胰腺导管腺癌（PDAC）仍然是一种临床需求未满足的恶性肿瘤。开发以靶向癌症特异性受体为基础的放射免疫偶联物提供了对PDAC的转移性和原发性放射免疫治疗的机会。在本研究中，我们对一种新型的β放射性免疫偶联物[177Lu]Lu-DOTA-C595在PDAC治疗上的体外行为进行了表征。[177Lu]Lu-DOTA-C595被设计用于靶向癌症特异性粘蛋白1（MUC1-CE）表位，在大多数上皮性癌症，包括PDAC上过度表达。我们对展示出不同强度MUC1-CE表达的PDAC细胞系（PANC-1、CAPAN-1、BxPC-3和AsPC-1）进行了一系列的体外实验。[177Lu]Lu-DOTA-C595与所有细胞系结合，与其MUC1-CE的表达相关。[177Lu]Lu-DOTA-C595也被迅速内化到所有细胞系中，在48小时内PANC-1细胞系内化活性的最大值达到75.4%。根据PANC-1和AsPC-1细胞系在暴露于[177Lu]Lu-DOTA-C595后γH2AX斑点的表达和克隆生存情况，用于量化[177Lu]Lu-DOTA-C595在体外细胞毒性。在治疗后1小时，两种细胞系中γH2AX斑点的表达均超过97％。在PANC-1细胞中，γH2AX斑点的表达在24小时内继续增加，而在AsPC-1细胞中减少。克隆生成活性实验显示[177Lu]Lu-DOTA-C595诱导了高水平的细胞杀伤。[177Lu]Lu-DOTA-C595在体外具有有利的特点，可以靶向和治疗MUC1-CE阳性的PDAC。有必要进一步研究[177Lu]Lu-DOTA-C595在其他表达MUC1-CE的恶性肿瘤，如肺癌、卵巢癌和结直肠腺癌中的体内效果和潜在价值。© 2023. Springer Nature Switzerland AG.

Pancreatic ductal adenocarcinoma (PDAC) continues to be a malignancy with an unmet clinical demand. Development of radioimmunoconjugates which target cancer-specific receptors provides an opportunity for radioimmunotherapy of both metastatic and primary PDAC. In this study, we characterised the in vitro behaviour of a novel beta-emitting radioimmunoconjugate [177Lu]Lu-DOTA-C595 as a therapeutic agent against PDAC. [177Lu]Lu-DOTA-C595 is designed to target cancer-specific mucin 1 epitopes (MUC1-CE) overexpressed on most epithelial cancers, including PDAC.A series of in vitro experiments were performed on PDAC cell lines (PANC-1, CAPAN-1, BxPC-3 and AsPC-1) exhibiting strong to weak MUC1-CE expression. [177Lu]Lu-DOTA-C595 bound to all cell lines relative to their expression of MUC1-CE. [177Lu]Lu-DOTA-C595 was also rapidly internalised across all cell lines, with a maximum of 75.4% of activity internalised within the PANC-1 cell line at 48 h. The expression of γH2AX foci and clonogenic survival of PANC-1 and AsPC-1 cell lines after exposure to [177Lu]Lu-DOTA-C595 were used to quantify the in vitro cytotoxicity of [177Lu]Lu-DOTA-C595. At 1 h post treatment, the expression of γH2AX foci exceeded 97% in both cell lines. The expression of γH2AX foci continued to increase in PANC-1 cells at 24 h, although expression reduced in AsPC-1. Clonogenic assays showed a high level of cell kill induced by [177Lu]Lu-DOTA-C595.[177Lu]Lu-DOTA-C595 has favourable in vitro characteristics to target and treat MUC1-CE positive PDAC. Further investigations to characterise the in vivo effects and potential value of [177Lu]Lu-DOTA-C595 in other MUC1-CE expressing malignancies such as lung, ovarian and colorectal adenocarcinoma are warranted.© 2023. Springer Nature Switzerland AG.