Establishnent of In vivo ESR Imaging System for Oxidativte Stress in Brain

为了提高在体ESR成像测量的灵敏度和分辨率，合成了含有[^2H]的自旋探针。在X波段ESR测量中，探针的信号强度增加了约1.5倍。然而，L波段ESR测量的强度仅增加了1.14倍。另一种制备[^<15>N]自旋探针的方法正在进行中，合成了一种羟胺型探针ACP，并测定了其在小鼠体内的全身分布和代谢。结果表明，ACP主要分布在脑内，但在脑内的水解速度比在肝内的慢，肝内注射的ACP在10 min内就可全部转化为羟胺。用活体ESR法测定了探针在小鼠头部的分布和滞留。ESR信号的缓慢衰减观察到的羟甲基和乙酰氧基甲氧基羰基衍生物，而双相衰减观察到的甲氧基羰基衍生物，表明这些探针在大脑中的分布和代谢是不同的。

To increase the sensitivity and resolution in the measurement of in vivo ESR imaging, spin probes containing [^2H] were synthesized. The signal intensity of the probes increased about 1.5 times in X-band ESR measurement. However, the increase of the intensity in L-band ESR measurement was only 1.14 times. Another approach preparing [^<15>N] spin probes is in progress.A hydroxylamine type probe, ACP, was synthesized and its whole body distribution and metabolism in mice were measured. It was found that ACP is distributed in the brain but the hydrolysis in the brain is relatively slow compared to that in the liver where most of the injected ACP is converted to hydroxylamine in 10 min. We should be careful in using ACP for choosing the best timing to get good results by in vivo ESR measurement.Several PROXYL derivatives were synthesized. The distribution and retention of these probes in mouse head region were measured by in vivo ESR. Slow decay of the ESR signal was observed for the hydroxymethyl- and acetoxymethoxycarbonyl-derivatives, whereas biphasic decay was observed for the methoxycarbonyl-derivative, indicating that the distribution and metabolism of these probes in the brain are different.