Zhang Xiaojun, Huang Yong, Gong Fengping, Chen Keyin, Zhang Yongqiang, Jie Zhisheng, Huang Jiawen, Tang Ganghua
Key Laboratory Project of Guangdong Provincial Department of Education for Ordinary Universities and GDMPA Key Laboratory for Quality Control and Evaluation of Radiopharmaceuticals, Department of Nuclear Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province 510515, China.
Department of Nuclear Medicine, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, China.
J Med Chem. 2025 Jul 10;68(13):14028-14040. doi: 10.1021/acs.jmedchem.5c01189. Epub 2025 Jun 28.
Integrin αvβ6 is an attractive target for theranostic applications in pancreatic ductal adenocarcinoma (PDAC). Yet, there remains a lack of an ideal PET/CT tracer targeting αvβ6. In this study, we designed two novel PET/CT tracers [F]AlF-Glc-αvβ6L and [F]AlF-Asp2-αvβ6L with hydrophilic linkers. Both [F]AlF-Glc-αvβ6L and [F]AlF-Asp2-αvβ6L demonstrated favorable and properties, which are characterized by high hydrophilicity. In pancreatic tumor-bearing mice, micro-PET/CT imaging and biodistribution studies demonstrated that both [F]AlF-Glc-αvβ6L and [F]AlF-Asp2-αvβ6L had favorable pharmacokinetic properties, good specific targeting to αvβ6, and tumor-to-background contrast. Between them, [F]AlF-Asp2-αvβ6L demonstrated superior stability and accelerated renal clearance than [F]AlF-Glc-αvβ6L, with comparable tumor uptake and retention and significantly lower kidney uptake. The results indicate that [F]AlF-Asp2-αvβ6L is a promising PET/CT tracer for PDAC imaging.
整合素αvβ6是胰腺导管腺癌（PDAC）诊疗应用中一个有吸引力的靶点。然而，目前仍缺乏一种理想的靶向αvβ6的PET/CT示踪剂。在本研究中，我们设计了两种带有亲水性连接体的新型PET/CT示踪剂[F]AlF-Glc-αvβ6L和[F]AlF-Asp2-αvβ6L。[F]AlF-Glc-αvβ6L和[F]AlF-Asp2-αvβ6L均表现出良好的性质，其特点是具有高亲水性。在荷胰腺肿瘤小鼠中，微型PET/CT成像和生物分布研究表明，[F]AlF-Glc-αvβ6L和[F]AlF-Asp2-αvβ6L均具有良好的药代动力学性质，对αvβ6具有良好的特异性靶向性，且肿瘤与背景对比度良好。其中，[F]AlF-Asp2-αvβ6L比[F]AlF-Glc-αvβ6L表现出更高的稳定性和更快的肾清除率，肿瘤摄取和滞留相当，肾脏摄取显著更低。结果表明，[F]AlF-Asp2-αvβ6L是一种有前景的用于PDAC成像的PET/CT示踪剂。
