大肠癌ddr1靶向示踪剂的合成及临床前评价

IF 6.8 1区医学 Q1 CHEMISTRY, MEDICINAL

Journal of Medicinal Chemistry Pub Date : 2025-10-24 DOI:10.1021/acs.jmedchem.5c01224

Yuze Ma,Jingyue Gao,Kunyao Wang,Wenqi Zhao,Feng Gao

{"title":"大肠癌ddr1靶向示踪剂的合成及临床前评价","authors":"Yuze Ma,Jingyue Gao,Kunyao Wang,Wenqi Zhao,Feng Gao","doi":"10.1021/acs.jmedchem.5c01224","DOIUrl":null,"url":null,"abstract":"Colorectal cancer (CRC) is one of the most common tumors, and discoidin domain receptor 1 (DDR1) expression is significantly higher in CRC. In this study, we designed and synthesized eight novel 68Ga-labeled DDR1-targeted radiotracers. The radiochemical purities (RCPs) of radiotracers were all over 95%; except for [68Ga]Ga-MYZ02 and [68Ga]Ga-MYZ06, other six radiotracers showed high stability in vitro and in vivo. The equilibrium dissociation constants (KD) of radiotracers were all in the nanomolar range. Micro-PET/CT imaging and biodistribution study showed that [68Ga]Ga-MYZ04, which exhibits favorable pharmacokinetic properties, could clearly visualize tumors at 1 h postinjection. Among the six radiotracers, [68Ga]Ga-MYZ04 had the highest tumor-to-muscle ratio (T/M: 4.21 ± 0.51), a higher tumor-to-liver ratio (T/L: 0.71 ± 0.06), and the lowest tumor-to-kidney ratio (T/K: 0.55 ± 0.03), suggesting a superior metabolic pathway with primary clearance through the urinary system. This makes it promising for the imaging diagnosis of DDR1-positive expressing CRC.","PeriodicalId":46,"journal":{"name":"Journal of Medicinal Chemistry","volume":"108 1","pages":""},"PeriodicalIF":6.8000,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Synthesis and Preclinical Evaluation of DDR1-Targeted Radiotracers for Colorectal Cancer Diagnosis.\",\"authors\":\"Yuze Ma,Jingyue Gao,Kunyao Wang,Wenqi Zhao,Feng Gao\",\"doi\":\"10.1021/acs.jmedchem.5c01224\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Colorectal cancer (CRC) is one of the most common tumors, and discoidin domain receptor 1 (DDR1) expression is significantly higher in CRC. In this study, we designed and synthesized eight novel 68Ga-labeled DDR1-targeted radiotracers. The radiochemical purities (RCPs) of radiotracers were all over 95%; except for [68Ga]Ga-MYZ02 and [68Ga]Ga-MYZ06, other six radiotracers showed high stability in vitro and in vivo. The equilibrium dissociation constants (KD) of radiotracers were all in the nanomolar range. Micro-PET/CT imaging and biodistribution study showed that [68Ga]Ga-MYZ04, which exhibits favorable pharmacokinetic properties, could clearly visualize tumors at 1 h postinjection. Among the six radiotracers, [68Ga]Ga-MYZ04 had the highest tumor-to-muscle ratio (T/M: 4.21 ± 0.51), a higher tumor-to-liver ratio (T/L: 0.71 ± 0.06), and the lowest tumor-to-kidney ratio (T/K: 0.55 ± 0.03), suggesting a superior metabolic pathway with primary clearance through the urinary system. This makes it promising for the imaging diagnosis of DDR1-positive expressing CRC.\",\"PeriodicalId\":46,\"journal\":{\"name\":\"Journal of Medicinal Chemistry\",\"volume\":\"108 1\",\"pages\":\"\"},\"PeriodicalIF\":6.8000,\"publicationDate\":\"2025-10-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Medicinal Chemistry\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1021/acs.jmedchem.5c01224\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Medicinal Chemistry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1021/acs.jmedchem.5c01224","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}

引用次数: 0

摘要

结直肠癌（Colorectal cancer， CRC）是最常见的肿瘤之一，盘状蛋白结构域受体1 （disidin domain receptor 1, DDR1）在结直肠癌中的表达显著升高。在这项研究中，我们设计并合成了8种新型的68ga标记的ddr1靶向放射性示踪剂。放射性示踪剂放射化学纯度（rcp）均在95%以上；除[68Ga]Ga-MYZ02和[68Ga]Ga-MYZ06外，其余6种示踪剂均表现出较高的体内外稳定性。示踪剂的平衡解离常数（KD）均在纳摩尔范围内。微pet /CT成像及生物分布研究表明，[68Ga]Ga-MYZ04在注射后1 h能清晰地显示肿瘤，具有良好的药代动力学特性。在6种放射性示踪剂中，[68Ga]Ga-MYZ04具有最高的肿瘤-肌肉比（T/M: 4.21±0.51），较高的肿瘤-肝脏比（T/L: 0.71±0.06），最低的肿瘤-肾脏比（T/K: 0.55±0.03），提示其具有通过泌尿系统初步清除的优越代谢途径。这为ddr1阳性表达CRC的影像学诊断提供了前景。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

查看原文本刊更多论文

Synthesis and Preclinical Evaluation of DDR1-Targeted Radiotracers for Colorectal Cancer Diagnosis.

Colorectal cancer (CRC) is one of the most common tumors, and discoidin domain receptor 1 (DDR1) expression is significantly higher in CRC. In this study, we designed and synthesized eight novel 68Ga-labeled DDR1-targeted radiotracers. The radiochemical purities (RCPs) of radiotracers were all over 95%; except for [68Ga]Ga-MYZ02 and [68Ga]Ga-MYZ06, other six radiotracers showed high stability in vitro and in vivo. The equilibrium dissociation constants (KD) of radiotracers were all in the nanomolar range. Micro-PET/CT imaging and biodistribution study showed that [68Ga]Ga-MYZ04, which exhibits favorable pharmacokinetic properties, could clearly visualize tumors at 1 h postinjection. Among the six radiotracers, [68Ga]Ga-MYZ04 had the highest tumor-to-muscle ratio (T/M: 4.21 ± 0.51), a higher tumor-to-liver ratio (T/L: 0.71 ± 0.06), and the lowest tumor-to-kidney ratio (T/K: 0.55 ± 0.03), suggesting a superior metabolic pathway with primary clearance through the urinary system. This makes it promising for the imaging diagnosis of DDR1-positive expressing CRC.

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

来源期刊

Journal of Medicinal Chemistry 医学-医药化学

CiteScore

4.00

自引率

11.00%

发文量

804

审稿时长

1.9 months

期刊介绍： The Journal of Medicinal Chemistry is a prestigious biweekly peer-reviewed publication that focuses on the multifaceted field of medicinal chemistry. Since its inception in 1959 as the Journal of Medicinal and Pharmaceutical Chemistry, it has evolved to become a cornerstone in the dissemination of research findings related to the design, synthesis, and development of therapeutic agents. The Journal of Medicinal Chemistry is recognized for its significant impact in the scientific community, as evidenced by its 2022 impact factor of 7.3. This metric reflects the journal's influence and the importance of its content in shaping the future of drug discovery and development. The journal serves as a vital resource for chemists, pharmacologists, and other researchers interested in the molecular mechanisms of drug action and the optimization of therapeutic compounds.