{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T16:34:19Z","timestamp":1789403659974,"version":"build-2803163510"},"reference-count":52,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,4,2]],"date-time":"2025-04-02T00:00:00Z","timestamp":1743552000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health","award":["R01 EB-019950-01A1"],"award-info":[{"award-number":["R01 EB-019950-01A1"]}]},{"name":"National Institutes of Health","award":["R01 GM124310-01"],"award-info":[{"award-number":["R01 GM124310-01"]}]},{"name":"National Institutes of Health","award":["CHE-1955349"],"award-info":[{"award-number":["CHE-1955349"]}]},{"name":"National Institutes of Health","award":["CHE-2247170"],"award-info":[{"award-number":["CHE-2247170"]}]},{"name":"National Science Foundation, Chemistry Division","award":["R01 EB-019950-01A1"],"award-info":[{"award-number":["R01 EB-019950-01A1"]}]},{"name":"National Science Foundation, Chemistry Division","award":["R01 GM124310-01"],"award-info":[{"award-number":["R01 GM124310-01"]}]},{"name":"National Science Foundation, Chemistry Division","award":["CHE-1955349"],"award-info":[{"award-number":["CHE-1955349"]}]},{"name":"National Science Foundation, Chemistry Division","award":["CHE-2247170"],"award-info":[{"award-number":["CHE-2247170"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>We report two conjugates of gem-diethyl pyrroline nitroxide radicals with D-mannosamine as potential metabolic organic radical contrast agents, mORCAs, circumventing the need for biorthogonal reactions. In-cell EPR spectroscopy, using Jurkat cells and analogous conjugate, based on a pyrrolidine nitroxide radical, shows an efficient incorporation of highly immobilized nitroxides, with a correlation time of \u03c4cor = 20 ns. In vivo MRI experiments in mice show that the paramagnetic nitroxide radical shortens the T1 and T2 relaxation times of protons in water located in the kidney and brain by only up to ~10% after 3 d. Ex vivo EPR spectroscopic analyses indicate that the contrast agents in mouse tissues are primarily localized in the kidney, lung, liver, heart, and blood, which primarily contain immobilized nitroxide radicals with \u03c4cor = 4\u20139 ns. The spin concentrations in tissues remain low (1\u20133 nmol g\u207b1) at 24 h after the third mORCA injection, approximately one to two orders of magnitude lower than those of ORCAFluor and BASP-ORCA (measured at ~24 h post-injection). These low spin concentrations explain the small proton T1 and T2 relaxation changes observed in in vivo MRI.<\/jats:p>","DOI":"10.3390\/molecules30071581","type":"journal-article","created":{"date-parts":[[2025,4,2]],"date-time":"2025-04-02T04:06:05Z","timestamp":1743566765000},"page":"1581","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Towards Metabolic Organic Radical Contrast Agents (mORCAs) for Magnetic Resonance Imaging"],"prefix":"10.3390","volume":"30","author":[{"given":"Shuyang","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Chemistry, University of Nebraska, Lincoln, NE 68588-0304, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabina","family":"Dhakal","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Nebraska, Lincoln, NE 68588-0304, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evan","family":"Curtis","sequence":"additional","affiliation":[{"name":"Department of Biological Systems Engineering, University of Nebraska, Lincoln, NE 68583-0900, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hunter","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Biological Systems Engineering, University of Nebraska, Lincoln, NE 68583-0900, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph T.","family":"Paletta","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Nebraska, Lincoln, NE 68588-0304, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Connor","family":"Gee","sequence":"additional","affiliation":[{"name":"Department of Biological Systems Engineering, University of Nebraska, Lincoln, NE 68583-0900, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0904-8329","authenticated-orcid":false,"given":"Suchada","family":"Rajca","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Nebraska, Lincoln, NE 68588-0304, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9847-783X","authenticated-orcid":false,"given":"Forrest","family":"Kievit","sequence":"additional","affiliation":[{"name":"Department of Biological Systems Engineering, University of Nebraska, Lincoln, NE 68583-0900, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrzej","family":"Rajca","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Nebraska, Lincoln, NE 68588-0304, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1148\/radiology.147.3.6844613","article-title":"Work in Progress: Nuclear Magnetic Resonance Study of a Paramagnetic Nitroxide Contrast Agent for Enhancement of Renal Structures in Experimental Animals","volume":"147","author":"Brasch","year":"1983","journal-title":"Radiology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2455","DOI":"10.1158\/1078-0432.CCR-05-2747","article-title":"High-Resolution Mapping of Tumor Redox Status by Magnetic Resonance Imaging Using Nitroxides as Redox-Sensitive Contrast Agents","volume":"12","author":"Matsumoto","year":"2006","journal-title":"Clin. 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