Department of Environmental and Life Sciences, University of Eastern Piedmont "A. Avogadro", Viale T. Michel 11, I-15121 Alessandria, Italy.
J Med Chem. 2010 Jul 8;53(13):4877-90. doi: 10.1021/jm901876r.
Four novel MRI Gd(III)-based probes have been synthesized and evaluated for their labeling properties on cultured cell lines K562, C6, and B16. The labeling strategy relies upon the fact that cells display a large number of reactive exofacial protein thiols (EPTs) that can be exploited as anchorage points for suitably activated MRI probes. The probes are composed of a Gd(III) chelate (based on either DO3A or DTPA) connected through a flexible linker to the 2-pyridyldithio chemical function for binding to EPTs. GdDO3A-based chelates could efficiently label cells (up to a level of 1.2 x 10(10) Gd(III) atoms/cell), whereas GdDTPA-based chelates showed poor or no cell labeling ability at all. Among the GdDO3A based compounds, that having the longest spacer (compound GdL1A) showed the best labeling efficacy. The mechanism of EPT mediated cell labeling by GdL1A involves probe internalization without sequestration of the Gd(III) chelate within subcellular structures such as endosomes.
已经合成了四种新型基于 MRI 的 Gd(III)探针，并对其在 K562、C6 和 B16 细胞系上的标记性能进行了评估。该标记策略依赖于这样一个事实，即细胞表面显示出大量的反应性细胞外蛋白硫醇 (EPTs)，这些硫醇可以作为适当激活的 MRI 探针的锚定点。探针由 Gd(III)螯合物（基于 DO3A 或 DTPA）通过柔性连接子与 2-吡啶基二硫化学功能连接，用于与 EPTs 结合。GdDO3A 基螯合物能够有效地标记细胞（高达 1.2 x 10(10) Gd(III) 原子/细胞），而 GdDTPA 基螯合物则根本没有或几乎没有细胞标记能力。在 GdDO3A 基化合物中，具有最长间隔基的化合物（GdL1A）显示出最佳的标记效果。GdL1A 通过 EPT 介导的细胞标记的机制涉及探针的内化，而 Gd(III)螯合物不会在内体等亚细胞结构中被隔离。
