Key Laboratory of Radiopharmaceuticals of the Ministry of Education, NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Products Administration), College of Chemistry, Beijing Normal University, Beijing 100875, P. R. China.
Key Laboratory of Beam Technology of the Ministry of Education, College of Nuclear Science and Technology, Beijing Normal University, Beijing 100875, P. R. China.
J Med Chem. 2023 Apr 13;66(7):4952-4960. doi: 10.1021/acs.jmedchem.2c02062. Epub 2023 Mar 27.
Fibroblast activation protein (FAP) is a potential target for tumor diagnosis and treatment due to its selective expression on cancer-associated fibroblasts (CAFs) in most solid tumor stroma. Two FAP inhibitor (FAPI) derived ligands (L1 and L2) containing different lengths of Pro-Gly (PG) repeat units as linkers were designed and synthesized with high affinity for FAP. Two stable hydrophilic Tc-labeled complexes ([Tc]Tc-L1 and [Tc]Tc-L2) were obtained. cellular studies show that the uptake mechanism is correlated with FAP uptake, and [Tc]Tc-L1 shows a higher cell uptake and specific binding to FAP. A nanomolar value for [Tc]Tc-L1 indicates its significantly high target affinity for FAP. The biodistribution and microSPECT/CT images obtained for U87MG tumor mice show that [Tc]Tc-L1 has high tumor uptake with specificity to FAP and high tumor-to-nontarget ratios. As an inexpensive, easily made, and widely available tracer, [Tc]Tc-L1 holds great promise for clinical applications.
成纤维细胞激活蛋白（FAP）在大多数实体肿瘤基质中的癌相关成纤维细胞（CAFs）上选择性表达，因此成为肿瘤诊断和治疗的潜在靶点。设计并合成了两种含有不同长度脯氨酸-甘氨酸（PG）重复单元作为连接物的 FAP 抑制剂（FAPI）衍生配体（L1 和 L2），它们对 FAP 具有高亲和力。获得了两种稳定的亲水性 Tc 标记的配合物（[Tc]Tc-L1 和 [Tc]Tc-L2）。细胞研究表明，摄取机制与 FAP 摄取相关，[Tc]Tc-L1 表现出更高的细胞摄取和对 FAP 的特异性结合。[Tc]Tc-L1 的纳摩尔值表明其对 FAP 的靶标亲和力显著较高。U87MG 肿瘤小鼠的生物分布和 microSPECT/CT 图像显示，[Tc]Tc-L1 具有高肿瘤摄取特异性和高肿瘤与非靶标比值。作为一种廉价、易于制备且广泛可用的示踪剂，[Tc]Tc-L1 在临床应用中具有很大的应用前景。
