{"doi":"10.3389/fphar.2019.00534","title":"In vitro and in vivo Human Metabolism of (S)-[18F]Fluspidine – A Radioligand for Imaging σ1 Receptors With Positron Emission Tomography (PET)","abstract":null,"journal":"Frontiers in Pharmacology","year":2019,"id":622294,"datarank":0.37273599746820013,"base_score":2.4849066497880004,"endowment":2.4849066497880004,"self_citation_contribution":0.37273599746820013,"citation_network_contribution":0.0,"self_endowment_contribution":0.37273599746820013,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":11,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1227302,"name":"Steffen Fischer","orcid":"0000-0002-9821-2313","position":1,"is_corresponding":false},{"id":1607776,"name":"Richard Houska","orcid":null,"position":2,"is_corresponding":false},{"id":1607777,"name":"Alexander Hoepping","orcid":null,"position":3,"is_corresponding":false},{"id":1607778,"name":"Winnie Deuther-Conrad","orcid":null,"position":4,"is_corresponding":false},{"id":1607779,"name":"Dirk Schepmann","orcid":null,"position":5,"is_corresponding":false},{"id":813071,"name":"Marianne Patt","orcid":"0000-0001-9696-4477","position":6,"is_corresponding":false},{"id":1607780,"name":"Philipp M. Meyer","orcid":null,"position":7,"is_corresponding":false},{"id":1607781,"name":"Swen Hesse","orcid":null,"position":8,"is_corresponding":false},{"id":1607782,"name":"Georg-Alexander Becker","orcid":null,"position":9,"is_corresponding":false},{"id":1607783,"name":"Franziska Ruth Zientek","orcid":null,"position":10,"is_corresponding":false},{"id":1607784,"name":"Jörg Steinbach","orcid":null,"position":11,"is_corresponding":false},{"id":825208,"name":"Bernhard Wünsch","orcid":null,"position":12,"is_corresponding":false},{"id":356666,"name":"Osama Sabri","orcid":"0000-0002-6425-3504","position":13,"is_corresponding":false},{"id":270718,"name":"Peter Brust","orcid":"0000-0001-5555-7058","position":14,"is_corresponding":false},{"id":1607775,"name":"Friedrich-Alexander Ludwig","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"In vitro and in vivo Human Metabolism of (S)-[18F]Fluspidine – A Radioligand for Imaging σ1 Receptors With Positron Emission Tomography (PET)","abstract":"(S)-[18F]fluspidine ((S)-[18F]1) has recently been explored for PET imaging of sigma-1 receptors in humans. In the current report, we have used plasma samples of healthy volunteers to investigate the radiometabolites of (S)-[18F]1 and elucidate their structures with LC-MS/MS. For the latter purpose additional in vitro studies were conducted by incubation of (S)-[18F]1 and (S)-1 with human liver microsomes (HLM). In vitro metabolites were characterized by interpretation of MS/MS fragmentation patterns from collision-induced dissociation or by use of reference compounds. Thereby, structures of corresponding radio-HPLC-detected radiometabolites, both in vitro and in vivo (human), could be identified. By incubation with HLM, mainly debenzylation and hydroxylation occurred, beside further mono- and di-oxygenations. The product hydroxylated at the fluoroethyl side chain was glucuronidated. Plasma samples (10, 20, 30 min p.i., n=5-6), obtained from human subjects receiving 250-300 MBq (S)-[18F]1 showed 97.2%, 95.4%, and 91.0% of unchanged radioligand, respectively. In urine samples (90 min p.i.) the fraction of unchanged radioligand was only 2.6% and three major radiometabolites were detected. The one with the highest percentage, also found in plasma, matched the glucuronide formed in vitro. Only a small amount of debenzylated metabolite was detected. In conclusion, our metabolic study, in particular the high fractions of unchanged radioligand in plasma, confirms the suitability of (S)-[18F]1 as PET radioligand for sigma-1 receptor imaging.","is_dataset_classified":null,"base_score":2.4849066497880004,"endowment":2.4849066497880004,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"31263411","pmcid":"PMC6585474","openalex_id":"https://openalex.org/W2950625227","authors":[],"funders":[{"funder_name":"Fundação para a Ciência e a Tecnologia, I.P.","grant_id":"PTDC/CCI-INF/6762/2020","title":"MS3: New foundations for micro-services and serverless systems"},{"funder_name":"Deutsche Forschungsgemeinschaft","grant_id":"unidentified","title":"unidentified"},{"funder_name":"Deutsche Forschungsgemeinschaft","grant_id":"","title":null}],"total_grants":3,"fwci":0.4552,"citation_percentile":0.60006592,"influential_citations":0,"citation_trend":[{"year":2020,"count":4},{"year":2022,"count":2},{"year":2023,"count":1},{"year":2024,"count":3},{"year":2025,"count":1}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.frontiersin.org/articles/10.3389/fphar.2019.00534/pdf","host_type":"journal"},{"url":"https://www.frontiersin.org/articles/10.3389/fphar.2019.00534/pdf","host_type":"publisher"},{"url":"https://www.frontiersin.org/article/10.3389/fphar.2019.00534/full","host_type":"publisher"},{"url":"https://doi.org/10.3389/fphar.2019.00534","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/31263411","host_type":"repository"},{"url":"https://doaj.org/article/7fa023e5037f427080aa634c67f8af79","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/6585474","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC6585474","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC6585474?pdf=render","host_type":"Europe_PMC"},{"url":"http://dx.doi.org/10.3389/fphar.2019.00534","host_type":""},{"url":"https://dx.doi.org/10.3389/fphar.2019.00534","host_type":""},{"url":"https://www.hzdr.de/publications/Publ-28946-1","host_type":""}],"fields_of_study":["Pharmacological Receptor Mechanisms and Effects","Neuropeptides and Animal Physiology","Receptor Mechanisms and Signaling","0301 basic medicine","0303 health sciences","03 medical and health sciences"],"mesh_terms":[],"keywords":["Radioligand","Positron emission tomography","In vivo","Brain positron emission tomography","Preclinical imaging","Pet imaging","In vitro","Nuclear medicine","Positron","Chemistry","Medicine","Neuroscience","Physics","Biology","Biochemistry","Nuclear physics","Liquid chromatography-mass spectrometry","liver microsomes","Sigma-1 Receptors","Radiometabolites","Fluspidine","Pharmacology","RM1-950","Sigma-1 receptors (S1R)","positron emission tomography (PET)","Therapeutics. 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