Radiofluorinated Smart Probes for Noninvasive PET Imaging of Legumain Activity in Living Subjects
| Autor: | Ling Qiu, Yann Seimbille, Jianguo Lin, Gaochao Lv, Ke Li, Ying Peng, Qingzhu Liu, Minhao Xie, Xi Li |
|---|---|
| Přispěvatelé: | Radiology & Nuclear Medicine |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
Treatment response Fluorine Radioisotopes Cell Membrane Permeability Legumain activity Contrast Media Glutamic Acid Mice Nude Biosensing Techniques 010402 general chemistry Legumain 01 natural sciences Sensitivity and Specificity Analytical Chemistry Metastasis Mice medicine Animals Humans Histidine medicine.diagnostic_test biology Molecular Structure business.industry Chemistry 010401 analytical chemistry Single injection Pet imaging Neoplasms Experimental medicine.disease HCT116 Cells 0104 chemical sciences Cysteine Endopeptidases Positron emission tomography Isotope Labeling Positron-Emission Tomography biology.protein Female Imaging technique Radiopharmaceuticals Nuclear medicine business Peptides |
| Zdroj: | Analytical Chemistry, 92(17), 11627-11634. American Chemical Society |
| ISSN: | 1520-6882 0003-2700 |
| Popis: | 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 (18F-2 and 18F-3) as well as a control probe (18F-1) were specifically designed for PET imaging of legumain activity in tumors. 18F-1, 18F-2, and 18F-3 were obtained with high radiochemical yield (RCY > 60%) and radiochemical purity (RCP > 99%) using a convenient "one-step" 18F-labeling method. The probes 18F-2 and 18F-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 18F-2 and 18F-3, respectively; 8.46% ± 0.33% and 9.05% ± 0.24% for co-treatment of 18F-2 + 2 and 18F-3 + 3 at 1 h), while the control probe 18F-1 showed no response. PET imaging of tumor-bearing mice showed that the co-injection strategy (18F-2 + 2 and 18F-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 18F-2 and 18F-3, respectively). In addition, introduction of the trimeric histidine-glutamate (HEHEHE) tag to 18F-3 reduced the liver uptake by almost two-fold without any noticeable effect on the tumor uptake. All the results indicate that 18F-3 holds great potential applications in clinics for sensitive and specific PET imaging of legumain activity in tumors. |
| Databáze: | OpenAIRE |
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