在过去的二十年里，内皮素（ET）轴在癌症中的新兴作用已得到广泛研究，其参与的几种被称为“癌症标志”的机制清楚地凸显了其作为治疗靶点的潜力。尽管人们对寻找有效的抗癌药物越来越感兴趣，但尚未有突破性的治疗方法成功进入市场。最近，我们的团队报道了一种针对ETA受体（ETA，ET受体之一）的新型免疫正电子发射断层扫描探针的开发，可以成功检测ETA胶质母细胞瘤，为新型基于抗体的药物的开发铺平了道路。策略。在这项研究中，我们描述了两种 PET/NIRF（正电子发射断层扫描/近红外荧光）双功能成像剂的合成，针对 ETA 或 ETB，可用于检测 ET 肿瘤并选择有资格接受治疗的患者。荧光引导手术。使用具有 IRDye800CW 荧光团和用于 89Zr 螯合的去铁胺的高度通用的四嗪平台将两种成像模式结合在一起。然后，通过逆电子需求狄尔斯-阿尔德反应，将这种所谓的单分子多模态成像探针“点击”到与反式环辛烯基团特异性结合的抗体上。这种方法产生了同质且明确的构建体，这些构建体保留了对各自靶标的高亲和力和高特异性，如流式细胞术和 NIRF 体内成像实验在携带 CHO-ETA 和 CHO-ETB 肿瘤的裸鼠中所显示的那样。最终，这些双模式免疫偶联物可用于改善 ET 肿瘤患者的预后。

For the past two decades, the emerging role of the endothelin (ET) axis in cancer has been extensively investigated, and its involvement in several mechanisms described as "hallmarks of cancer" has clearly highlighted its potential as a therapeutic target. Despite the growing interest in finding effective anticancer drugs, no breakthrough treatment has successfully made its way to the market. Recently, our team reported the development of a new immuno-positron emission tomography probe targeting the ET A receptor (ETA, one of the ET receptors) that allows the successful detection of ETA+ glioblastoma, paving the way for the elaboration of novel antibody-based strategies. In this study, we describe the synthesis of two PET/NIRF (positron emission tomography/near-infrared fluorescence) dually functionalized imaging agents, directed against ETA or ETB, that could be used to detect ET+ tumors and select patients that will be eligible for fluorescence-guided surgery. Both imaging modalities were brought together using a highly versatile tetrazine platform bearing the IRDye800CW fluorophore and desferrioxamine for 89Zr chelation. This so-called monomolecular multimodal imaging probe was then "clicked", via an inverse-electron-demand Diels-Alder reaction, to antibodies conjugated site-specifically with a trans-cyclooctene group. This approach has led to homogeneous and well-defined constructs that retained their high affinity and high specificity for their respective target, as shown by flow cytometry and NIRF in vivo imaging experiments in nude mice bearing CHO-ETA and CHO-ETB tumors. Ultimately, these bimodal immunoconjugates could be used to improve the outcomes of patients with ET+ tumors.