Coulon C, Ottaviani M, Hinnen F, Ricard M. Biodistribution and radiation dosimetry of 18f-fluoro-a-85380 in healthy volunteers. J Nucl Med. 2003; 44(4):596\u2013601.","journal-title":"J Nucl Med"},{"issue":"7","key":"641_CR18","first-page":"1332","volume":"36","author":"KL Boundy","year":"1995","unstructured":"Boundy KL, Barnden LR, Rowe CC, Reid M, Kassiou M, Katsifis AG, Lambrecht RM. Human dosimetry and biodistribution of iodine-123-iododexetimide: a SPECT imaging agent for cholinergic muscarinic neuroreceptors. J Nucl Med. 1995; 36(7):1332\u20138.","journal-title":"J Nucl Med"},{"key":"641_CR19","doi-asserted-by":"crossref","unstructured":"ICRP. ICRP statement on tissue reactions \/ early and late effects of radiation in normal tissues and organs - threshold doses for tissue reactions in a radiation protection context. ICRP Publ 118 Ann ICRP. 2012; 41.","DOI":"10.1016\/j.icrp.2012.02.001"}],"container-title":["EJNMMI Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13550-020-00641-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13550-020-00641-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13550-020-00641-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,6,11]],"date-time":"2021-06-11T23:07:27Z","timestamp":1623452847000},"score":1,"resource":{"primary":{"URL":"https:\/\/ejnmmires.springeropen.com\/articles\/10.1186\/s13550-020-00641-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,12]]},"references-count":19,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["641"],"URL":"https:\/\/doi.org\/10.1186\/s13550-020-00641-1","relation":{},"ISSN":["2191-219X"],"issn-type":[{"value":"2191-219X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,12]]},"assertion":[{"value":"23 March 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 May 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 June 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"This study was approved by the Austin Health Human Research Ethics Committee, and written consent was obtained from all subjects before the imaging studies.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"61"}}