{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T05:21:11Z","timestamp":1791523271724,"version":"4.3.4"},"reference-count":48,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2022,6,28]],"date-time":"2022-06-28T00:00:00Z","timestamp":1656374400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health"},{"name":"Legnaro National Laboratories of the Italian Institute of Nuclear Physics"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Copper radioisotopes are generally employed for cancer imaging and therapy when firmly coordinated via a chelating agent coupled to a tumor-seeking vector. However, the biologically triggered Cu2+-Cu+ redox switching may constrain the in vivo integrity of the resulting complex, leading to demetallation processes. This unsought pathway is expected to be hindered by chelators bearing N, O, and S donors which appropriately complements the borderline-hard and soft nature of Cu2+ and Cu+. In this work, the labelling performances of a series of S-rich polyazamacrocyclic chelators with [64Cu]Cu2+ and the stability of the [64Cu]Cu-complexes thereof were evaluated. Among the chelators considered, the best results were obtained with 1,7-bis [2-(methylsulfanyl)ethyl]-4,10,diacetic acid-1,4,7,10-tetraazacyclododecane (DO2A2S). DO2A2S was labelled at high molar activities in mild reaction conditions, and its [64Cu]Cu2+ complex showed excellent integrity in human serum over 24 h. Biodistribution studies in BALB\/c nude mice performed with [64Cu][Cu(DO2A2S)] revealed a behavior similar to other [64Cu]Cu-labelled cyclen derivatives characterized by high liver and kidney uptake, which could either be ascribed to transchelation phenomena or metabolic processing of the intact complex.<\/jats:p>","DOI":"10.3390\/molecules27134158","type":"journal-article","created":{"date-parts":[[2022,6,29]],"date-time":"2022-06-29T01:48:38Z","timestamp":1656467318000},"page":"4158","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Chelation of Theranostic Copper Radioisotopes with S-Rich Macrocycles: From Radiolabelling of Copper-64 to In Vivo Investigation"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3726-6174","authenticated-orcid":false,"given":"Marianna","family":"Tosato","sequence":"first","affiliation":[{"name":"Department of Chemical Sciences, University of Padova, Via Marzolo 1, 35131 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Verona","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Padova, Via Marzolo 8, 35131 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2096-8994","authenticated-orcid":false,"given":"Chiara","family":"Favaretto","sequence":"additional","affiliation":[{"name":"Center for Radiopharmaceutical Sciences, Paul Scherrer Institute, 5232 Villigen, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Pometti","sequence":"additional","affiliation":[{"name":"Nuclear Medicine Department, Cannizzaro Hospital, Via Messina 829, 95126 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1380-1248","authenticated-orcid":false,"given":"Giordano","family":"Zanoni","sequence":"additional","affiliation":[{"name":"Department of Chemical Sciences, University of Padova, Via Marzolo 1, 35131 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizio","family":"Scopelliti","sequence":"additional","affiliation":[{"name":"Nuclear Medicine Department, Cannizzaro Hospital, Via Messina 829, 95126 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0554-6649","authenticated-orcid":false,"given":"Francesco Paolo","family":"Cammarata","sequence":"additional","affiliation":[{"name":"Institute of Molecular Bioimaging and Physiology, National Research Council (IBFM-CNR), 90015 Cefal\u00f9, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Morselli","sequence":"additional","affiliation":[{"name":"Legnaro National Laboratories, Italian Institute of Nuclear Physics, Viale Dell\u2019Universit\u00e0 2, 35020 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5095-799X","authenticated-orcid":false,"given":"Zeynep","family":"Talip","sequence":"additional","affiliation":[{"name":"Center for Radiopharmaceutical Sciences, Paul Scherrer Institute, 5232 Villigen, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6077-5594","authenticated-orcid":false,"given":"Nicholas P.","family":"van der Meulen","sequence":"additional","affiliation":[{"name":"Center for Radiopharmaceutical Sciences, Paul Scherrer Institute, 5232 Villigen, Switzerland"},{"name":"Laboratory of Radiochemistry, Paul Scherrer Institute, 5232 Villigen, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6108-746X","authenticated-orcid":false,"given":"Valerio","family":"Di Marco","sequence":"additional","affiliation":[{"name":"Department of Chemical Sciences, University of Padova, Via Marzolo 1, 35131 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mattia","family":"Asti","sequence":"additional","affiliation":[{"name":"Radiopharmaceutical Chemistry Section, Nuclear Medicine Unit, AUSL-IRCCS di Reggio Emilia, Via Amendola 2, 42122 Reggio Emilia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"11530","DOI":"10.1021\/acs.inorgchem.1c01550","article-title":"Copper Coordination Chemistry of Sulfur Pendant Cyclen Derivatives: An Attempt to Hinder the Reductive-Induced Demetallation in 64\/67Cu Radiopharmaceuticals","volume":"60","author":"Tosato","year":"2021","journal-title":"Inorg. 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