{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T03:22:37Z","timestamp":1788492157988,"version":"build-2803163510"},"reference-count":64,"publisher":"Wiley","issue":"31","license":[{"start":{"date-parts":[[2024,5,29]],"date-time":"2024-05-29T00:00:00Z","timestamp":1716940800000},"content-version":"am","delay-in-days":342,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#am"},{"start":{"date-parts":[[2023,6,22]],"date-time":"2023-06-22T00:00:00Z","timestamp":1687392000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000165","name":"Division of Chemistry","doi-asserted-by":"publisher","award":["CHE-1904780"],"award-info":[{"award-number":["CHE-1904780"]}],"id":[{"id":"10.13039\/100000165","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Angew Chem Int Ed"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    We report dissolution Dynamic Nuclear Polarization (d\u2010DNP) of [\n                    <jats:sup>15<\/jats:sup>\n                    N\n                    <jats:sub>3<\/jats:sub>\n                    ]metronidazole ([\n                    <jats:sup>15<\/jats:sup>\n                    N\n                    <jats:sub>3<\/jats:sub>\n                    ]MNZ) for the first time. Metronidazole is a clinically approved antibiotic, which can be potentially employed as a hypoxia\u2010sensing molecular probe using\n                    <jats:sup>15<\/jats:sup>\n                    N hyperpolarized (HP) nucleus. The DNP process is very efficient for [\n                    <jats:sup>15<\/jats:sup>\n                    N\n                    <jats:sub>3<\/jats:sub>\n                    ]MNZ with an exponential build\u2010up constant of 13.8\u2005min using trityl radical. After dissolution and sample transfer to a nearby 4.7\u2005T Magnetic Resonance Imaging scanner, HP [\n                    <jats:sup>15<\/jats:sup>\n                    N\n                    <jats:sub>3<\/jats:sub>\n                    ]MNZ lasted remarkably long with T\n                    <jats:sub>1<\/jats:sub>\n                    values up to 343\u2005s and\n                    <jats:sup>15<\/jats:sup>\n                    N polarizations up to 6.4\u2009%. A time series of HP [\n                    <jats:sup>15<\/jats:sup>\n                    N\n                    <jats:sub>3<\/jats:sub>\n                    ]MNZ images was acquired in vitro using a steady state free precession sequence on the\n                    <jats:sup>15<\/jats:sup>\n                    NO\n                    <jats:sub>2<\/jats:sub>\n                    peak. The signal lasted over 13\u2005min with notably long T\n                    <jats:sub>2<\/jats:sub>\n                    of 20.5\u2005s. HP [\n                    <jats:sup>15<\/jats:sup>\n                    N\n                    <jats:sub>3<\/jats:sub>\n                    ]MNZ was injected in the tail vein of a healthy rat, and dynamic spectroscopy was performed over the rat brain. The in vivo HP\n                    <jats:sup>15<\/jats:sup>\n                    N signals persisted over 70\u2005s, demonstrating an unprecedented opportunity for in vivo studies.\n                  <\/jats:p>","DOI":"10.1002\/anie.202219181","type":"journal-article","created":{"date-parts":[[2023,5,29]],"date-time":"2023-05-29T16:20:11Z","timestamp":1685377211000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Development of Dissolution Dynamic Nuclear Polarization of [\n                    <sup>15<\/sup>\n                    N\n                    <sub>3<\/sub>\n                    ]Metronidazole: A Clinically Approved Antibiotic"],"prefix":"10.1002","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1388-0559","authenticated-orcid":false,"given":"David O.","family":"Guarin","sequence":"first","affiliation":[{"name":"Department of Radiology Athinoula A. Martinos Center for Biomedical Imaging Massachusetts General Hospital  149 13th St. MA 02129 Charlestown USA"},{"name":"Polarize ApS.  Asmussens Alle 1 1808 Frederiksberg Denmak"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sameer M.","family":"Joshi","sequence":"additional","affiliation":[{"name":"Department of Chemistry Integrative Biosciences (Ibio) Karmanos Cancer Institute (KCI) Wayne State University  MI 48202 Detroit USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Samoilenko","sequence":"additional","affiliation":[{"name":"Department of Chemistry Integrative Biosciences (Ibio) Karmanos Cancer Institute (KCI) Wayne State University  MI 48202 Detroit USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad S. H.","family":"Kabir","sequence":"additional","affiliation":[{"name":"Department of Chemistry Integrative Biosciences (Ibio) Karmanos Cancer Institute (KCI) Wayne State University  MI 48202 Detroit USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin E.","family":"Hardy","sequence":"additional","affiliation":[{"name":"Department of Radiology Athinoula A. Martinos Center for Biomedical Imaging Massachusetts General Hospital  149 13th St. MA 02129 Charlestown USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsush M.","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Brain and Cognitive Sciences McGovern Institute for Brain Research Massachusetts Institute of Technology  MA 02139 Cambridge USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan H.","family":"Ardenkjaer\u2010Larsen","sequence":"additional","affiliation":[{"name":"Polarize ApS.  Asmussens Alle 1 1808 Frederiksberg Denmak"},{"name":"Department of Health Technology Technical University of Denmark  348, \u00d8rsteds Pl. 2800 Kongens Lyngby Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8745-8801","authenticated-orcid":false,"given":"Eduard Y.","family":"Chekmenev","sequence":"additional","affiliation":[{"name":"Department of Chemistry Integrative Biosciences (Ibio) Karmanos Cancer Institute (KCI) Wayne State University  MI 48202 Detroit USA"},{"name":"Russian Academy of Sciences (RAS)  14 Leninskiy Prospekt 119991 Moscow Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9986-5327","authenticated-orcid":false,"given":"Yi\u2010Fen","family":"Yen","sequence":"additional","affiliation":[{"name":"Department of Radiology Athinoula A. Martinos Center for Biomedical Imaging Massachusetts General Hospital  149 13th St. MA 02129 Charlestown USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,6,22]]},"reference":[{"key":"e_1_2_7_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.acra.2006.06.001"},{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.23753"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.21253"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3006070"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/nop043"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.111.024919"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.20013"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.20247"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.25071"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms15126"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07017"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/nbm.1742"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1259\/bjr\/26631666"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neo.2018.09.006"},{"key":"e_1_2_7_15_1","first-page":"4","volume-title":"EMagRes","author":"Goodson B. M.","year":"2015"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1039\/D2SC01264B"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.26004"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1103\/PhysRev.109.1441"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1088\/0034-4885\/41\/3\/002"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1168877"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmre.2001.2341"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1103\/PhysRevLett.57.2645"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrc.4280"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmr.2016.01.015"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmr.2015.12.024"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmr.2015.12.027"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1733835100"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmr.2019.06.001"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1593\/neo.101102"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja8001293"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jpcb.0c02583"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1039\/C6SC04043H"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201905483"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.26104"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmr.2013.04.010"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja9049355"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.22484"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2016.00059"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jpcc.8b00283"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep40104"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.1501438"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1039\/c002309b"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.28578"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.14.1.150-164.2001"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.2009.01195.x"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.7b01678"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/chem.201901192"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep16802"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-022-01341-9"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202011698"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1039\/D0CC03994B"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.6b04784"},{"key":"e_1_2_7_53_1","unstructured":"Food and Drug Administration of the United States \u201cMETRONIDAZOLE Injection USP \u201d can be found underhttps:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2018\/018890s052lbl.pdf. 2018."},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1021\/acssensors.2c01715"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1002\/nbm.1481"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(01)63342-1"},{"key":"e_1_2_7_57_1","first-page":"87","volume":"40","author":"Burgess J. L.","year":"1998","journal-title":"Vet. Hum. Toxicol."},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0090-4295(98)00347-1"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-2952(03)00002-9"},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.10421"},{"key":"e_1_2_7_61_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00330-003-1957-x"},{"key":"e_1_2_7_62_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.10530"},{"key":"e_1_2_7_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmr.2020.106691"},{"key":"e_1_2_7_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmr.2017.06.009"}],"container-title":["Angewandte Chemie International Edition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/am-pdf\/10.1002\/anie.202219181","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/anie.202219181","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,19]],"date-time":"2023-08-19T01:20:45Z","timestamp":1692408045000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/anie.202219181"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,22]]},"references-count":64,"journal-issue":{"issue":"31","published-print":{"date-parts":[[2023,8]]}},"alternative-id":["10.1002\/anie.202219181"],"URL":"https:\/\/doi.org\/10.1002\/anie.202219181","archive":["Portico"],"relation":{},"ISSN":["1433-7851","1521-3773"],"issn-type":[{"value":"1433-7851","type":"print"},{"value":"1521-3773","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,22]]},"assertion":[{"value":"2022-12-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-06-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e202219181"}}