{"doi":"10.1101/2022.11.12.516260","title":"High-Contrast PET imaging with [ <sup>18</sup> F]-NT160, a Class-IIa Histone Deacetylase (Class-IIa HDAC) Probe for In Vivo Imaging of Epigenetic Machinery in the Central Nervous System","abstract":"Abstract We utilized positron emission tomography (PET) imaging in vivo to map the spatiotemporal biodistribution/expression (protein density) of class-IIa histone deacetylases (class-IIa HDACs) in the brain. Herein, we report an improved radiosynthesis of [ 18 F]-NT160 using 4-hydroxy-TEMPO which led to a significant improvement in radiochemical yield and molar activity. PET imaging with [ 18 F]-NT160, a highly potent class-IIa HDAC inhibitor with sub-nM affinity for HDAC4 and 5 isoforms, led to high-quality and high-contrast images among various brain regions. [ 18 F]-NT160 displayed excellent pharmacokinetic and imaging characteristics: brain uptake is high in gray matter regions, leading to high-quality PET images; tissue kinetics are appropriate for an 18 F tracer and specific binding for class-IIa HDACs is demonstrated by self-blockade. Higher uptake with [ 18 F]-NT160 was observed in the hippocampus, thalamus, and cortex while there was relatively lower uptake in the cerebellum and striatum. Overall, our current studies with [ 18 F]-NT160 will likely facilitate the development and clinical translation of class-IIa HDACs of the next generation of PET tracers for imaging and targeted therapy of cancer and the diseases of the central nervous system (CNS).","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":313078,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9594,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1011350,"name":"Sulan Xu","orcid":null,"position":1,"is_corresponding":false},{"id":1010904,"name":"Chun-Han Huang","orcid":"0009-0005-3143-6936","position":2,"is_corresponding":false},{"id":773284,"name":"Christopher Eyermann","orcid":null,"position":3,"is_corresponding":false},{"id":1011351,"name":"Julia Salino","orcid":null,"position":4,"is_corresponding":false},{"id":584676,"name":"Palwasha Khan","orcid":"0000-0002-0873-8355","position":5,"is_corresponding":false},{"id":750030,"name":"Nashaat Turkman","orcid":"0000-0002-7943-6637","position":0,"is_corresponding":true}],"reference_count":40,"raw_metadata":null,"created_at":"2026-07-19T00:33:40.460845Z","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":[]}