Lu Chunmei, Wang Xiuting, Wang Qiqi, Zhang Lixia, Lin Jianguo, Qiu Ling
School of Chemical and Material Engineering, Jiangnan University, Wuxi 214122, China.
NHC Key Laboratory of Nuclear Medicine, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, China.
Pharmaceuticals (Basel). 2022 Apr 27;15(5):543. doi: 10.3390/ph15050543.
Legumain has been found overexpressed in several cancers, which serves as an important biomarker for cancer diagnosis. In this research, a novel fluorine-18 labeled radioactive tracer [18F]SF-AAN targeting legumain was designed and synthesized for positron emission tomography (PET) imaging. Nonradioactive probe [19F]SF-AAN was obtained through chemical and solid phase peptide synthesis. After a simple one-step 18F labeling, the radiotracer [18F]SF-AAN was obtained with a high radiochemical conversion rate (>85%) and radiochemical purity (99%) as well as high molar activity (12.77 ± 0.50 MBq/nmol). The targeting specificity of [18F]SF-AAN for detecting legumain activity was investigated systematically in vitro and in vivo. In vitro cellular uptake assay showed that the uptake of [18F]SF-AAN in legumain-positive MDA-MB-468 cells was twice as much as that in legumain-negative PC-3 cells at 4 h. In vivo PET imaging revealed that the tumor uptake of [18F]SF-AAN in MDA-MB-468 tumor-bearing mice was about 2.7 times of that in PC-3 tumor-bearing mice at 10 min post injection. The experimental results indicated that [18F]SF-AAN could serve as a promising PET tracer for detecting the legumain expression sensitively and specifically, which would be beneficial for the diagnosis of legumain-related diseases.
天冬酰胺酶在多种癌症中被发现过表达，可作为癌症诊断的重要生物标志物。在本研究中，设计并合成了一种新型的靶向天冬酰胺酶的氟-18标记放射性示踪剂[18F]SF-AAN，用于正电子发射断层扫描（PET）成像。通过化学和固相肽合成获得非放射性探针[19F]SF-AAN。经过简单的一步18F标记，获得了放射性示踪剂[18F]SF-AAN，其具有高放射化学转化率（>85%）、放射化学纯度（99%）以及高摩尔活度（12.77±0.50 MBq/nmol）。系统地研究了[18F]SF-AAN检测天冬酰胺酶活性的靶向特异性，包括体外和体内实验。体外细胞摄取实验表明，在4小时时，[18F]SF-AAN在天冬酰胺酶阳性的MDA-MB-468细胞中的摄取量是天冬酰胺酶阴性的PC-3细胞中的两倍。体内PET成像显示，在注射后10分钟，[18F]SF-AAN在携带MDA-MB-468肿瘤的小鼠中的肿瘤摄取量约为携带PC-3肿瘤的小鼠中的2.7倍。实验结果表明，[18F]SF-AAN可作为一种有前景的PET示踪剂，用于灵敏且特异性地检测天冬酰胺酶的表达，这将有利于天冬酰胺酶相关疾病的诊断。
