{"doi":"10.3390/molecules30204129","title":"The Evaluation of (1R,4R,7R,10R)-α,α′,α″,α‴-Tetramethyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic Acid (DOTMA) as a Chelator for Zirconium-89","abstract":"Recently, macrocycles such as 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) have been observed to form zirconium-89 (89Zr: t½ = 78.4 h, β+: 22.8%, Eβ+max = 901 keV; EC: 77%, Eγ = 909 keV)-complexes with excellent in vivo stability. In this report, we describe (1R,4R,7R,10R)-α,α′,α″,α‴-tetramethyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTMA) as an 89Zr chelator. Using [89Zr]ZrCl4, [89Zr]Zr-DOTMA was prepared in 99% radiochemical yield and a molar activity of 1055 ± 6 MBq/µmol. In vitro studies revealed a LogP value of −2.97± 0.02 and a radiometal complex that was inert when challenged with 1000-fold excess EDTA or high concentrations of biologically relevant metal ions. Finally, biodistribution studies revealed that the radiometal complex demonstrated in vivo behavior that was like [89Zr]Zr-DOTA and superior to [89Zr]Zr-DFO. Despite these promising observations, the elevated temperature required to form the [89Zr]Zr-DOTMA complex and the lack of derivatives available for bioconjugation will require additional ligand engineering to improve its utility for future nuclear medicine applications.","journal":"Molecules","year":2025,"id":547815,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9546,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1440592,"name":"Pere Miró","orcid":"0000-0002-3281-0708","position":1,"is_corresponding":false},{"id":1440593,"name":"Michael A. Sinnwell","orcid":"0000-0002-6733-8335","position":2,"is_corresponding":false},{"id":1441044,"name":"George Crull","orcid":null,"position":3,"is_corresponding":false},{"id":476647,"name":"Thaddeus J. Wadas","orcid":"0000-0002-9913-0336","position":4,"is_corresponding":false},{"id":476642,"name":"Darpan N. Pandya","orcid":"0000-0001-6288-5172","position":0,"is_corresponding":true}],"reference_count":63,"raw_metadata":null,"created_at":"2026-07-19T02:53:53.962932Z","pmid":"41157146","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":[]}