{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T23:37:24Z","timestamp":1770334644881,"version":"3.49.0"},"posted":{"date-parts":[[2026,1,23]]},"group-title":"Bioengineering","reference-count":55,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T00:00:00Z","timestamp":1769126400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"name":"Portugal 2020 program","award":["LABEL\u2019 (POCI-01-0247-FEDER-049268)"],"award-info":[{"award-number":["LABEL\u2019 (POCI-01-0247-FEDER-049268)"]}]},{"name":"FCT project","award":["TargetingHeart 2022.02803.PTDC"],"award-info":[{"award-number":["TargetingHeart 2022.02803.PTDC"]}]},{"name":"FCT project","award":["2023.15026.PEX"],"award-info":[{"award-number":["2023.15026.PEX"]}]},{"name":"European Union\u2019s Horizon Europe research and innovation programme","award":["Pizo4spine- grant agreement No 101098597"],"award-info":[{"award-number":["Pizo4spine- grant agreement No 101098597"]}]},{"name":"European Union or the European Health and Digital Executive Agency","award":["Reborn- 101091852"],"award-info":[{"award-number":["Reborn- 101091852"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,1,23]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Both for diagnostic purposes and regenerative medicine, it is essential to develop advanced imaging platforms capable of tracking the biodistribution of small extracellular vesicles (sEVs), as current methods are limited by inadequate resolution and sensitivity. In this study, we introduce a novel labeling strategy utilizing the radioisotope zirconium-89 (\n                  <jats:sup>89<\/jats:sup>\n                  Zr), which boasts a half-life of 78.4 h and is cost-effective to produce. To achieve this, we designed a new chelator tailored for\n                  <jats:sup>89<\/jats:sup>\n                  Zr\n                  <jats:sup>4+<\/jats:sup>\n                  that offers enhanced stability compared to the conventional deferoxamine (DFO). This chelator forms a robust complex with\n                  <jats:sup>89<\/jats:sup>\n                  Zr\n                  <jats:sup>4+<\/jats:sup>\n                  at room temperature, suitable for sEV labeling for PET imaging applications. The radiolabeling process involved a two-step procedure: first, conjugation of the chelator to the sEVs, and second, radiolabeling with\n                  <jats:sup>89<\/jats:sup>\n                  Zr\n                  <jats:sup>4+<\/jats:sup>\n                  . The resulting sEV-L1-Zr demonstrated a radiochemical yield of approximately 60% and maintained around 80% stability in plasma over seven days. Importantly, our modifications did not alter the morphology, surface protein composition, internal RNA content, or bioactivity of the sEVs. We successfully visualized sEVs at very low doses in the mouse heart following intravenous injection of sEV-L1-Zr. Additionally,\n                  <jats:italic>ex vivo<\/jats:italic>\n                  experiments using a Langendorff rat heart perfusion model confirmed targeted accumulation of the vesicles in cardiomyocytes as compared to other cells in the heart compartment. This approach provides a promising platform for sensitive and stable in\n                  <jats:italic>vivo<\/jats:italic>\n                  tracking of sEVs, advancing their application in both diagnostic imaging and regenerative therapies.\n                <\/jats:p>","DOI":"10.64898\/2026.01.21.700868","type":"posted-content","created":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T03:05:10Z","timestamp":1769223910000},"source":"Crossref","is-referenced-by-count":0,"title":["A room-temperature \u2078\u2079Zr\u2074\u207a radiolabelling strategy for small extracellular vesicles with enhanced plasma stability for PET Imaging"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7214-1473","authenticated-orcid":false,"given":"Arnab","family":"Banerjee","sequence":"first","affiliation":[{"name":"Institute of Pharmacology and Experimental Therapeutics, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"CNC-Center for Neurosciences and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal"}]},{"given":"Ivanna","family":"Hrynchak","sequence":"additional","affiliation":[{"name":"ICNAS \u2013 Institute for Nuclear Sciences Applied to Health; University of Coimbra, Coimbra-3000-548, Portugal"},{"name":"Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), University of Coimbra, Coimbra-3000-548, Portugal"},{"name":"Institute for Nuclear Sciences Applied to Health (ICNAS Pharma), Polo das Ci\u00eancias da Sa\u00fade, University of Coimbra, 3000-548 Coimbra, Portugal"}]},{"given":"Carlos","family":"Jesus","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Experimental Therapeutics, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"CNC-Center for Neurosciences and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal"}]},{"given":"Jos\u00e9","family":"Sereno","sequence":"additional","affiliation":[{"name":"ICNAS \u2013 Institute for Nuclear Sciences Applied to Health; University of Coimbra, Coimbra-3000-548, Portugal"},{"name":"Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), University of Coimbra, Coimbra-3000-548, Portugal"}]},{"given":"T\u00e2nia","family":"Martins-Marques","sequence":"additional","affiliation":[{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3004\u2013504 Coimbra, Portugal"}]},{"given":"Magda","family":"Silva","sequence":"additional","affiliation":[{"name":"ICNAS \u2013 Institute for Nuclear Sciences Applied to Health; University of Coimbra, Coimbra-3000-548, Portugal"},{"name":"Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), University of Coimbra, Coimbra-3000-548, Portugal"},{"name":"Institute for Nuclear Sciences Applied to Health (ICNAS Pharma), Polo das Ci\u00eancias da Sa\u00fade, University of Coimbra, 3000-548 Coimbra, Portugal"}]},{"given":"Maria Jo\u00e3o","family":"Ferreira","sequence":"additional","affiliation":[{"name":"ICNAS \u2013 Institute for Nuclear Sciences Applied to Health; University of Coimbra, Coimbra-3000-548, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3004\u2013504 Coimbra, Portugal"},{"name":"Cardiology Department, Centro Hospitalar e Universit\u00e1rio de Coimbra, Praceta Prof. Mota Pinto, 3000-075, Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5786-8447","authenticated-orcid":false,"given":"Henrique","family":"Girao","sequence":"additional","affiliation":[{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3004\u2013504 Coimbra, Portugal"}]},{"given":"Antero","family":"Abrunhosa","sequence":"additional","affiliation":[{"name":"ICNAS \u2013 Institute for Nuclear Sciences Applied to Health; 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