Radiofluorinated Smart Probes for Noninvasive PET Imaging of Legumain Activity in Living Subjects
Radiofluorinated Smart Probes for Noninvasive PET Imaging of Legumain Activity in Living Subjects
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DOI：
10.1021/acs.analchem.0c01253
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发表时间：
2020-09-01
影响因子：
7.4
通讯作者：
Lin, Jianguo
中科院分区：
文献类型：
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作者：
Qiu, Ling;Li, Xi;Lin, Jianguo
豆科蛋白的过表达与肿瘤的增殖、侵袭和转移密切相关。正电子发射断层扫描（PET）由于其高灵敏度和高分辨率等固有特性，已成为早期诊断、治疗反应预测和监测的有效成像技术。本文设计了两种靶向豆类的放射性氟化智能探针（F-18-2和F-18-3）以及一种对照探针（F-18-1），专门用于肿瘤中豆类活性的PET成像。F-18-1、F-18-2和F-18-3具有较高的放射化学产率（RCY > 60%）和放射化学纯度（RCP > 99%），采用方便的“一步法”标记f -18。在HCT116细胞中，F-18-2和F-18-3对豆素活性和还原环境均有较高的反应，摄取率为4.22% +/- 0.14%和4.64% +/- 0.32%；F-18-2 + 2和F-18-3 + 3共处理1 h时分别为8.46% +/- 0.33%和9.05% +/- 0.24%，而对照探针F-18-1无反应。荷瘤小鼠PET显像显示，联合注射策略（F-18-2 + 2和F-18-3 + 3）比单独注射策略（F-18-2和18- F-3分别为2.59% +/- 0.19%和2.60% +/- 0.46% ID/g）的肿瘤摄取率更高（10 min时分别为3.57% +/- 0.37%和3.72% +/- 0.19%）。此外，将三聚组氨酸-谷氨酸（HEHEHE）标签引入F-18-3后，肝脏摄取减少了近两倍，而对肿瘤摄取没有明显影响。这些结果表明，F-18-3在临床上具有很大的应用潜力，可用于肿瘤中豆类活性的敏感和特异性PET成像。
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 (F-18-2 and F-18-3) as well as a control probe (F-18-1) were specifically designed for PET imaging of legumain activity in tumors.F-18-1, F-18-2, and F-18-3 were obtained with high radiochemical yield (RCY > 60%) and radiochemical purity (RCP > 99%) using a convenient "one-step" F-18-labeling method. The probes F-18-2 and F-18-3 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 F-18-2 and F-18-3, respectively; 8.46% +/- 0.33% and 9.05% +/- 0.24% for co-treatment of F-18-2 + 2 and F-18-3 + 3 at 1 h), while the control probe F-18-1 showed no response. PET imaging of tumor-bearing mice showed that the co-injection strategy (F-18-2 + 2 and F-18-3 + 3) 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 F-18-2 and 18 F-3, respectively). In addition, introduction of the trimeric histidine-glutamate (HEHEHE) tag to F-18-3 reduced the liver uptake by almost two-fold without any noticeable effect on the tumor uptake. All the results indicate that F-18-3 holds great potential applications in clinics for sensitive and specific PET imaging of legumain activity in tumors.