Ren Jimin, Trokowski Robert, Zhang Shanrong, Malloy Craig R, Sherry A Dean
Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Magn Reson Med. 2008 Nov;60(5):1047-55. doi: 10.1002/mrm.21722.
Noninvasive imaging of glucose in tissues could provide important insights about glucose gradients in tissue, the origins of gluconeogenesis, or perhaps differences in tissue glucose utilization in vivo. Direct spectral detection of glucose in vivo by (1)H NMR is complicated by interfering signals from other metabolites and the much larger water signal. One potential way to overcome these problems is to use an exogenous glucose sensor that reports glucose concentrations indirectly through the water signal by chemical exchange saturation transfer (CEST). Such a method is demonstrated here in mouse liver perfused with a Eu(3+)-based glucose sensor containing two phenylboronate moieties as the recognition site. Activation of the sensor by applying a frequency-selective presaturation pulse at 42 ppm resulted in a 17% decrease in water signal in livers perfused with 10 mM sensor and 10 mM glucose compared with livers with the same amount of sensor but without glucose. It was shown that livers perfused with 5 mM sensor but no glucose can detect glucose exported from hepatocytes after hormonal stimulation of glycogenolysis. CEST images of livers perfused in the magnet responded to changes in glucose concentrations demonstrating that the method has potential for imaging the tissue distribution of glucose in vivo.
组织中葡萄糖的无创成像可以提供有关组织中葡萄糖梯度、糖异生的起源，或者体内组织葡萄糖利用差异等方面的重要见解。通过¹H NMR对体内葡萄糖进行直接光谱检测会受到来自其他代谢物的干扰信号以及大得多的水信号的影响。克服这些问题的一种潜在方法是使用一种外源性葡萄糖传感器，该传感器通过化学交换饱和转移（CEST）间接通过水信号报告葡萄糖浓度。本文在灌注了基于Eu(3+)的葡萄糖传感器的小鼠肝脏中展示了这种方法，该传感器含有两个苯基硼酸酯部分作为识别位点。通过在42 ppm处施加频率选择性预饱和脉冲激活传感器，与灌注相同量传感器但无葡萄糖的肝脏相比，在灌注10 mM传感器和10 mM葡萄糖的肝脏中，水信号降低了17%。结果表明，灌注5 mM传感器但无葡萄糖的肝脏在糖原分解激素刺激后能够检测到从肝细胞输出的葡萄糖。在磁体中灌注的肝脏的CEST图像对葡萄糖浓度变化有反应，表明该方法具有对体内葡萄糖组织分布进行成像的潜力。
