{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T06:49:51Z","timestamp":1787726991949,"version":"build-2784847793"},"reference-count":36,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2022,5,10]],"date-time":"2022-05-10T00:00:00Z","timestamp":1652140800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000849","name":"National Centre for the Replacement, Refinement and Reduction of Animals in Research","doi-asserted-by":"publisher","award":["NC\/M000141\/1"],"award-info":[{"award-number":["NC\/M000141\/1"]}],"id":[{"id":"10.13039\/501100000849","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012041","name":"Versus Arthritis","doi-asserted-by":"publisher","award":["20205"],"award-info":[{"award-number":["20205"]}],"id":[{"id":"10.13039\/501100012041","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012041","name":"Versus Arthritis","doi-asserted-by":"publisher","award":["21621"],"award-info":[{"award-number":["21621"]}],"id":[{"id":"10.13039\/501100012041","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Established MRI and emerging X-ray contrast agents for non-invasive imaging of articular cartilage rely on non-selective electrostatic interactions with negatively charged proteoglycans. These contrast agents have limited prognostic utility in diseases such as osteoarthritis (OA) due to the characteristic high turnover of proteoglycans. To overcome this limitation, we developed a radiocontrast agent that targets the type II collagen macromolecule in cartilage and used it to monitor disease progression in a murine model of OA.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>To confer radiopacity to cartilage contrast agents, the naturally occurring tyrosine derivative 3,5-diiodo-L-tyrosine (DIT) was introduced into a selective peptide for type II collagen. Synthetic DIT peptide derivatives were synthesised by Fmoc-based solid-phase peptide synthesis and binding to <jats:italic>ex vivo<\/jats:italic> mouse tibial cartilage evaluated by high-resolution micro-CT. Di-Iodotyrosinated Peptide Imaging of Cartilage (DIPIC) was performed <jats:italic>ex vivo<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> 4, 8 and 12 weeks in mice after induction of OA by destabilisation of the medial meniscus (DMM). Finally, human osteochondral plugs were imaged <jats:italic>ex vivo<\/jats:italic> using DIPIC.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Fifteen DIT peptides were synthesised and tested, yielding seven leads with varying cartilage binding strengths. DIPIC visualised <jats:italic>ex vivo<\/jats:italic> murine articular cartilage comparably to the <jats:italic>ex vivo<\/jats:italic> contrast agent phosphotungstic acid. Intra-articular injection of contrast agent followed by <jats:italic>in vivo<\/jats:italic> DIPIC enabled delineation of damaged murine articular cartilage. Finally, the translational potential of the contrast agent was confirmed by visualisation of <jats:italic>ex vivo<\/jats:italic> human cartilage explants.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>DIPIC has reduction and refinement implications in OA animal research and potential clinical translation to imaging human disease.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0268223","type":"journal-article","created":{"date-parts":[[2022,5,10]],"date-time":"2022-05-10T17:25:46Z","timestamp":1652203546000},"page":"e0268223","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":12,"title":["Imaging articular cartilage in osteoarthritis using targeted peptide radiocontrast agents"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3373-7714","authenticated-orcid":true,"given":"Milan M.","family":"Fowkes","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Das Neves Borges","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Cacho-Nerin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul E.","family":"Brennan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tonia L.","family":"Vincent","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ngee H.","family":"Lim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,5,10]]},"reference":[{"issue":"1","key":"pone.0268223.ref001","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.berh.2014.02.002","article-title":"The role of imaging in osteoarthritis","volume":"28","author":"FW Roemer","year":"2014","journal-title":"Best Practice & Research: Clinical Rheumatology"},{"issue":"2","key":"pone.0268223.ref002","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1152\/physrev.00049.2010","article-title":"A molecular imaging primer: modalities, imaging agents, and applications","volume":"92","author":"ML James","year":"2012","journal-title":"Physiological Reviews"},{"issue":"10","key":"pone.0268223.ref003","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1016\/j.joca.2015.05.026","article-title":"Compositional MRI techniques for evaluation of cartilage degeneration in osteoarthritis","volume":"23","author":"A Guermazi","year":"2015","journal-title":"Osteoarthritis Cartilage"},{"issue":"1","key":"pone.0268223.ref004","first-page":"179","article-title":"Use of CT Vs. 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