Stabilized peptide targeting programmed death-ligand 1 for Positron Emission Tomography imaging and cancer immunotherapy

用于正电子发射断层扫描成像和癌症免疫治疗的靶向程序性死亡配体 1 的稳定肽

• 批准号: 18H06217
• 负责人: 胡 寛
• 金额: $ 1.91万
• 依托单位: National Institutes for Quantum and Radiological Science and Technology
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Research Activity Start-up
• 财政年份: 2018
• 资助国家: 日本
• 起止时间: 2018-08-24 至 2020-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-18H06217/
• 关键词: stabilized peptide; PD-L1; PET imaging

I developed a native peptide-based PET tracer for imaging tumor PD-L1 for the first time. I labeled the peptide with 18F and 64Cu. Moreover, the peptide was pegylated to form PEG-peptide conjugates via an optimum ‘one-pot’ strategy. The as-made radiotracers were evaluated for stability and specificity in vitro and imaged in normal mice and in a tumor model. As consequence, the 64Cu labeled compounds showed preferable imaging potential in vivo. Furthermore, the pegylation was demonstrated to change the pharmacokinetics and biodistribution of the tracers. Our studies suggested that native peptide-based tracers are capable of PD-L1 imaging, further improvement of the performance via rational design and exactly under current investigation.These results were published in Chem Commun.

我首次开发了一种基于天然肽的 PET 示踪剂，用于对肿瘤 PD-L1 进行成像，并使用 18F 和 64Cu 标记该肽，并且通过最佳“一锅法”策略将该肽聚乙二醇化以形成 PEG-肽缀合物。在体外评估了所制成的放射性示踪剂的稳定性和特异性，并在正常小鼠和肿瘤模型中进行成像，结果表明 64Cu 标记的化合物在体内表现出更好的成像潜力。此外，聚乙二醇化被证明可以改变示踪剂的药代动力学和生物分布。我们的研究表明，基于天然肽的示踪剂能够进行 PD-L1 成像，通过合理的设计和当前的研究进一步提高了性能。这些结果是。发表于《化学通讯》。

项目成果

Develop a peptide-based PET radiotracer for imaging PD-L1 expression in cancer

开发基于肽的 PET 放射性示踪剂，用于对癌症中的 PD-L1 表达进行成像

• 发表时间: 2019
• 作者: Kuan Hu;Lin Xie;Masayuki Hanyu;Yiding Zhang;Ming-Rong Zhang
• 通讯作者: Ming-Rong Zhang

Radiolabeled Peptide for Anti-PD-L1 Imaging and Therapy

用于抗 PD-L1 成像和治疗的放射性标记肽

• 发表时间: 2018
• 作者: Hu Kuan ;謝 琳 ;破入 正行 ;張 明栄
• 通讯作者: 張 明栄