Native Ligand-Inspired peptides for c-MET targeted PET probes development
文献类型：期刊论文
| 作者 | Luo, Renli5,7; Tan, Boyu3,5; Zhang, Ying5; Hu, Jing5,6; Lin, Jia5,6; Sun, Luming5; Wei, Xiaonan5; Ju, Nianting4,5; Luo, Xiangning5; Chen, Chuan5 |
| 刊名 | EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
 |
| 出版日期 | 2025-06-16 |
| 页码 | 18 |
| 关键词 | C-MET Native ligand HGF PET/CT imaging Radiopharmaceuticals Peptide probes |
| ISSN号 | 1619-7070 |
| DOI | 10.1007/s00259-025-07403-y |
| 英文摘要 | PurposeNative ligand-derived peptides have significantly advanced the development of targeting ligands in radiopharmaceutical discovery and design. Herein, we report the first attempt to develop novel mesenchymal-epithelial transition factor (c-MET) targeted peptide positron emission tomography (PET) probes based on the endogenous biomolecule, hepatocyte growth factor (HGF).MethodsThree c-MET targeted peptides were designed from the N-terminal and kringle 1 domain (NK1: 32-207 amino acid residues) of HGF. Then they were conjugated with chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and radiolabeled with [68Ga]GaCl3. The resulted [68Ga]Ga-labelled probes, [68Ga]Ga-DOTA-K1, [68Ga]Ga-DOTA-A-C5, and [68Ga]Ga-DOTA-A-M8 were evaluated in vitro and in vivo.ResultsAmong three PET probes, [68Ga]Ga-DOTA-A-M8 exhibited a high affinity for c-MET (IC50 = 5.43 nM) and demonstrated specific and high uptake in c-MET highly expressing HCT-116 cells. Small animal PET/CT imaging clearly visualized the tumor with good contrast using [68Ga]Ga-DOTA-A-M8 over 120 min. Quantitative analysis of PET images revealed tumor uptake of [68Ga]Ga-DOTA-A-M8 at 30 min post-injection was 2.91 +/- 0.20%ID/g in HCT-116 models. The probe was mainly cleared out through the kidney-bladder pathway. Biodistribution study showed HCT-116 tumor uptake of 2.84 +/- 0.07%ID/g and 0.54 +/- 0.09%ID/g in the normal and blocking mice group, respectively, at 30 min post-injection. The tumor-to-muscle, tumor-to-blood and tumor-to-liver ratios were 3.60 +/- 1.09, 1.48 +/- 0.24 and 2.48 +/- 0.28, respectively, at 30 min.ConclusionA novel c-MET-targeting PET probe, [68Ga]Ga-DOTA-A-M8, has been successfully developed in this study. It demonstrates high tumor-targeting capability and specificity. This study highlights developing PET probes based on native ligands is a powerful and generalizable strategy. |
| 资助项目 | National Natural Science Foundation of China |
| WOS研究方向 | Radiology, Nuclear Medicine & Medical Imaging |
| 语种 | 英语 |
| WOS记录号 | WOS:001509370500001 |
| 出版者 | SPRINGER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/318401]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Luo, Quanyong; Cao, Rui; Cheng, Zhen |
| 作者单位 | 1.Bohai Rim Adv Res Inst Drug Discovery, Shandong Lab Yantai Drug Discovery, Yantai 264117, Shandong, Peoples R China 2.Univ Chinese Acad Sci, Sch Phys Sci, 19A YuQuan Rd, Beijing 100049, Peoples R China 3.ShanghaiTech Univ, Sch Biomed Engn, Shanghai 201210, Peoples R China 4.Shanghai Jiao Tong Univ, Sch Med, Shanghai Peoples Hosp 6, Dept Nucl Med, Shanghai, Peoples R China 5.Chinese Acad Sci, Shanghai Inst Mat Med, Mol Imaging Ctr, State Key Lab Drug Res, Shanghai 201203, Peoples R China 6.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China 7.Northeastern Univ, Inst Mol Med, Coll Life & Hlth Sci, Shenyang 110167, Peoples R China |
| 推荐引用方式 GB/T 7714 | Luo, Renli,Tan, Boyu,Zhang, Ying,et al. Native Ligand-Inspired peptides for c-MET targeted PET probes development[J]. EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING,2025:18. |
| APA | Luo, Renli.,Tan, Boyu.,Zhang, Ying.,Hu, Jing.,Lin, Jia.,...&Cheng, Zhen.(2025).Native Ligand-Inspired peptides for c-MET targeted PET probes development.EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING,18. |
| MLA | Luo, Renli,et al."Native Ligand-Inspired peptides for c-MET targeted PET probes development".EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING (2025):18. |
入库方式： OAI收割
来源：上海药物研究所
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