最近开发的代谢更稳定的小胃泌素衍生物 DOTA-CCK-66 在用 68Ga 或 177Lu 标记时显示出有希望的临床前数据。使用 [68Ga]Ga-DOTA-CCK-66 对两名甲状腺髓样癌 (MTC) 患者进行的首次正电子发射断层扫描/计算机断层扫描 (PET/CT) 成像显示出良好的生物分布特征。在这里，我们的目的是在 [177Lu]Lu- 与 [225Ac]Ac-DOTA-CCK 的比较治疗研究中研究 [225Ac]Ac-DOTA-CCK-66 作为靶向 α 治疗 (TAT) 药物的治疗潜力-66.进行治疗研究（3组，n = 5，AR42J荷瘤394-NOD SCID小鼠）。对照组动物注射 [68Ga]Ga-DOTA-CCK-66（1.1 MBq，PET/CT 成像），而治疗组动物注射单剂量 [177Lu]Lu-DOTA-CCK-66（37 MBq，放射配体治疗 (RLT)) 或 [225Ac]Ac-DOTA-CCK-66 (37 kBq, TAT)。每周两次监测所有动物的肿瘤体积和体重，直至达到终点标准。处死小鼠后，对血样进行评估（VetScan VS2，Abaxis）。治疗后，观察到治疗组的肿瘤体积最初下降，随后肿瘤生长显着延迟。与未处理的动物 (12±±3 天) 相比，177Lu 和 225Ac 处理的动物的平均存活率分别增加了 3 倍 (37±3 天) 和 4.5 倍 (54±6 天)。血样分析未表明 177Lu 和 225Ac 治疗后对肝脏、肾脏或胃有毒副作用。我们证明了 177Lu 和 225Ac 标记的 DOTA-CCK-66 具有显着的治疗功效。正如预期的那样，后者的治疗导致了最高的平均存活率。这些结果表明 225Ac 标记的 DOTA-CCK-66 在 MTC 患者管理中对 TAT 具有很高的治疗潜力。© 2024。作者。

The recently developed metabolically more stable minigastrin derivative, DOTA-CCK-66, displayed promising preclinical data when labeled either with 68Ga or 177Lu. First positron emission tomography/computed tomography (PET/CT) imaging using [68Ga]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 [225Ac]Ac-DOTA-CCK-66 as a targeted α-therapy (TAT) agent in a comparative treatment study of [177Lu]Lu- versus [225Ac]Ac-DOTA-CCK-66.Treatment studies were performed (3 groups, n = 5, AR42J tumor-bearing 394-NOD SCID mice). Control group animals were injected with [68Ga]Ga-DOTA-CCK-66 (1.1 MBq, PET/CT imaging), while treatment group animals received a single dose of either [177Lu]Lu-DOTA-CCK-66 (37 MBq, radioligand therapy (RLT)) or [225Ac]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.Upon treatment, an initial decline in tumor volume, followed by a significantly delayed tumor growth of treated cohorts, was observed. Mean survival of 177Lu- as well as 225Ac-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 177Lu and 225Ac-treatment.We demonstrated a substantial therapeutic efficacy of 177Lu- and 225Ac-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 225Ac-labeled DOTA-CCK-66 for TAT in MTC patient management.© 2024. The Author(s).