NHC Key Laboratory of Nuclear Medicine, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, China.
Department of Radiopharmaceuticals, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China.
Anal Chem. 2020 Sep 1;92(17):11627-11634. doi: 10.1021/acs.analchem.0c01253. Epub 2020 Aug 12.
Overexpression of legumain is closely associated with tumor proliferation, invasion, and metastasis. Because of its intrinsic properties, such as high sensitivity and resolution, positron emission tomography (PET) has become an effective imaging technique for early diagnosis, treatment response prediction, and monitoring. Herein, two legumain-targeting radiofluorinated smart probes ( and ) as well as a control probe () were specifically designed for PET imaging of legumain activity in tumors. , , and were obtained with high radiochemical yield (RCY > 60%) and radiochemical purity (RCP > 99%) using a convenient "one-step" F-labeling method. The probes and exhibited high response to legumain activity and reductive environment and revealed comparable uptake in HCT116 cells (4.22% ± 0.14% and 4.64% ± 0.32% for and , respectively; 8.46% ± 0.33% and 9.05% ± 0.24% for co-treatment of and at 1 h), while the control probe showed no response. PET imaging of tumor-bearing mice showed that the co-injection strategy ( and ) resulted in higher tumor uptake (3.57% ± 0.37% and 3.72% ± 0.19% ID/g at 10 min, respectively) than the single injection strategy (2.59% ± 0.19% and 2.60% ± 0.46% ID/g for and , respectively). In addition, introduction of the trimeric histidine-glutamate (HEHEHE) tag to reduced the liver uptake by almost two-fold without any noticeable effect on the tumor uptake. All the results indicate that holds great potential applications in clinics for sensitive and specific PET imaging of legumain activity in tumors.
组织蛋白酶 L 的过表达与肿瘤的增殖、侵袭和转移密切相关。由于其固有特性，如高灵敏度和分辨率，正电子发射断层扫描（PET）已成为肿瘤早期诊断、治疗反应预测和监测的有效成像技术。在此，我们专门设计了两种组织蛋白酶 L 靶向放射性氟代智能探针（和）以及一种对照探针（），用于 PET 成像组织蛋白酶 L 活性。使用方便的“一步”F-标记法，以高放射化学产率（RCY>60%）和放射化学纯度（RCP>99%）获得、、。探针和对组织蛋白酶 L 活性和还原环境具有高响应性，并在 HCT116 细胞中显示出相当的摄取（和分别为 4.22%±0.14%和 4.64%±0.32%；和共处理 1 h 时分别为 8.46%±0.33%和 9.05%±0.24%），而对照探针则没有响应。荷瘤小鼠的 PET 成像显示，与单注射策略相比，联合注射策略（和）导致肿瘤摄取更高（分别为 10 min 时的 3.57%±0.37%和 3.72%±0.19% ID/g）。此外，将三聚组氨酸-谷氨酸（HEHEHE）标签引入到中，可使肝脏摄取减少近两倍，而对肿瘤摄取几乎没有任何明显影响。所有结果表明，在临床上具有很大的潜力，可用于肿瘤组织蛋白酶 L 活性的敏感和特异性 PET 成像。
