{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:59:38Z","timestamp":1785437978420,"version":"3.56.0"},"reference-count":46,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T00:00:00Z","timestamp":1777248000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002428","name":"FWF Austrian Science Fund","doi-asserted-by":"publisher","award":["Grant-DOI: 10.55776\/T1145"],"award-info":[{"award-number":["Grant-DOI: 10.55776\/T1145"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002428","name":"FWF Austrian Science Fund","doi-asserted-by":"publisher","award":["Grant-DOI: 10.55776\/PAT8469124"],"award-info":[{"award-number":["Grant-DOI: 10.55776\/PAT8469124"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]},{"award":["Grant-DOI: 10.55776\/T1145"],"award-info":[{"award-number":["Grant-DOI: 10.55776\/T1145"]}],"id":[{"id":"https:\/\/ror.org\/013tf3c58","id-type":"ROR","asserted-by":"publisher"}]},{"award":["Grant-DOI: 10.55776\/PAT8469124"],"award-info":[{"award-number":["Grant-DOI: 10.55776\/PAT8469124"]}],"id":[{"id":"https:\/\/ror.org\/013tf3c58","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background: Paramagnetic manganese (Mn(II)) has emerged as a promising alternative to gadolinium-based contrast agents (GBCAs) due to its favorable magnetic properties. Despite extensive research, no Mn-based agent has yet achieved clinical translation. Because free Mn(II) is toxic, macromolecular complexes incorporating stable macrocyclic DOTA chelators conjugated to polysaccharides may enhance coordination stability and improve the safety profile of Mn(II)-based contrast agents. Methods: Two chemical routes, maleimide- and ester-mediated, were evaluated for covalent coupling of DOTA-based macrocyclic ligands to the backbone of selected poly- and oligosaccharides. Subsequently, DOTA-modified carboxymethyldextran, aminodextran, and chitosan oligosaccharide were labeled with paramagnetic Mn(II) under mild conditions. ATR-FTIR confirmed the successful conjugation of DOTA chelators to the sugar backbone. The conjugates were further characterized by DLS, ICP-MS, and FPLC. In vitro relaxivity was measured at high field strength to evaluate MRI performance. In vivo contrast efficacy was first assessed using in ovo MRI in chicken embryos and subsequently evaluated by biodistribution studies in nude mice. Results: In vitro relaxivity studies demonstrated higher signal enhancement of the poly-\/oligosaccharide-DOTA-Mn(II) conjugates compared with MnCl2 and the clinical agent gadoteridol (ProHance\u00ae). In ovo MRI showed persistent vascular enhancement up to 120 min, while in nude mice, contrast enhancement was observed in the liver, kidneys, and gallbladder 40 min post-injection. Conclusions: Mn(II)-tagged sugar-based imaging probes may offer a promising non-gadolinium alternative to GBCAs, with tunable biodistribution profiles depending on carrier molecular weight.<\/jats:p>","DOI":"10.3390\/pharmaceutics18050530","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T09:46:11Z","timestamp":1777455971000},"page":"530","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mn(II)-Tagged DOTA-Modified Sugar-Based Biopolymers as Gadolinium-Free Contrast Agents for Magnetic Resonance Imaging"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0312-6461","authenticated-orcid":false,"given":"Irena","family":"Pashkunova-Martic","sequence":"first","affiliation":[{"name":"Department of Biomedical Imaging and Image-Guided Therapy, Division of Molecular and Structural Preclinical Imaging, Medical University of Vienna & General Hospital of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria"},{"name":"Institute of Inorganic Chemistry, Faculty of Chemistry, University of Vienna, Waehringer Strasse 42, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1830-8113","authenticated-orcid":false,"given":"Joachim","family":"Friske","sequence":"additional","affiliation":[{"name":"Department of Biomedical Imaging and Image-Guided Therapy, Division of Molecular and Structural Preclinical Imaging, Medical University of Vienna & General Hospital of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvester J.","family":"Bartsch","sequence":"additional","affiliation":[{"name":"Department of Biomedical Imaging and Image-Guided Therapy, Division of Molecular and Structural Preclinical Imaging, Medical University of Vienna & General Hospital of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria"},{"name":"Department of Nuclear Medicine, TUM Klinikum Rechts Der Isar, Technical University of Munich, 80333 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5897-7409","authenticated-orcid":false,"given":"Daniela","family":"Prinz","sequence":"additional","affiliation":[{"name":"Department of Biomedical Imaging and Image-Guided Therapy, Division of Molecular and Structural Preclinical Imaging, Medical University of Vienna & General Hospital of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8154-5680","authenticated-orcid":false,"given":"Theresa","family":"Balber","sequence":"additional","affiliation":[{"name":"Department of Biomedical Imaging and Image-Guided Therapy, Division of Nuclear Medicine, Medical University of Vienna & General Hospital of Vienna, Waehringer Guertel 18\u201320, 1090 Vienna, Austria"},{"name":"Joint Applied Medicinal Radiochemistry Facility, University of Vienna and Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4544-2438","authenticated-orcid":false,"given":"Verena","family":"Pichler","sequence":"additional","affiliation":[{"name":"Joint Applied Medicinal Radiochemistry Facility, University of Vienna and Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Department of Pharmaceutical Sciences, University of Vienna, Josef-Holaubek-Platz 2 (UZA II), 1090 Vienna, Austria"},{"name":"Department of Pharmacy, University of Oslo, Problemveien 11, 0313 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dieter","family":"Baurecht","sequence":"additional","affiliation":[{"name":"Department of Physical Chemistry, Faculty of Chemistry, University of Vienna, Waehringer Strasse 42, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernhard K.","family":"Keppler","sequence":"additional","affiliation":[{"name":"Institute of Inorganic Chemistry, Faculty of Chemistry, University of Vienna, Waehringer Strasse 42, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3169-778X","authenticated-orcid":false,"given":"Thomas H.","family":"Helbich","sequence":"additional","affiliation":[{"name":"Department of Biomedical Imaging and Image-Guided Therapy, Division of Molecular and Structural Preclinical Imaging, Medical University of Vienna & General Hospital of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1021\/acs.chemrev.8b00363","article-title":"Chemistry of MRI Contrast 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