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Abstract/Summary
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<jats:sec>
<jats:title>Abstract</jats:title>
<jats:p>The recently developed metabolically more stable minigastrin derivative, DOTA-CCK-66, displayed promising preclinical data when labeled either with <jats:sup>68</jats:sup>Ga or <jats:sup>177</jats:sup>Lu. First positron emission tomography/computed tomography (PET/CT) imaging using [<jats:sup>68</jats:sup>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 [<jats:sup>225</jats:sup>Ac]Ac-DOTA-CCK-66 as a targeted α-therapy (TAT) agent in a comparative treatment study of [<jats:sup>177</jats:sup>Lu]Lu- versus [<jats:sup>225</jats:sup>Ac]Ac-DOTA-CCK-66.</jats:p>
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<jats:title>Methods</jats:title>
<jats:p>Treatment studies were performed (3 groups, n = 5, AR42J tumor-bearing 394-NOD SCID mice). Control group animals were injected with [<jats:sup>68</jats:sup>Ga]Ga-DOTA-CCK-66 (1.1 MBq, PET/CT imaging), while treatment group animals received a single dose of either [<jats:sup>177</jats:sup>Lu]Lu-DOTA-CCK-66 (37 MBq, radioligand therapy (RLT)) or [<jats:sup>225</jats:sup>Ac]Ac-DOTA-CCK-66 (37 kBq, 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.</jats:p>
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<jats:title>Results</jats:title>
<jats:p>Upon treatment, an initial decline in tumor volume, followed by a significantly delayed tumor growth of treated cohorts, was observed. Mean survival of <jats:sup>177</jats:sup>Lu- as well as <jats:sup>225</jats:sup>Ac-treated animals was increased by 3- (37 ± 3 d) and 4.5-fold (54 ± 6 d), respectively, when compared to non-treated animals (12 ± 3 d). Blood sample analysis did not indicate toxic side effects to the liver, kidney, or stomach upon <jats:sup>177</jats:sup>Lu and <jats:sup>225</jats:sup>Ac-treatment.</jats:p>
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<jats:title>Conclusion</jats:title>
<jats:p>We demonstrated a substantial therapeutic efficacy of <jats:sup>177</jats:sup>Lu- and <jats:sup>225</jats:sup>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 <jats:sup>225</jats:sup>Ac-labeled DOTA-CCK-66 for TAT in MTC patient management.</jats:p>
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<jats:sec>
<jats:title>Graphical abstract</jats:title>
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Hinweis
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DeepGreen-ID: 423eddd839d84ac0952f64574b2d31b1 ; metadata provieded by: DeepGreen (https://www.oa-deepgreen.de/api/v1/), LIVIVO search scope life sciences (http://z3950.zbmed.de:6210/livivo), Crossref Unified Resource API (https://api.crossref.org/swagger-ui/index.html), to.science.api (https://frl.publisso.de/), ZDB JSON-API (beta) (https://zeitschriftendatenbank.de/api/), lobid - Dateninfrastruktur für Bibliotheken (https://lobid.org/resources/search)
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