{"doi":"10.3390/ijms25147890","title":"[18F]Flotaza for Aβ Plaque Diagnostic Imaging: Evaluation in Postmortem Human Alzheimer’s Disease Brain Hippocampus and PET/CT Imaging in 5xFAD Transgenic Mice","abstract":"The diagnostic value of imaging Aβ plaques in Alzheimer’s disease (AD) has accelerated the development of fluorine-18 labeled radiotracers with a longer half-life for easier translation to clinical use. We have developed [18F]flotaza, which shows high binding to Aβ plaques in postmortem human AD brain slices with low white matter binding. We report the binding of [18F]flotaza in postmortem AD hippocampus compared to cognitively normal (CN) brains and the evaluation of [18F]flotaza in transgenic 5xFAD mice expressing Aβ plaques. [18F]Flotaza binding was assessed in well-characterized human postmortem brain tissue sections consisting of HP CA1-subiculum (HP CA1-SUB) regions in AD (n = 28; 13 male and 15 female) and CN subjects (n = 32; 16 male and 16 female). Adjacent slices were immunostained with anti-Aβ and analyzed using QuPath. In vitro and in vivo [18F]flotaza PET/CT studies were carried out in 5xFAD mice. Post-mortem human brain slices from all AD subjects were positively IHC stained with anti-Aβ. High [18F]flotaza binding was measured in the HP CA1-SUB grey matter (GM) regions compared to white matter (WM) of AD subjects with GM/WM > 100 in some subjects. The majority of CN subjects had no decipherable binding. Male AD exhibited greater WM than AD females (AD WM♂/WM♀ > 5; p < 0.001) but no difference amongst CN WM. In vitro studies in 5xFAD mice brain slices exhibited high binding [18F]flotaza ratios (>50 versus cerebellum) in the cortex, HP, and thalamus. In vivo, PET [18F]flotaza exhibited binding to Aβ plaques in 5xFAD mice with SUVR~1.4. [18F]Flotaza is a new Aβ plaque PET imaging agent that exhibited high binding to Aβ plaques in postmortem human AD. Along with the promising results in 5xFAD mice, the translation of [18F]flotaza to human PET studies may be worthwhile.","journal":"International Journal of Molecular Sciences","year":2024,"id":438735,"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":0.9506,"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":1242756,"name":"Harman S. Bath","orcid":null,"position":1,"is_corresponding":false},{"id":1130329,"name":"Jasmine Shergill","orcid":null,"position":2,"is_corresponding":false},{"id":725634,"name":"Christopher Liang","orcid":"0000-0001-9081-294X","position":3,"is_corresponding":false},{"id":1049091,"name":"Amina U. Syed","orcid":null,"position":4,"is_corresponding":false},{"id":1248870,"name":"Ambrose Loc T Ngo","orcid":"0009-0002-6993-9131","position":5,"is_corresponding":false},{"id":1248871,"name":"Fariha Karim","orcid":"0009-0001-3104-9523","position":6,"is_corresponding":false},{"id":256002,"name":"Geidy E. Serrano","orcid":"0000-0002-9527-2011","position":7,"is_corresponding":false},{"id":107088,"name":"Thomas G. Beach","orcid":"0000-0003-3296-6128","position":8,"is_corresponding":false},{"id":579729,"name":"Jogeshwar Mukherjee","orcid":"0000-0003-1009-877X","position":9,"is_corresponding":false},{"id":1065144,"name":"Yasmin K. Sandhu","orcid":null,"position":0,"is_corresponding":true}],"reference_count":66,"raw_metadata":null,"created_at":"2026-07-19T02:00:43.618468Z","pmid":"39063132","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":[]}