{"doi":"10.3390/ph16020194","title":"In Vivo Imaging and Kinetic Modeling of Novel Glycogen Synthase Kinase-3 Radiotracers [11C]OCM-44 and [18F]OCM-50 in Non-Human Primates","abstract":"Glycogen synthase kinase 3 (GSK-3) is a potential therapeutic target for a range of neurodegenerative and psychiatric disorders. The goal of this work was to evaluate two leading GSK-3 positron emission tomography (PET) radioligands, [11C]OCM-44 and [18F]OCM-50, in non-human primates to assess their potential for clinical translation. A total of nine PET scans were performed with the two radiotracers using arterial blood sampling in adult rhesus macaques. Brain regional time-activity curves were extracted and fitted with one- and two-tissue compartment models using metabolite-corrected arterial input functions. Target selectivity was assessed after pre-administration of the GSK-3 inhibitor PF-04802367 (PF-367, 0.03–0.25 mg/kg). Both radiotracers showed good brain uptake and distribution throughout grey matter. [11C]OCM-44 had a free fraction in the plasma of 3% at baseline and was metabolized quickly. The [11C]OCM-44 volume of distribution (VT) values in the brain increased with time; VT values from models fitted to truncated 60-min scan data were 1.4–2.9 mL/cm3 across brain regions. The plasma free fraction was 0.6% for [18F]OCM-50 and VT values (120-min) were 0.39–0.87 mL/cm3 in grey matter regions. After correcting for plasma free fraction increases during blocking scans, reductions in regional VT indicated >80% target occupancy by 0.1 mg/kg of PF-367 for both radiotracers, supporting target selectivity in vivo. [11C]OCM-44 and [18F]OCM-50 warrant further evaluation as radioligands for imaging GSK-3 in the brain, though radio-metabolite accumulation may confound image analysis.","journal":"Pharmaceuticals","year":2023,"id":358971,"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":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9538,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":673370,"name":"Ming‐Qiang Zheng","orcid":null,"position":1,"is_corresponding":false},{"id":822586,"name":"Daniel Holden","orcid":"0000-0001-7585-4463","position":2,"is_corresponding":false},{"id":823127,"name":"Zachary Felchner","orcid":null,"position":3,"is_corresponding":false},{"id":3069,"name":"Li Zhang","orcid":"0000-0002-3617-2627","position":4,"is_corresponding":false},{"id":1109318,"name":"Yanjiang Han","orcid":"0000-0002-1987-503X","position":5,"is_corresponding":false},{"id":503254,"name":"Jim Ropchan","orcid":"0000-0002-1105-7489","position":6,"is_corresponding":false},{"id":235261,"name":"Richard E. Carson","orcid":"0000-0002-9338-7966","position":7,"is_corresponding":false},{"id":345082,"name":"Neil Vasdev","orcid":"0000-0002-2087-5125","position":8,"is_corresponding":false},{"id":235260,"name":"Yiyun Huang","orcid":"0000-0002-6757-3220","position":9,"is_corresponding":false},{"id":743135,"name":"Kelly Smart","orcid":"0000-0002-4775-6943","position":0,"is_corresponding":true}],"reference_count":27,"raw_metadata":null,"created_at":"2026-07-19T01:13:48.379546Z","pmid":"37259346","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":[]}