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Manganese-52 (<jats:sup>52<\/jats:sup>Mn, t<jats:sub>1\/2<\/jats:sub>\u2009=\u20095.6 d, \u03b2<jats:sup>+<\/jats:sup> \u2009=\u200929.6%, E(\u03b2<jats:sub>ave<\/jats:sub>)\u2009=\u2009242\u00a0keV) is suitable for imaging at longer time points providing a complementary technique to Zirconium-89 (<jats:sup>89<\/jats:sup>Zr, t<jats:sub>1\/2<\/jats:sub>\u2009=\u20093.3 d, \u03b2<jats:sup>+<\/jats:sup> \u2009=\u200922.7%, E(\u03b2<jats:sub>ave<\/jats:sub>)\u2009=\u2009396\u00a0keV)) because of its long half-life and low positron energy. To exploit these properties, we aimed to investigate suitable bifunctional chelators that could be readily conjugated to antibodies and labeled with <jats:sup>52<\/jats:sup>Mn under mild conditions using trastuzumab as a proof-of-concept.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Procedures<\/jats:title>\n                <jats:p>Trastuzumab was incubated with S-2-(4-isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane tetraacetic acid (p-SCN-Bn-DOTA), 1-Oxa-4,7,10-tetraazacyclododecane-5-S-(4-isothiocyantobenzyl)-4,7,10-triacetic acid (p-SCN-Bn-Oxo-DO3A), and 3,6,9,15-tetraazabicyclo[9.3.1] pentadeca-1(15),11,13-triene-4-S-(4-isothiocyanatobenzyl)-3,6,9-triacetic acid (p-SCN-Bn-PCTA) at a tenfold molar excess. The immunoconjugates were purified, combined with [<jats:sup>52<\/jats:sup>Mn]MnCl<jats:sub>2<\/jats:sub> at different ratios, and the labeling efficiency was assessed by iTLC. The immunoreactive fraction of the radiocomplex was determined through a Lindmo assay. Cell studies were conducted in HER2\u2009+\u2009(BT474) and HER2- (MDA-MB-468) cell lines followed by <jats:italic>in vivo<\/jats:italic> studies.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Trastuzumab-Oxo-DO3A was labeled within 30\u00a0min at 37\u00a0\u00b0C with a radiochemical yield (RCY) of 90\u2009\u00b1\u20091.5% and with the highest specific activity of the chelators investigated of 16.64\u00a0MBq\/nmol. The labeled compound was purified with a resulting radiochemical purity of\u2009&gt;\u200998% and retained a 67\u2009\u00b1\u20091.2% immunoreactivity. DOTA and PCTA immunoconjugates resulted in\u2009&lt;\u200950\u2009\u00b1\u20092.5% (RCY) with similar specific activity. Mouse serum stability studies of [<jats:sup>52<\/jats:sup>Mn]Mn-Oxo-DO3A-trastuzumab showed 95% intact complex for over 5\u00a0days. Cell uptake studies showed higher uptake in HER2\u2009+\u2009(12.51\u2009\u00b1\u20090.83% \/mg) cells compared to HER2- (0.85\u2009\u00b1\u20090.10%\/mg) cells. PET images of mice bearing BT474 tumors showed high tumor uptake that was consistent with the biodistribution (42.02\u2009\u00b1\u20092.16%ID\/g, 14 d) compared to MDA-MB-468 tumors (2.20\u2009\u00b1\u20090.80%ID\/g, 14 d). Additionally, both models exhibited low bone uptake of\u2009&lt;\u20091% ID\/g.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>The bifunctional chelator p-SCN-Bn-Oxo-DO3A is promising for the development of <jats:sup>52<\/jats:sup>Mn radiopharmaceuticals as it was easily conjugated, radiolabeled at mild conditions, and illustrated stability for a prolonged duration both <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>. High-quality PET\/CT images of [<jats:sup>52<\/jats:sup>Mn]Mn-Oxo-DO3A-trastuzumab were obtained 14 d post-injection. This study illustrates the potential of [<jats:sup>52<\/jats:sup>Mn]Mn-Oxo-DO3A for the evaluation of antibodies using PET imaging.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s11307-024-01948-4","type":"journal-article","created":{"date-parts":[[2024,8,27]],"date-time":"2024-08-27T17:02:36Z","timestamp":1724778156000},"page":"858-868","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Development of 52Mn Labeled Trastuzumab for Extended Time Point PET Imaging of HER2"],"prefix":"10.1007","volume":"26","author":[{"given":"James M.","family":"Omweri","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shefali","family":"Saini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hailey A.","family":"Houson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Volkan","family":"Tekin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer M.","family":"Pyles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Candace C.","family":"Parker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0090-0191","authenticated-orcid":false,"given":"Suzanne E.","family":"Lapi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,8,27]]},"reference":[{"issue":"1","key":"1948_CR1","doi-asserted-by":"publisher","first-page":"57","DOI":"10.3390\/ijms18010057","volume":"18","author":"C Bailly","year":"2016","unstructured":"Bailly C, Clery PF, Faivre-Chauvet A et al (2016) Immuno-PET for Clinical Theranostic Approaches. 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