Analysis of brain/heart pathogenesis based on mitochondiral function and its application to nuclear medicine.

线粒体是一种重要的胞内有氧能量生物，具有自己的基因和表达系统。正常情况下，线粒体和其他细胞内起源是紧密相连的，但这种联系的失败被认为是氧化应激的原因，如缺血再灌注损伤，特别是在大脑或心脏。了解这种联系的失败过程将为脑/心脏缺血性疾病的发病机制带来新的视角，并使我们能够发展新的核医学诊断方法。在这项研究中，已经开发了新的放射性铜标记的放射性药物，并且可以在疾病动物模型和人类患者中观察到电子传递失败。放射性碘化脂肪酸衍生物已被评价为心肌能量衰竭的标志物，其有用性有待阐明。对脑缺血/缺氧脑片摄取氟-18-氟代脱氧葡萄糖(FDG)的动态分析表明，自由基的形成和谷氨酸的释放对脑损伤可逆性的贡献是不同的。这种方法使我们能够在严格控制的条件下阐明药物对神经元损伤的影响。作为另一项研究，肿瘤的耐缺氧也可以与非肿瘤组织的缺氧进行比较。根据本工作的结果，可以成功地进行低氧肿瘤治疗性放射性药物的选择性放射治疗。

Mitochondiria is an important intracellular organism for aerobic energy production, having its own gene and expression system. Normally, mitochondria and other intracellular origanisms are closely linkaged, but failture in this linkage is said to be a cause of oxidative stress such as ischemia-reperfison injury, especially in brain or heart. Understanding the process of failure in this linkage will bring a new sight of pathogenesis of ishcemic disease in brain/heart and allow us to develop new diagnostic method in nuclear medicine. In this research, new radioactive copper labeled radiopharmacetucals, have been developmed and electron transport failure could be visualized in diseased animal models as well as human patients. Radioiodinated Fatty acid derivative has been evaluated as a marker of myocardial energy failure, and its usefulness could be clarified. Dynamic analysis of brain uptake of fluorine-18-labeled fluorodeoxyglucose (FDG) in ischemic/hypoxic brain slices brought us an difference in contribution of radical formation and glutamate release to the reversibility of damage in the brain. This methodology allows us to clarify the drug effect on neuronal damage under strictly controlled conditions.As an additional research, hypoxia tolerance of tumors can be also studied in comparison with hypoxia of non-tumor tissues. Based on the results of this work, development of therapeutic radiopharmaceutical for hypoxic tumor selective radiotherapy could be performed successfully.