{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T07:50:40Z","timestamp":1767858640901,"version":"3.49.0"},"reference-count":29,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,6,9]],"date-time":"2023-06-09T00:00:00Z","timestamp":1686268800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"PORTUGUESE FOUNDATION FOR SCIENCE AND TECHNOLOGY (FCT)","award":["ERANET- EURONANOMED-3-I2PAD"],"award-info":[{"award-number":["ERANET- EURONANOMED-3-I2PAD"]}]},{"name":"PORTUGUESE FOUNDATION FOR SCIENCE AND TECHNOLOGY (FCT)","award":["PD\/BDE\/150331\/2019"],"award-info":[{"award-number":["PD\/BDE\/150331\/2019"]}]},{"name":"PORTUGUESE FOUNDATION FOR SCIENCE AND TECHNOLOGY (FCT)","award":["PD\/BDE\/150681\/2020"],"award-info":[{"award-number":["PD\/BDE\/150681\/2020"]}]},{"name":"Unitatea Executiva Pentru Finantarea Invatamantului Superior, a Cercetarii, Dezvoltarii si Inovarii","award":["ERANET- EURONANOMED-3-I2PAD"],"award-info":[{"award-number":["ERANET- EURONANOMED-3-I2PAD"]}]},{"name":"Unitatea Executiva Pentru Finantarea Invatamantului Superior, a Cercetarii, Dezvoltarii si Inovarii","award":["PD\/BDE\/150331\/2019"],"award-info":[{"award-number":["PD\/BDE\/150331\/2019"]}]},{"name":"Unitatea Executiva Pentru Finantarea Invatamantului Superior, a Cercetarii, Dezvoltarii si Inovarii","award":["PD\/BDE\/150681\/2020"],"award-info":[{"award-number":["PD\/BDE\/150681\/2020"]}]},{"DOI":"10.13039\/501100001871","name":"FCT","doi-asserted-by":"publisher","award":["ERANET- EURONANOMED-3-I2PAD"],"award-info":[{"award-number":["ERANET- EURONANOMED-3-I2PAD"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"FCT","doi-asserted-by":"publisher","award":["PD\/BDE\/150331\/2019"],"award-info":[{"award-number":["PD\/BDE\/150331\/2019"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"FCT","doi-asserted-by":"publisher","award":["PD\/BDE\/150681\/2020"],"award-info":[{"award-number":["PD\/BDE\/150681\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"name":"IOSIN program of the Romanian Ministry of Research, Innovation and Digitization","award":["ERANET- EURONANOMED-3-I2PAD"],"award-info":[{"award-number":["ERANET- EURONANOMED-3-I2PAD"]}]},{"name":"IOSIN program of the Romanian Ministry of Research, Innovation and Digitization","award":["PD\/BDE\/150331\/2019"],"award-info":[{"award-number":["PD\/BDE\/150331\/2019"]}]},{"name":"IOSIN program of the Romanian Ministry of Research, Innovation and Digitization","award":["PD\/BDE\/150681\/2020"],"award-info":[{"award-number":["PD\/BDE\/150681\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Antibody and nanobody-based copper-64 radiopharmaceuticals are increasingly being proposed as theranostic tools in multiple human diseases. While the production of copper-64 using solid targets has been established for many years, its use is limited due to the complexity of solid target systems, which are available in only a few cyclotrons worldwide. In contrast, liquid targets, available in virtually in all cyclotrons, constitute a practical and reliable alternative. In this study, we discuss the production, purification, and radiolabeling of antibodies and nanobodies using copper-64 obtained from both solid and liquid targets. Copper-64 production from solid targets was performed on a TR-19 cyclotron with an energy of 11.7 MeV, while liquid target production was obtained by bombarding a nickel-64 solution using an IBA Cyclone Kiube cyclotron with 16.9 MeV on target. Copper-64 was purified from both solid and liquid targets and used to radiolabel NODAGA-Nb, NOTA-Nb, and DOTA-Trastuzumab conjugates. Stability studies were conducted on all radioimmunoconjugates in mouse serum, PBS, and DTPA. Irradiation of the solid target yielded 13.5 \u00b1 0.5 GBq with a beam current of 25 \u00b1 1.2 \u03bcA and an irradiation time of 6 h. On the other hand, irradiation of the liquid target resulted in 2.8 \u00b1 1.3 GBq at the end of bombardment (EOB) with a beam current of 54.5 \u00b1 7.8 \u03bcA and an irradiation time of 4.1 \u00b1 1.3 h. Successful radiolabeling of NODAGA-Nb, NOTA-Nb, and DOTA-Trastuzumab with copper-64 from both solid and liquid targets was achieved. Specific activities (SA) obtained with the solid target were 0.11, 0.19, and 0.33 MBq\/\u03bcg for NODAGA-Nb, NOTA-Nb, and DOTA-trastuzumab, respectively. For the liquid target, the corresponding SA values were 0.15, 0.12, and 0.30 MBq\/\u03bcg. Furthermore, all three radiopharmaceuticals demonstrated stability under the testing conditions. While solid targets have the potential to produce significantly higher activity in a single run, the liquid process offers advantages such as speed, ease of automation, and the feasibility of back-to-back production using a medical cyclotron. In this study, successful radiolabeling of antibodies and nanobodies was achieved using both solid and liquid targets approaches. The radiolabeled compounds exhibited high radiochemical purity and specific activity, rendering them suitable for subsequent in vivo pre-clinical imaging studies.<\/jats:p>","DOI":"10.3390\/molecules28124670","type":"journal-article","created":{"date-parts":[[2023,6,9]],"date-time":"2023-06-09T08:37:33Z","timestamp":1686299853000},"page":"4670","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Antibody and Nanobody Radiolabeling with Copper-64: Solid vs. Liquid Target Approach"],"prefix":"10.3390","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1671-7861","authenticated-orcid":false,"given":"Ivanna","family":"Hrynchak","sequence":"first","affiliation":[{"name":"Institute for Nuclear Sciences Applied to Health (ICNAS Pharma), Polo das Ci\u00eancias da Sa\u00fade, University of Coimbra, 3000-548 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0445-0581","authenticated-orcid":false,"given":"Diana","family":"Cocioab\u0103","sequence":"additional","affiliation":[{"name":"Horia Hulubei National Institute for Physics and Nuclear Engineering (IFIN-HH), Radiopharmaceutical Research Centre, 077125 M\u0103gurele, Romania"},{"name":"Faculty of Physics, Doctoral School of Physics, University of Bucharest, 077125 Bucharest, Romania"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1924-178X","authenticated-orcid":false,"given":"Alexandra I.","family":"Fonseca","sequence":"additional","affiliation":[{"name":"Institute for Nuclear Sciences Applied to Health (ICNAS Pharma), Polo das Ci\u00eancias da Sa\u00fade, University of Coimbra, 3000-548 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2929-8280","authenticated-orcid":false,"given":"Radu","family":"Leonte","sequence":"additional","affiliation":[{"name":"Horia Hulubei National Institute for Physics and Nuclear Engineering (IFIN-HH), Radiopharmaceutical Research Centre, 077125 M\u0103gurele, Romania"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4631-7268","authenticated-orcid":false,"given":"S\u00e9rgio J. C.","family":"do Carmo","sequence":"additional","affiliation":[{"name":"Institute for Nuclear Sciences Applied to Health (ICNAS Pharma), Polo das Ci\u00eancias da Sa\u00fade, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Institute for Nuclear Sciences Applied to Health (ICNAS), University of Coimbra, 3000-548 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7886-9900","authenticated-orcid":false,"given":"Roxana","family":"Cornoiu","sequence":"additional","affiliation":[{"name":"Horia Hulubei National Institute for Physics and Nuclear Engineering (IFIN-HH), Radiopharmaceutical Research Centre, 077125 M\u0103gurele, Romania"},{"name":"Faculty of Chemical Engineering and Biotechnologies, Doctoral School of Applied Chemistry and Materials Science, University Politehnica of Bucharest, 011061 Bucharest, Romania"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3854-6549","authenticated-orcid":false,"given":"Am\u00edlcar","family":"Falc\u00e3o","sequence":"additional","affiliation":[{"name":"Institute for Nuclear Sciences Applied to Health (ICNAS Pharma), Polo das Ci\u00eancias da Sa\u00fade, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4769-843X","authenticated-orcid":false,"given":"Dana","family":"Niculae","sequence":"additional","affiliation":[{"name":"Horia Hulubei National Institute for Physics and Nuclear Engineering (IFIN-HH), Radiopharmaceutical Research Centre, 077125 M\u0103gurele, Romania"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4145-854X","authenticated-orcid":false,"given":"Antero J.","family":"Abrunhosa","sequence":"additional","affiliation":[{"name":"Institute for Nuclear Sciences Applied to Health (ICNAS Pharma), Polo das Ci\u00eancias da Sa\u00fade, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Institute for Nuclear Sciences Applied to Health (ICNAS), University of Coimbra, 3000-548 Coimbra, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1063\/1.4773946","article-title":"Routine production of copper-64 using 11.7MeV protons","volume":"1509","author":"Jeffery","year":"2012","journal-title":"AIP Conf. 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