JOINT RESEARCH ON IN VIVO ESR IMAGING AND SPECTROSCOPY

电子自旋共振波谱是一种检测和识别体内自由基并追踪其生理功能的独特方法。然而，这种方法已经不能满足包括医学和生理学在内的生物科学的迫切要求。到目前为止，我们已经研究了一些小动物的ESR成像方法，并成功地构建了拍摄小动物体内自由基分布的低频设备。在本项目中，我们旨在考察适合于达特茅斯医学小组开发的设备的自旋探针试剂，并试图探索一种开发体内ESR成像和ESR波谱来诊断人类疾病的方法学。实际上，每组开发的样品都被相互交换并引入合适的研究系统。典型结果如下：(1)成功地合成了检测生物细胞中产生的活性氧(ROS)的新型自旋探针；(2)建立了将该探针引入小动物体内并描绘体内产生的ROS分布的方法；(3)提供了一种检测体内氧浓度及其时间依赖性的标准自旋探针，用于比较两种ESR设备的灵敏度，两种设备的灵敏度没有根本差异，和(4)两个实验室建立的大鼠生物体的搜索线圈式ESR方法被证明是一种有效的体内诊断方法，可以估计拖拽和食物补充剂的影响。这些结果对我们研究所发展先进的ESR成像和光谱学是必不可少的，并有望广泛应用于活体生物系统。

ESR spectroscopy has been a unique method detecting and identifying in vivo free radicals, and tracing their physiological functions. However, this method has not been responding urgent requirements from biological sciences including medicine and physiology. We have so far investigated some ESR imaging methods for small animals and succeeded to construct low-frequency equipments picturing in vivo distributions of the free radicals in small animals.In this project we aimed to survey the spin-probe reagents suitable for the equipments which were developed by the Dartmouth medical group, and in addition we tried to investigate a methodology developing in vivo ESR imaging and ESR spectroscopy for diagnosis of human diseases. Actually the samples developed in each group were exchanged each other and introduced to suitable research systems. Typical results are as follows : (1) Novel spin probes detecting reactive oxygen species(ROS) generated in biological cells were succeeded to synthesize, (2) Methods introducing the probes to the body of small animals and picturing the distribution of ROS generated in vivo were established, (3) A standard spin probe detecting in vivo oxygen concentration and its time dependence was supplied for the estimation of both sensitivities of ESR equipments used to compare each other, and there was no fundamental difference of the sensitivities between both equipments, and (4) A search-coil type ESR method developed in both laboratories for rat organisms were shown to be an efficient in vivo diagnosis method estimating the effects of drags and food supplements. These results are essential to develop advanced ESR imaging and spectroscopy in our institute and expected to be widely applied for in vivo biological systems.