{"doi":"10.1021/acs.jpcb.5c05707","title":"<sup>1</sup> H/ <sup>15</sup> N NMR and Low-Field <sup>1</sup> H MRI of SABRE-Hyperpolarized Pyrazinamide─An Approved Antibiotic and Potential MRI Contrast Agent","abstract":"Pyrazinamide (PZA), an FDA-approved antibiotic, was investigated for potential use as a hyperpolarized MRI contrast agent. PZA was readily hyperpolarized via parahydrogen-based NMR Signal Amplification By Reversible Exchange (SABRE) at ∼5.5 mT, allowing 1 H polarization and relaxation dynamics to be characterized. More importantly, performing SABRE hyperpolarization in the microtesla regime (i.e., SABRE in SHield Enables Alignment Transfer to Heteronuclei, SABRE-SHEATH) allowed direct detection of enhanced 15 N NMR and corresponding polarization/relaxation dynamics to be characterized in this system for the first time, despite the low natural abundance of 15 N. Initial experiments detected at 9.4 T following SABRE-SHEATH at 0.2 μT permitted observation of a single 15 N resonance at 332.7 ppm (tentatively assigned to the ring N site meta to the amide group, based on the 1 H enhancement pattern, suggesting the less sterically hindered N site dominates this substrate’s interaction with the Ir-based SABRE catalyst). Direct SABRE-SHEATH 15 N hyperpolarization using a more optimized setup (with respect to mixing field, temperature, p -H 2 flow rate, etc.) that is directly coupled to a 1.4 T benchtop NMR system resulted in improved detection sensitivity, including 15 N enhancements of >140,000-fold for the primary 15 N resonance (corresponding to a polarization of ∼7% with substrate concentration of over 100 mM). This effort also yielded a 15 N T 1 measurement for PZA of over 2 min at 1.4 T. Finally, the potential utility of hyperpolarized PZA as a contrast agent was also demonstrated via quantitative 1 H MRI studies performed using a low-field (64 mT) portable “point-of-care” clinical scanner.","journal":"The Journal of Physical Chemistry B","year":2025,"id":579749,"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":0,"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":false,"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":1260741,"name":"Anthony F. Petrilla","orcid":null,"position":1,"is_corresponding":false},{"id":753812,"name":"Ishani M. Senanayake","orcid":"0009-0003-4772-2983","position":2,"is_corresponding":false},{"id":1260259,"name":"N Iqbal","orcid":"0009-0002-1280-9432","position":3,"is_corresponding":false},{"id":1386621,"name":"Joseph Gyesi","orcid":"0000-0002-1672-0147","position":4,"is_corresponding":false},{"id":1490664,"name":"Jasilyn Westerfield","orcid":null,"position":5,"is_corresponding":false},{"id":1260738,"name":"Praveen J. Daluwathumullagamage","orcid":null,"position":6,"is_corresponding":false},{"id":477784,"name":"Roman V. Shchepin","orcid":"0000-0001-9135-3036","position":7,"is_corresponding":false},{"id":760900,"name":"Sudarshan Ragunathan","orcid":"0000-0002-2871-1758","position":8,"is_corresponding":false},{"id":402028,"name":"Eduard Y. Chekmenev","orcid":"0000-0002-8745-8801","position":9,"is_corresponding":false},{"id":402030,"name":"Boyd M. Goodson","orcid":"0000-0001-6079-5077","position":10,"is_corresponding":false},{"id":1260740,"name":"Zahid Siraj","orcid":null,"position":0,"is_corresponding":true}],"reference_count":64,"raw_metadata":null,"created_at":"2026-07-19T02:58:34.718602Z","pmid":"41171728","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":[]}