{"doi":"10.1002/ejic.202300457","title":"Construction of the Bioconjugate Py‐Macrodipa‐PSMA and Its In Vivo Investigations with Large <sup>132/135</sup>La<sup>3+</sup> and Small <sup>47</sup>Sc<sup>3+</sup> Radiometal Ions","abstract":"Abstract To harness radiometals in clinical settings, a chelator forming a stable complex with the metal of interest and targets the desired pathological site is needed. Toward this goal, we previously reported a unique set of chelators that can stably bind to both large and small metal ions, via a conformational switch. Within this chelator class, py‐macrodipa is particularly promising based on its ability to stably bind several medicinally valuable radiometals including large 132/135 La 3+ , 213 Bi 3+ , and small 44 Sc 3+ . Here, we report a 10‐step organic synthesis of its bifunctional analogue py‐macrodipa‐NCS, which contains an amine‐reactive −NCS group that is amenable for bioconjugation reactions to targeting vectors. The hydrolytic stability of py‐macordipa‐NCS was assessed, revealing a half‐life of 6.0 d in pH 9.0 aqueous buffer. This bifunctional chelator was then conjugated to a prostate‐specific membrane antigen (PSMA)‐binding moiety, yielding the bioconjugate py‐macrodipa‐PSMA, which was subsequently radiolabeled with large 132/135 La 3+ and small 47 Sc 3+ , revealing efficient and quantitative complex formation. The resulting radiocomplexes were injected into mice bearing both PSMA‐expressing and PSMA‐non‐expressing tumor xenografts to determine their biodistribution patterns, revealing delivery of both 132/135 La 3+ and 47 Sc 3+ to PSMA+ tumor sites. However, partial radiometal dissociation was observed, suggesting that py‐macrodipa‐PSMA needs further structural optimization.","journal":"European Journal of Inorganic Chemistry","year":2023,"id":348447,"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":11,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9505,"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":1090715,"name":"Kirsten Martin","orcid":"0000-0002-0638-0169","position":1,"is_corresponding":false},{"id":1087200,"name":"Dariusz Śmiłowicz","orcid":null,"position":2,"is_corresponding":false},{"id":402471,"name":"Eduardo Aluicio‐Sarduy","orcid":"0000-0002-7889-9162","position":3,"is_corresponding":false},{"id":700953,"name":"Shelbie J. Cingoranelli","orcid":"0009-0002-5578-0342","position":4,"is_corresponding":false},{"id":364750,"name":"Suzanne E. Lapi","orcid":"0000-0003-0090-0191","position":5,"is_corresponding":false},{"id":244590,"name":"Jonathan W. Engle","orcid":"0000-0002-3399-7228","position":6,"is_corresponding":false},{"id":327011,"name":"Eszter Boros","orcid":"0000-0002-4186-6586","position":7,"is_corresponding":false},{"id":327012,"name":"Justin J. Wilson","orcid":"0000-0002-4086-7982","position":8,"is_corresponding":false},{"id":878311,"name":"Aohan Hu","orcid":"0000-0002-9720-3159","position":0,"is_corresponding":true}],"reference_count":38,"raw_metadata":null,"created_at":"2026-07-19T01:12:06.040073Z","pmid":"38495596","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":[]}