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

为了提高体内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。而l波段ESR测量强度仅增加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分布和代谢。结果发现，ACP分布于脑内，但与肝脏相比，脑内的水解速度相对较慢，在肝脏中，大部分注射的ACP在10分钟内转化为羟胺。我们在使用ACP时应谨慎选择最佳时间，以获得良好的体内ESR测量结果。合成了几种PROXYL衍生物。用体内ESR法测定这些探针在小鼠头部区域的分布和滞留。羟甲基和乙酰氧基甲氧羰基衍生物的ESR信号衰减缓慢，而甲氧羰基衍生物的ESR信号衰减呈双相，表明这两种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.