{"doi":"10.2967/jnumed.124.267482","title":"Development of a<sup>213</sup>Bi-Labeled Pyridyl Benzofuran for Targeted α-Therapy of Amyloid-β Aggregates","abstract":"Alzheimer disease is a neurodegenerative disorder with limited treatment options. It is characterized by the presence of several biomarkers, including amyloid-β aggregates, which lead to oxidative stress and neuronal decay. Targeted α-therapy (TAT) has been shown to be efficacious against metastatic cancer. TAT takes advantage of tumor-localized α-particle emission to break disease-associated covalent bonds while minimizing radiation dose to healthy tissues due to the short, micrometer-level, distances traveled. We hypothesized that TAT could be used to break covalent bonds within amyloid-β aggregates and facilitate natural plaque clearance mechanisms. <b>Methods:</b> We synthesized a <sup>213</sup>Bi-chelate–linked benzofuran pyridyl derivative (BiBPy) and generated [<sup>213</sup>Bi]BiBPy, with a specific activity of 120.6 GBq/μg, dissociation constant of 11 ± 1.5 nM, and logP of 0.14 ± 0.03. <b>Results:</b> As the first step toward the validation of [<sup>213</sup>Bi]BiBPy as a TAT agent for the reduction of Alzheimer disease–associated amyloid-β, we showed that brain homogenates from APP/PS1 double-transgenic male mice (6–9 mo old) incubated with [<sup>213</sup>Bi]BiBPy exhibited a marked reduction in amyloid-β plaque concentration as measured using both enzyme-linked immunosorbent and Western blotting assays, with a half-maximal effective concentration of 3.72 kBq/pg. <b>Conclusion:</b> This [<sup>213</sup>Bi]BiBPy-concentration–dependent activity shows that TAT can reduce amyloid plaque concentration in&nbsp;vitro and supports the development of targeting systems for in&nbsp;vivo validations.","journal":"Journal of Nuclear Medicine","year":2024,"id":464298,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9559,"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":454710,"name":"Emily K. Kirkeby","orcid":"0000-0003-4080-7960","position":1,"is_corresponding":false},{"id":388366,"name":"Donna J. Cross","orcid":"0000-0003-1918-2214","position":2,"is_corresponding":false},{"id":751484,"name":"Satoshi Minoshima","orcid":"0000-0002-0043-3047","position":3,"is_corresponding":false},{"id":454711,"name":"Andrew G. Roberts","orcid":"0000-0002-2221-534X","position":4,"is_corresponding":false},{"id":1295324,"name":"Tara E. Mastren","orcid":null,"position":5,"is_corresponding":false},{"id":1295323,"name":"Aidan A. Bender","orcid":null,"position":0,"is_corresponding":true}],"reference_count":43,"raw_metadata":null,"created_at":"2026-07-19T02:04:37.468651Z","pmid":"39054283","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":[]}