{"doi":"10.1101/2025.01.16.633384","title":"Preclinical Evaluation of [ <sup>18</sup> F]P4B-2412 as Phosphodiesterase 4B Radioligand for Positron Emission Tomography Imaging","abstract":"ABSTRACT Phosphodiesterase 4B (PDE4B) plays a critical role in cAMP hydrolysis and is highly expressed in brain regions associated with neuroinflammation and neurodegenerative disorders. Selective PDE4B radioligands hold significant potential for elucidating disease mechanisms and enabling target occupancy measurements. In this study, we developed [ 18 F]P4B-2412, a novel PDE4B-selective radioligand, and evaluated its utility for PET imaging. [ 18 F]P4B-2412 was synthesized with high radiochemical yield (27.2%), excellent radiochemical purity (99%), and favorable molar activity (66.2 ± 2.5 GBq/μmol). In vitro autoradiography revealed high PDE4B binding, while dynamic PET imaging demonstrated high in vivo specificity for PDE4B in rodent brain regions. Notably, [ 18 F]P4B-2412 exhibited excellent metabolic stability in vitro and in vivo . These findings establish [ 18 F]P4B-2412 as a promising PET probe for imaging PDE4B in vivo , offering a valuable tool for investigating neuroinflammation and advancing CNS drug development.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":557096,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9544,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1120882,"name":"Yinlong Li","orcid":"0000-0002-8864-1712","position":1,"is_corresponding":false},{"id":1409775,"name":"Siyan Feng","orcid":null,"position":2,"is_corresponding":false},{"id":428768,"name":"Jiahui Chen","orcid":"0000-0001-9186-1110","position":3,"is_corresponding":false},{"id":1120883,"name":"Xin Zhou","orcid":"0000-0002-1820-7830","position":4,"is_corresponding":false},{"id":1409307,"name":"Zhixu Zhang","orcid":"0000-0002-5455-5306","position":5,"is_corresponding":false},{"id":1409306,"name":"Zhenkun Sun","orcid":"0000-0002-5130-283X","position":6,"is_corresponding":false},{"id":338777,"name":"Jian Rong","orcid":"0000-0002-3960-1669","position":7,"is_corresponding":false},{"id":759836,"name":"Chunyu Zhao","orcid":"0000-0003-0168-2130","position":8,"is_corresponding":false},{"id":1149212,"name":"Ahmad Chaudhary","orcid":"0009-0007-0614-3335","position":9,"is_corresponding":false},{"id":719231,"name":"Jimmy S. Patel","orcid":"0000-0002-7322-7578","position":10,"is_corresponding":false},{"id":1332109,"name":"Yabiao Gao","orcid":"0000-0001-7600-9982","position":11,"is_corresponding":false},{"id":428769,"name":"Thomas Collier","orcid":"0000-0002-3757-4855","position":12,"is_corresponding":false},{"id":270762,"name":"Chongzhao Ran","orcid":"0000-0002-3892-4108","position":13,"is_corresponding":false},{"id":650240,"name":"Ahmed Haider","orcid":"0000-0002-5204-4473","position":14,"is_corresponding":false},{"id":295025,"name":"Hongjie Yuan","orcid":"0000-0002-8127-7145","position":15,"is_corresponding":false},{"id":338781,"name":"Steven H. Liang","orcid":"0000-0003-1413-6315","position":16,"is_corresponding":false},{"id":1323952,"name":"Zhendong Song","orcid":"0000-0002-1657-6325","position":0,"is_corresponding":true}],"reference_count":23,"raw_metadata":null,"created_at":"2026-07-19T02:55:13.130091Z","pmid":"39868192","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":[]}