{"doi":"10.1002/jlcr.3831","title":"Development of an automated, GMP compliant FASTlab™ radiosynthesis of [<sup>18</sup>F]GE‐179 for the clinical study of activated NMDA receptors","abstract":"<jats:title>Abstract</jats:title><jats:p><jats:italic>N</jats:italic>‐(2‐chloro‐5‐(<jats:italic>S</jats:italic>‐2‐[<jats:sup>18</jats:sup>F]fluoroethyl)thiophenyl)‐<jats:italic>N</jats:italic>'‐(3‐thiomethylphenyl)‐<jats:italic>N</jats:italic>'‐methylguanidine, ([<jats:sup>18</jats:sup>F]<jats:bold>GE‐179</jats:bold>), has been identified as a promising positron emission tomography (PET) ligand for the intra‐channel phencyclidine (PCP) binding site of the <jats:italic>N</jats:italic>‐methyl‐<jats:italic>D</jats:italic>‐aspartate (NMDA) receptor. The radiosynthesis of [<jats:sup>18</jats:sup>F]<jats:bold>GE‐179</jats:bold> has only been performed at low radioactivity levels. However, the manufacture of a GMP compliant product at high radioactivity levels was required for clinical studies. We describe the development of a process using the GE FASTlab™ radiosynthesis platform coupled with HPLC purification. The radiosynthesis is a two‐step process, involving the nucleophilic fluorination of ethylene ditosylate, <jats:bold>11</jats:bold>, followed by alkylation to the deprotonated thiol precursor, <jats:italic>N</jats:italic>‐(2‐chloro‐5‐thiophenol)‐<jats:italic>N</jats:italic>'‐(3‐thiomethylphenyl)‐<jats:italic>N</jats:italic>'‐methyl guanidine, <jats:bold>8</jats:bold>. The crude product was purified by semi‐preparative HPLC to give the formulated product in an activity yield (AY) of 7 ± 2% (<jats:italic>n</jats:italic> = 15) with a total synthesis time of 120 minutes. The radioactive concentration (RAC) and radiochemical purity (RCP) were 328 ± 77 MBq/mL and 96.5 ± 1% respectively and the total chemical content was 2 ± 1 μg. The final formulation volume was 14 mL. The previously described radiosynthesis of [<jats:sup>18</jats:sup>F]<jats:bold>GE‐179</jats:bold> was successfully modified to deliver an process on the FASTlab™ that allows the manufacture of a GMP quality product from high starting radioactivitity (up to 80 GBq) and delivers a product suitable for clinical use.</jats:p>","journal":"Journal of Labelled Compounds and Radiopharmaceuticals","year":2020,"id":649380,"datarank":0.26876392038420827,"base_score":1.791759469228055,"endowment":1.791759469228055,"self_citation_contribution":0.26876392038420827,"citation_network_contribution":0.0,"self_endowment_contribution":0.26876392038420827,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"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":1692799,"name":"Tom Christian Berg","orcid":null,"position":1,"is_corresponding":false},{"id":1692800,"name":"Jane Brown","orcid":null,"position":2,"is_corresponding":false},{"id":1692801,"name":"Rajiv Bhalla","orcid":null,"position":3,"is_corresponding":false},{"id":1692802,"name":"Anthony Wilson","orcid":null,"position":4,"is_corresponding":false},{"id":151429,"name":"Andrew Black","orcid":null,"position":5,"is_corresponding":false},{"id":1692803,"name":"Graeme McRobbie","orcid":null,"position":6,"is_corresponding":false},{"id":1692804,"name":"James Nairne","orcid":null,"position":7,"is_corresponding":false},{"id":864750,"name":"Andreas Olsson","orcid":"0000-0001-5272-7744","position":8,"is_corresponding":false},{"id":1692805,"name":"William Trigg","orcid":null,"position":9,"is_corresponding":false},{"id":1666649,"name":"Imtiaz Khan","orcid":"0000-0002-7088-8215","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Development of an automated, GMP compliant FASTlab™ radiosynthesis of [<sup>18</sup>F]GE‐179 for the clinical study of activated NMDA receptors","abstract":"<jats:title>Abstract</jats:title><jats:p><jats:italic>N</jats:italic>‐(2‐chloro‐5‐(<jats:italic>S</jats:italic>‐2‐[<jats:sup>18</jats:sup>F]fluoroethyl)thiophenyl)‐<jats:italic>N</jats:italic>'‐(3‐thiomethylphenyl)‐<jats:italic>N</jats:italic>'‐methylguanidine, ([<jats:sup>18</jats:sup>F]<jats:bold>GE‐179</jats:bold>), has been identified as a promising positron emission tomography (PET) ligand for the intra‐channel phencyclidine (PCP) binding site of the <jats:italic>N</jats:italic>‐methyl‐<jats:italic>D</jats:italic>‐aspartate (NMDA) receptor. The radiosynthesis of [<jats:sup>18</jats:sup>F]<jats:bold>GE‐179</jats:bold> has only been performed at low radioactivity levels. However, the manufacture of a GMP compliant product at high radioactivity levels was required for clinical studies. We describe the development of a process using the GE FASTlab™ radiosynthesis platform coupled with HPLC purification. The radiosynthesis is a two‐step process, involving the nucleophilic fluorination of ethylene ditosylate, <jats:bold>11</jats:bold>, followed by alkylation to the deprotonated thiol precursor, <jats:italic>N</jats:italic>‐(2‐chloro‐5‐thiophenol)‐<jats:italic>N</jats:italic>'‐(3‐thiomethylphenyl)‐<jats:italic>N</jats:italic>'‐methyl guanidine, <jats:bold>8</jats:bold>. The crude product was purified by semi‐preparative HPLC to give the formulated product in an activity yield (AY) of 7 ± 2% (<jats:italic>n</jats:italic> = 15) with a total synthesis time of 120 minutes. The radioactive concentration (RAC) and radiochemical purity (RCP) were 328 ± 77 MBq/mL and 96.5 ± 1% respectively and the total chemical content was 2 ± 1 μg. The final formulation volume was 14 mL. The previously described radiosynthesis of [<jats:sup>18</jats:sup>F]<jats:bold>GE‐179</jats:bold> was successfully modified to deliver an process on the FASTlab™ that allows the manufacture of a GMP quality product from high starting radioactivitity (up to 80 GBq) and delivers a product suitable for clinical use.</jats:p>","is_dataset_classified":null,"base_score":1.791759469228055,"endowment":1.791759469228055,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"31986223","pmcid":null,"openalex_id":"https://openalex.org/W3000778148","authors":[],"funders":[],"total_grants":0,"fwci":0.3097,"citation_percentile":0.58340511,"influential_citations":0,"citation_trend":[{"year":2021,"count":1},{"year":2022,"count":2},{"year":2024,"count":1},{"year":2026,"count":1}],"oa_status":"closed","license":"http://onlinelibrary.wiley.com/termsAndConditions#vor","oa_locations":[{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fjlcr.3831","host_type":"publisher"},{"url":"https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/pdf/10.1002/jlcr.3831","host_type":"publisher"},{"url":"https://doi.org/10.1002/jlcr.3831","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/31986223","host_type":"repository"}],"fields_of_study":["Medical Imaging Techniques and Applications","Chemical Reactions and Isotopes","Radiopharmaceutical Chemistry and Applications"],"mesh_terms":["Automation","Fluorine Radioisotopes","Guanidines","Humans","Radiochemistry","Receptors, N-Methyl-D-Aspartate","Radiopharmaceuticals","Chemistry Techniques, Synthetic"],"keywords":["Radiosynthesis","Chemistry","Guanidine","Ligand (biochemistry)","Radiochemistry","Yield (engineering)","High-performance liquid chromatography","Nuclear chemistry","Chromatography","Receptor","Organic chemistry","Positron emission tomography","Nuclear medicine","Biochemistry","Alkylation","PET","automation","Ge-179","2-[18F]fluoroethyl Tosylate","Fastlabtm, N-methyl-d-aspartate (Nmda) Receptor, Gmp."],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-10T03:37:16.552176Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}