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Joint inflammation and pathological growth of joint cartilage cause swollen and painful joints, which severely diminishes the patients\u2019 life quality. There is no causal treatment. Symptomatic therapies should start as early as possible to take maximal effect. Hence, diagnostic procedures capable of detecting affected joints before the onset of clinical symptoms are highly desirable. We explored the value of PET imaging of integrin subtypes \u03b1v\u03b23 and \u03b15\u03b21 for early detection of RA foci in collagen-induced arthritis (CIA) mouse models.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>Development of RA in CIA mice was monitored by paw scoring, and \u03b1v\u03b23- and \u03b15\u03b21-integrin expression was quantified by \u03bcPET using <jats:sup>68<\/jats:sup>Ga-Avebetrin and <jats:sup>68<\/jats:sup>Ga-Aquibeprin. For consecutive sections of selected decalcified joints (knee, ankle), arthritic degeneration and integrin expression were assessed by MOVAT staining and \u03b23\/\u03b15 immunohistochemistry (IHC), respectively. \u03b23- and \u03b15-IHC revealed elevated levels of both \u03b1v\u03b23- and \u03b15\u03b21-integrin in arthritic joints. Unlike \u03b1v\u03b23, \u03b15\u03b21 is strongly expressed in the proliferating synovial lining layer, which suggests that its presence is directly related to RA development. For mice with advanced RA (6\u2009weeks after CIA), PET signals for \u03b15\u03b21-integrin were substantially stronger (&gt;\u2009300% of baseline) than that of \u03b1v\u03b23-integrin (&lt;\u2009200%). A longitudinal PET follow-up revealed that the manifestation of clinical symptoms of RA is preceded by upregulation of \u03b15\u03b21- but not of \u03b1v\u03b23-integrin.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conclusion<\/jats:title>\n<jats:p>\u03b15\u03b21-integrin PET could add a new functional imaging aspect to the portfolio of RA diagnostics because it appears to be a sensitive biomarker for early RA development. We suggest \u03b15\u03b21-integrin PET as a valuable tool to achieve a higher precision for early diagnosis of RA, including initial staging, monitoring of the disease course, and drug treatment, and for planning of radiosynoviorthesis (RSO).<\/jats:p>\n<\/jats:sec>","DOI":"10.1186\/s13550-019-0541-6","type":"journal-article","created":{"date-parts":[[2019,9,9]],"date-time":"2019-09-09T14:03:23Z","timestamp":1568037803000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["In vivo imaging of early stages of rheumatoid arthritis by \u03b15\u03b21-integrin-targeted positron emission tomography"],"prefix":"10.1186","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3964-3391","authenticated-orcid":false,"given":"Johannes","family":"Notni","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian T.","family":"Gassert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"Steiger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Sommer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilko","family":"Weichert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernst J.","family":"Rummeny","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Schwaiger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Horst","family":"Kessler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reinhard","family":"Meier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie A.","family":"Kimm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,9,9]]},"reference":[{"key":"541_CR1","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1038\/nrd.2016.21","volume":"15","author":"K Chaudhari","year":"2016","unstructured":"Chaudhari K, Rizvi S, Syed BA. 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