Wang Jingwen, Feng Lixia, Long Xingru, Yang Hao, Zhang Li, Hu Wenzhu, Chen Haibo, Jiang Dawei, Zhao Yongsheng, Hu Shu, Lan Xiaoli, Cao Wei
Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Hubei Key Laboratory of Molecular Imaging, Wuhan 430022, China.
Mol Pharm. 2025 Jul 7;22(7):4068-4075. doi: 10.1021/acs.molpharmaceut.5c00339. Epub 2025 Jun 22.
Neuroaxonal guidance factor-1 (Netrin-1) is a secreted glycoprotein overexpressed in cancer. It promotes tumor growth and metastasis and has demonstrated potential as a biomarker for tumor theranostics. In this study, we developed a novel Ga-68 labeled peptide radiotracer, termed [Ga]Ga-DKP, to assess the expression of netrin-1 in tumors. The tracer exhibited high radiochemical purity (over 95%) and strong stability. In vitro cellular assays demonstrated that A549 and 4T1 cells exhibited stronger binding capabilities for the probe than those in A375 cells, as they expressed higher levels of netrin-1. Furthermore, a blocking assay in A549 cells confirmed the affinity and specificity of the probe for netrin-1. In vivo PET/CT imaging and biodistribution studies demonstrated rapid tumor uptake and tissue excretion. A549 and 4T1 tumor-bearing mice showed higher tumor-to-muscle ratios (9.70 ± 1.24 and 10.94 ± 3.44, respectively) at 2 h postinjection, which were approximately 3-fold higher than A375 tumors. In conclusion, [Ga]Ga-DKP could be used to quantify netrin-1 levels, showing potential for clinical application.
神经轴突导向因子-1（Netrin-1）是一种在癌症中过表达的分泌型糖蛋白。它促进肿瘤生长和转移，并已显示出作为肿瘤诊疗生物标志物的潜力。在本研究中，我们开发了一种新型的镓-68标记肽放射性示踪剂，称为[Ga]Ga-DKP，以评估肿瘤中Netrin-1的表达。该示踪剂具有高放射化学纯度（超过95%）和强稳定性。体外细胞实验表明，A549和4T1细胞对该探针的结合能力比A375细胞更强，因为它们表达更高水平的Netrin-1。此外，A549细胞中的阻断实验证实了该探针对Netrin-1的亲和力和特异性。体内PET/CT成像和生物分布研究表明肿瘤摄取迅速且组织排泄快。注射后2小时，荷A549和4T1肿瘤的小鼠显示出更高的肿瘤与肌肉比值（分别为9.70±1.24和10.94±3.44），约为荷A375肿瘤小鼠的3倍。总之，[Ga]Ga-DKP可用于定量Netrin-1水平，显示出临床应用潜力。
