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

基于钉合肽的放射治疗用于细胞内蛋白质-蛋白质相互作用靶向癌症成像和治疗

• 批准号: 21H02873
• 负责人: 胡 寛
• 金额: $ 10.65万
• 依托单位: National Institutes for Quantum Science and Technology
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2021
• 资助国家: 日本
• 起止时间: 2021-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-21H02873/
• 关键词: stapled peptide; radiotheranostics; intracellular protein; cancer; 64Cu; radionuclide therapy; intracellular delivery; PET imaging

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.

该研究项目旨在开发基于钉合肽的放射治疗，用于靶向细胞内蛋白质相互作用。在上一财年，我开发了一种基于钉合肽的 64Cu 标记放射治疗剂，它可以与各种癌细胞中的 hDM2 特异性结合。放射治疗剂[64Cu]STP08在多种动物模型中表现出高肿瘤积累和保留。更重要的是，它在小鼠模型中显着延迟肿瘤生长，并且疗效与p53表型无关。生物安全研究表明[64Cu]STP08表现出令人满意的效果并且对正常小鼠没有造成血液学和器官损伤。此外，我们成功地用225Ac（一种发射α粒子的放射性核素）标记STP。 [225Ac]STP08显示出优异的治疗效果。

项目成果

Development of a stable peptide-based PET tracer for detecting CD133-expressing cancer stem cells

开发基于肽的稳定 PET 示踪剂，用于检测表达 CD133 的癌症干细胞

• 发表时间: 2021
• 作者: Hu Kuan ;Xie Lin ;Yiding Zhang ;Hanyu Masayuki ;Obata Honoka ;Nagatsu Kotaro ;Suzuki Hisashi ;Zhang Ming-Rong
• 通讯作者: Zhang Ming-Rong

Peking University/Nanjing Medical University/Beijing Institute of Technology(中国)

北京大学/南京医科大学/北京理工大学（中国）

In vivo PET imaging of cancer α5β1-integrin using a pegylated peptide

使用聚乙二醇化肽对癌症 α5β1-整合素进行体内 PET 成像

• 发表时间: 2021
• 作者: Hu Kuan ;謝 琳 ;張 一鼎 ;破入 正行 ;張 明栄:
• 通讯作者: 張 明栄:

Massachusetts General Hospital(米国)

马萨诸塞州总医院（美国）

PEGylation modulation of peptides promotes PET detection of cancers

肽的聚乙二醇化调节促进癌症的 PET 检测

• 发表时间: 2021
• 作者: Hu Kuan ;Xie Lin ;Yiding Zhang ;Hanyu Masayuki ;Zhang Ming-Rong
• 通讯作者: Zhang Ming-Rong