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First positron emission tomography\/computed tomography (PET\/CT) imaging using [\n                      <jats:sup>68<\/jats:sup>\n                      Ga]Ga-DOTA-CCK-66 in two patients suffering from medullary thyroid carcinoma (MTC) displayed a favorable biodistribution profile. Here, we aim to investigate the therapeutic potential of [\n                      <jats:sup>225<\/jats:sup>\n                      Ac]Ac-DOTA-CCK-66 as a targeted \u03b1-therapy (TAT) agent in a comparative treatment study of [\n                      <jats:sup>177<\/jats:sup>\n                      Lu]Lu- versus [\n                      <jats:sup>225<\/jats:sup>\n                      Ac]Ac-DOTA-CCK-66.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Treatment studies were performed (3 groups, n\u2009=\u20095, AR42J tumor-bearing 394-NOD SCID mice). Control group animals were injected with [\n                      <jats:sup>68<\/jats:sup>\n                      Ga]Ga-DOTA-CCK-66 (1.1\u00a0MBq, PET\/CT imaging), while treatment group animals received a single dose of either [\n                      <jats:sup>177<\/jats:sup>\n                      Lu]Lu-DOTA-CCK-66 (37\u00a0MBq, radioligand therapy (RLT)) or [\n                      <jats:sup>225<\/jats:sup>\n                      Ac]Ac-DOTA-CCK-66 (37\u00a0kBq, TAT). All animals' tumor volume and body weight were monitored twice a week until end-point criteria were reached. Blood samples were evaluated (VetScan VS2, Abaxis) once mice were sacrificed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Upon treatment, an initial decline in tumor volume, followed by a significantly delayed tumor growth of treated cohorts, was observed. Mean survival of\n                      <jats:sup>177<\/jats:sup>\n                      Lu- as well as\n                      <jats:sup>225<\/jats:sup>\n                      Ac-treated animals was increased by 3- (37\u2009\u00b1\u20093 d) and 4.5-fold (54\u2009\u00b1\u20096\u00a0d), respectively, when compared to non-treated animals (12\u2009\u00b1\u20093\u00a0d). Blood sample analysis did not indicate toxic side effects to the liver, kidney, or stomach upon\n                      <jats:sup>177<\/jats:sup>\n                      Lu and\n                      <jats:sup>225<\/jats:sup>\n                      Ac-treatment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      We demonstrated a substantial therapeutic efficacy of\n                      <jats:sup>177<\/jats:sup>\n                      Lu- and\n                      <jats:sup>225<\/jats:sup>\n                      Ac-labeled DOTA-CCK-66. As expected, treatment with the latter resulted in the highest mean survival rates. These results indicate a high therapeutic potential of\n                      <jats:sup>225<\/jats:sup>\n                      Ac-labeled DOTA-CCK-66 for TAT in MTC patient management.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Graphical abstract<\/jats:title>\n                  <\/jats:sec>","DOI":"10.1007\/s00259-024-06927-z","type":"journal-article","created":{"date-parts":[[2024,10,11]],"date-time":"2024-10-11T01:01:54Z","timestamp":1728608514000},"page":"458-468","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Preclinical evaluation of 225Ac-labeled minigastrin analog DOTA-CCK-66 for Targeted Alpha Therapy"],"prefix":"10.1007","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8258-3526","authenticated-orcid":false,"given":"Nadine","family":"Holzleitner","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meryl","family":"Vilangattil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abir","family":"Swaidan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara Diaz","family":"Garcia-Prada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco F.","family":"Taddio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pauline","family":"Jeanjean","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine E.","family":"Mona","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constantin","family":"Lapa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Casini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"G\u00fcnther","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7494-335X","authenticated-orcid":false,"given":"Giuseppe","family":"Carlucci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,10,11]]},"reference":[{"key":"6927_CR1","doi-asserted-by":"publisher","unstructured":"Hennrich U, Kopka K. 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