{"doi":"10.3390/molecules28155769","title":"[125I]INFT: Synthesis and Evaluation of a New Imaging Agent for Tau Protein in Post-Mortem Human Alzheimer’s Disease Brain","abstract":"Aggregation of Tau protein into paired helical filaments causing neurofibrillary tangles (NFT) is a neuropathological feature in Alzheimer’s disease (AD). This study aimed to develop and evaluate the effectiveness of a novel radioiodinated tracer, 4-[125I]iodo-3-(1H-pyrrolo[2,3-c]pyridine-1-yl)pyridine ([125I]INFT), for binding to Tau protein in postmortem human AD brain. Radiosynthesis of [125I]INFT was carried out using electrophilic destannylation by iodine-125 and purified chromatographically. Computational modeling of INFT binding on Tau fibril was compared with IPPI. In vitro, autoradiography studies were conducted with [125I]INFT for Tau in AD and cognitively normal (CN) brains. [125I]INFT was produced in >95% purity. Molecular modeling of INFT revealed comparable binding energies to IPPI at site-1 of the Tau fibril with an affinity of IC50 = 7.3 × 10−8 M. Binding of [125I]INFT correlated with the presence of Tau in the AD brain, confirmed by anti-Tau immunohistochemistry. The ratio of average grey matter (GM) [125I]INFT in AD versus CN was found to be 5.9, and AD GM/white matter (WM) = 2.5. Specifically bound [125I]INFT to Tau in AD brains was displaced by IPPI (>90%). Monoamine oxidase inhibitor deprenyl had no effect and clorgyline had little effect on [125I]INFT binding. [125I]INFT is a less lipophilic imaging agent for Tau in AD.","journal":"Molecules","year":2023,"id":352842,"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":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9596,"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":725634,"name":"Christopher Liang","orcid":"0000-0001-9081-294X","position":1,"is_corresponding":false},{"id":1065144,"name":"Yasmin K. Sandhu","orcid":null,"position":2,"is_corresponding":false},{"id":579729,"name":"Jogeshwar Mukherjee","orcid":"0000-0003-1009-877X","position":3,"is_corresponding":false},{"id":1065147,"name":"Roz R. Limpengco","orcid":null,"position":0,"is_corresponding":true}],"reference_count":30,"raw_metadata":null,"created_at":"2026-07-19T01:12:54.209378Z","pmid":"37570739","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":[]}