{"doi":"10.2967/jnumed.123.266750","title":"Robust Quantification of Phosphodiesterase-4D in Monkey Brain with PET and<sup>11</sup>C-Labeled Radioligands That Avoid Radiometabolite Contamination","abstract":"Phosphodiesterase-4D (PDE4D) has emerged as a significant target for treating neuropsychiatric disorders, but no PET radioligand currently exists for robustly quantifying human brain PDE4D to assist biomedical research and drug discovery. A prior candidate PDE4D PET radioligand, namely [<sup>11</sup>C]T1650, failed in humans because of poor time stability of brain PDE4D-specific signal (indexed by total volume of distribution), likely due to radiometabolites accumulating in brain. Its nitro group was considered to be a source of the brain radiometabolites. <b>Methods:</b> We selected 5 high-affinity and selective PDE4D inhibitors, absent of a nitro group, from our prior structure–activity relationship study for evaluation as PET radioligands. <b>Results:</b> All 5 radioligands were labeled with <sup>11</sup>C (half-time, 20.4 min) in useful yields and with high molar activity. All displayed sizable PDE4D-specific signals in rhesus monkey brain. Notably, [<sup>11</sup>C]JMJ-81 and [<sup>11</sup>C]JMJ-129 exhibited excellent time stability of signal (total volume of distribution). Furthermore, as an example, [<sup>11</sup>C]JMJ-81 was found to be free of radiometabolites in ex vivo monkey brain, affirming that this radioligand can provide robust quantification of brain PDE4D with PET. <b>Conclusion:</b> Given their high similarity in structures and metabolic profiles, both [<sup>11</sup>C]JMJ-81 and [<sup>11</sup>C]JMJ-129 warrant further evaluation in human subjects. [<sup>11</sup>C]JMJ-129 shows a higher PDE4D specific-to-nonspecific binding ratio and will be the first to be evaluated.","journal":"Journal of Nuclear Medicine","year":2024,"id":479569,"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":0.9557,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1249645,"name":"Shiyu Tang","orcid":"0000-0001-6503-5878","position":1,"is_corresponding":false},{"id":934507,"name":"Madeline Jenkins","orcid":null,"position":2,"is_corresponding":false},{"id":1287946,"name":"Adrian Lee","orcid":"0000-0003-1617-9992","position":3,"is_corresponding":false},{"id":1318681,"name":"Bruny Kenou","orcid":"0000-0003-2021-6741","position":4,"is_corresponding":false},{"id":1288573,"name":"Carson Knoer","orcid":null,"position":5,"is_corresponding":false},{"id":713636,"name":"Jose Montero Santamaria","orcid":null,"position":6,"is_corresponding":false},{"id":734467,"name":"Shawn Wu","orcid":null,"position":7,"is_corresponding":false},{"id":394486,"name":"Jeih‐San Liow","orcid":"0000-0002-7878-1076","position":8,"is_corresponding":false},{"id":342708,"name":"Sami S. Zoghbi","orcid":"0000-0001-5613-8314","position":9,"is_corresponding":false},{"id":394493,"name":"Paolo Zanotti‐Fregonara","orcid":"0000-0001-9387-8397","position":10,"is_corresponding":false},{"id":237392,"name":"Robert B. Innis","orcid":"0000-0003-1238-7209","position":11,"is_corresponding":false},{"id":348139,"name":"Sanjay Telu","orcid":"0000-0001-5300-8725","position":12,"is_corresponding":false},{"id":342697,"name":"Victor W. Pike","orcid":"0000-0001-9032-2553","position":13,"is_corresponding":false},{"id":334467,"name":"Meijuan Jiang","orcid":"0000-0002-7918-7538","position":0,"is_corresponding":true}],"reference_count":41,"raw_metadata":null,"created_at":"2026-07-19T02:06:54.284166Z","pmid":"38423785","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":[]}