Bio-orthogonal Metabolic Fluorine Labeling Enables Deep-Tissue Visualization of Tumor Cells In Vivo by 19F Magnetic Resonance Imaging.
Bio-orthogonal Metabolic Fluorine Labeling Enables Deep-Tissue Visualization of Tumor Cells In Vivo by 19F Magnetic Resonance Imaging.
复制标题
DOI：
10.1021/acs.analchem.2c02443
复制
发表时间：
2022-11
影响因子：
7.4
通讯作者：
Dongxia Chen;Yaying Lin;Ao Li;Xiangjie Luo;C. Yang;Jinhao Gao;Hongyu Lin
中科院分区：
文献类型：
--
作者：
Dongxia Chen;Yaying Lin;Ao Li;Xiangjie Luo;C. Yang;Jinhao Gao;Hongyu Lin
~(19)F磁共振成像具有分辨率高、穿透性强、生物背景可忽略不计等特点，为体内各种生物靶点的成像提供了潜在的手段。然而，目前的~(19)F-MRI探头的靶向策略有限，大大限制了它们在体内示踪低丰度靶和特定生物过程的应用，这极大地刺激了对新的~(19)F-MRI靶向方法的研究。在此，我们报告了一种被称为生物正交代谢氟标记的策略，用于选择性细胞19F标记，该策略允许在体内成像具有高特异性的肿瘤细胞。这一策略通过癌细胞对四乙酰化N-叠氮乙酰甘露糖胺(Ac4ManAz)的选择性摄取和代谢工程，以及随后叠氮基和环炔基团之间的快速和特异的生物正交连接，利用叠氮基在细胞表面的展示，将含19F的部分结合到癌细胞表面。我们用A549和HepG2细胞在细胞水平上验证了该方法的可行性，并进一步说明了该方法在A549荷瘤BALB/c小鼠体内应用HotSpot 19F MRI对癌细胞进行深层组织可视化的应用。我们的策略扩大了靶向19F磁共振成像的范围，并为组织渗透率高、生物背景低的活体对象提供了一种有前景的生物靶点成像方法。
The high resolution, deep penetration, and negligible biological background of 19F magnetic resonance imaging (MRI) makes it a potential means for imaging various biological targets in vivo. However, the limited targeting strategies of current 19F MRI probes significantly restrict their applications for in vivo tracking of low-abundance targets and specific biological processes, which greatly stimulates the investigations on new targeting methods for 19F MRI. Herein, we report a strategy, termed as bio-orthogonal metabolic fluorine labeling, for selective cellular 19F labeling, which permits in vivo imaging of tumor cells with high specificity. This strategy exploits the display of azido groups on the cell surface via selective uptake and metabolic engineering of tetra-acetylated N-azidoacetylmannosamine (Ac4ManAz) by cancer cells and subsequent rapid and specific bio-orthogonal ligation between azido and cyclootynyl groups to incorporate 19F-containing moieties on the surface of cancer cells. We validated the feasibility of this method on the cellular level with A549 and HepG2 cells and further illustrated the application of this method for in vivo deep-tissue visualization of cancer cells with A549 tumor-bearing BALB/c mice using hot spot 19F MRI. Our strategy expands the arsenal for targeted 19F MRI and provides a promising method for imaging biological targets in living subjects with high tissue penetration and low biological background.