Stapled peptide-based radiotheranostics for intracellular protein-protein interactions targeted cancer imaging and therapy

本研究项目旨在发展以钉接肽为基础的靶向细胞内蛋白相互作用的放射治疗。在过去的财政年度，我开发了一种基于钉接肽的64Cu标记放射治疗药物，它可以特异性地与各种癌细胞中的hDM2结合。放射肿瘤学[64Cu]STP08在几种动物模型中显示出高度的肿瘤积聚和滞留。更重要的是，在小鼠模型中，它显著延缓了肿瘤的生长，其疗效与p53表型无关。生物安全性研究表明，[64Cu]STP08在正常小鼠中表现良好，未引起血液学和器官病变。此外，我们还成功地用225Ac（一种发射放射性核素的α粒子）标记了STP。[225Ac]STP08具有良好的治疗效果。

This research project aims at the development of stapled peptide-based radiotheranostics for targeting intracellular protein protein interactions. In the past fiscal year, I developed a stapled peptide based, 64Cu labeled radiotheranostics, which can specifically bind to hDM2 in various cancer cells. The radiotheranostics, [64Cu]STP08, showed high tumor accumulation and retention in several animal models.More importantly, it significantly delayed tumor growth in mouse models and the efficacy is independent to the p53 phenotype.Biosafety study suggested that [64Cu]STP08 showed satisfactory and caused no hemotological and organ lesions in normal mice.Moreover, we have successfully labelled STP with 225Ac, an alpha particle emitting radionuclide. The [225Ac]STP08 showed excellent treatment efficacy.