{"doi":"10.1101/2021.06.25.449978","title":"A metabolically stable PET tracer for imaging synaptic vesicle protein 2A: Synthesis and preclinical characterization of [ <sup>18</sup> F]SDM-16","abstract":"ABSTRACT Purpose To investigate the synaptic vesicle glycoprotein 2A (SV2A) expression in the whole central nervous system and peripheral tissues, a metabolically stable SV2A radiotracer is desirable to minimize a potential confounding effect of radiometabolites. The aim of this study was to develop and evaluate a metabolically stable SV2A radiotracer, [ 18 F]SDM-16, in nonhuman primate brains. Methods The racemic SDM-16 (4-(3,5-difluorophenyl)-1-((2-methyl-1H-imidazol-1-yl)methyl)pyrrolidin-2-one) was synthesized and assayed for in vitro SV2A binding affinity. We synthesized the enantiopure [ 18 F]SDM-16 using the corresponding arylstannane precursor. Nonhuman primate brain PET was performed on a FOCUS 220 system. Arterial blood was drawn for metabolite analysis and construction of plasma input function. Regional time-activity curves (TACs) were evaluated with the one-tissue compartment (1TC) model to obtain the volume of distribution ( V T ). Binding potential ( BP ND ) was calculated using either the nondisplaceable volume of distribution ( V ND ) or the centrum semiovale (CS) as the reference region. Results Racemic SDM-16 was synthesized in 3 steps with 44% overall yield and has high affinity ( K i = 3.7 nM) to human SV2A. [ 18 F]SDM-16 was prepared in greater than 99% radiochemical and enantiomeric purity. This radiotracer displayed high specific binding in brain and was metabolically more stable than other SV2A PET tracers. The plasma free fraction ( f P ) of [ 18 F]SDM-16 was 69%, which was higher than those of [ 11 C]UCB-J (46%), [ 18 F]SynVesT-1 (43%), [ 18 F]SynVesT-2 (41%), and [ 18 F]UCB-H (43%). The TACs were well described with the 1TC. The averaged test-retest variability (TRV) was −9±8%, and averaged absolute TRV (aTRV) was 10±7% for all analyzed brain regions. Conclusion We have successfully synthesized a metabolically stable and high affinity SV2A PET tracer, [ 18 F]SDM-16, which showed high specific and reversible binding in the NHP brain. [ 18 F]SDM-16 may have potential application in the visualization and quantification of SV2A beyond the brain.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":222002,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9551,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":822586,"name":"Daniel Holden","orcid":"0000-0001-7585-4463","position":1,"is_corresponding":false},{"id":673370,"name":"Ming‐Qiang Zheng","orcid":null,"position":2,"is_corresponding":false},{"id":823155,"name":"Richard Pracitto","orcid":null,"position":3,"is_corresponding":false},{"id":454006,"name":"Kyle C. Wilcox","orcid":null,"position":4,"is_corresponding":false},{"id":822632,"name":"Marcel Lindemann","orcid":"0000-0002-5883-8004","position":5,"is_corresponding":false},{"id":823127,"name":"Zachary Felchner","orcid":null,"position":6,"is_corresponding":false},{"id":3069,"name":"Li Zhang","orcid":"0000-0002-3617-2627","position":7,"is_corresponding":false},{"id":290728,"name":"Jie Tong","orcid":"0000-0002-7138-0886","position":8,"is_corresponding":false},{"id":823156,"name":"Krista Fowles","orcid":null,"position":9,"is_corresponding":false},{"id":786647,"name":"Sjoerd J. Finnema","orcid":"0000-0002-4972-3627","position":10,"is_corresponding":false},{"id":235258,"name":"Nabeel Nabulsi","orcid":"0000-0001-8129-0051","position":11,"is_corresponding":false},{"id":235261,"name":"Richard E. Carson","orcid":"0000-0002-9338-7966","position":12,"is_corresponding":false},{"id":235260,"name":"Yiyun Huang","orcid":"0000-0002-6757-3220","position":13,"is_corresponding":false},{"id":305956,"name":"Zhengxin Cai","orcid":"0000-0002-2005-6760","position":14,"is_corresponding":false},{"id":270757,"name":"Chao Zheng","orcid":"0000-0002-2179-8096","position":0,"is_corresponding":true}],"reference_count":54,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:53:59.302331Z","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":[]}