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We report the synthesis, chemical characterization, and biological evaluation of two novel dimeric cyclic RGD-based molecular probes for the targeted imaging of\n \u03b1<\/jats:italic>\n \n V<\/jats:italic>\n <\/jats:sub>\n \u03b2<\/jats:italic>\n 3<\/jats:sub>\n activity (a radiolabeled version,\n 64<\/jats:sup>\n Cu-NOTA-PEG\n 4<\/jats:sub>\n -cRGD\n 2<\/jats:sub>\n , for PET imaging, and a fluorescent version, FITC-PEG\n 4<\/jats:sub>\n -cRGD\n 2<\/jats:sub>\n , for\n in vitro<\/jats:italic>\n work). We investigated the performance of this probe at the receptor, cell, organ, and whole-body levels, including its use to detect diabetes associated impairment of ischemia-induced myocardial angiogenesis. Both versions of the probe were found to be stable, demonstrated fast receptor association constants, and showed high specificity for\n \u03b1<\/jats:italic>\n \n V<\/jats:italic>\n <\/jats:sub>\n \u03b2<\/jats:italic>\n 3<\/jats:sub>\n in HUVECs (\n K<\/jats:italic>\n \n d<\/jats:italic>\n <\/jats:sub>\n \u2009~\u200935\u2009nM). Dynamic PET-CT imaging indicated rapid blood clearance via kidney filtration, and accumulation within\n \u03b1<\/jats:italic>\n \n V<\/jats:italic>\n <\/jats:sub>\n \u03b2<\/jats:italic>\n 3<\/jats:sub>\n -positive infarcted myocardium.\n 64<\/jats:sup>\n Cu-NOTA-PEG\n 4<\/jats:sub>\n -cRGD\n 2<\/jats:sub>\n demonstrated a favorable biodistribution, slow washout, and excellent performance with respect to the quality of the PET-CT images obtained. Importantly, the ratio of probe uptake in infarcted heart tissue compared to normal tissue was significantly higher in non-diabetic rats than in diabetic ones. Overall, our probes are promising agents for non-invasive quantitative imaging of\n \u03b1<\/jats:italic>\n \n V<\/jats:italic>\n <\/jats:sub>\n \u03b2<\/jats:italic>\n 3<\/jats:sub>\n expression, both\n in vitro<\/jats:italic>\n and\n in vivo<\/jats:italic>\n .\n <\/jats:p>","DOI":"10.1038\/s41598-017-03224-8","type":"journal-article","created":{"date-parts":[[2017,6,5]],"date-time":"2017-06-05T07:05:47Z","timestamp":1496646347000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Synthesis, Chemical Characterization and Multiscale Biological Evaluation of a Dimeric-cRGD Peptide for Targeted Imaging of \u03b1\n \n V\n \n \u03b2\n 3 Integrin Activity"],"prefix":"10.1038","volume":"7","author":[{"given":"Jamila","family":"Hedhli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrzej","family":"Czerwinski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Schuelke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agata","family":"P\u0142oska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pawe\u0142","family":"Sowinski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukas La","family":"Hood","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5613-3596","authenticated-orcid":false,"given":"Spencer B.","family":"Mamer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John A.","family":"Cole","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulina","family":"Czaplewska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maciej","family":"Banach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iwona T.","family":"Dobrucki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leszek","family":"Kalinowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Princess","family":"Imoukhuede","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6807-217X","authenticated-orcid":false,"given":"Lawrence W.","family":"Dobrucki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,6,9]]},"reference":[{"key":"3224_CR1","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1038\/nm0195-27","volume":"1","author":"J Folkman","year":"1995","unstructured":"Folkman, J. 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