Imaging iNOS and ROS/RNS

TR&D 3项目摘要 TR&D 3的主要目标是开发PET放射性药物， 炎症和氧化应激之间的联系值得注意的是， 氧化应激代表了 活性氧簇（ROS）的产生以及抗氧化剂对其的消除或缓解。过量的ROS 在多种疾病的发病机制中起着重要作用。重要的是，氧化应激的一个关键介质是一氧化氮 由一氧化氮合酶（NOS）家族酶产生的一氧化氮（NO）。在这个NOS家族中， 诱导型NO与多种疾病有关，其中急性或慢性疾病 炎症是疾病发病机制的中心。此外，过量的NO可以与自由基反应以产生 活性氮物质（RNS），如过氧亚硝酸盐，从而损害细胞功能。鉴于高 上述分子靶点在疾病发病机制中的重要性，TR&D 3的具体目标 设计、合成和验证：1）靶向诱导型一氧化氮合酶（iNOS）的放射性示踪剂; 2） 镓-68掺入PET示踪剂用于成像ROS/RNS介导的氧化应激。开发的放射性示踪剂 在TR&D 3中，将在我们机构的动物模型中进行初步验证。目标灵敏度确认后 和-特异性的新PET示踪剂在分子水平上在体内使用建议的方法，TR&D 3将 与CP合作验证并进一步优化技术，以广泛应用于特定疾病 应用.总的来说，这些PET示踪剂将提供新的成像资源，以询问这些重要的 炎症中的生物标志物。 涉及

TR&D 3 Project Summary The primary goal of TR&D 3 is to develop PET radiopharmaceuticals to enable molecular imaging of interplay between inflammation and oxidative stress. Of note, oxidative stress represents an imbalance between production of reactive oxygen species (ROS) and their elimination or mitigation by antioxidants. Excess ROS is in the pathogenesis of a wide range of diseases. Importantly, a key mediator of oxidative stress is nitric oxide (NO) which is generated by the nitric oxide synthase (NOS) family of enzymes. Among this NOS family, the inducible form of NO has been implicated in a variety of diseases, wherein either acute or chronic inflammation is central to disease pathogenesis. Moreover, excess NO can react with free radicals to generate reactive nitrogen species (RNS) such as peroxynitrites, thus impairing cell function. In view of the high significance of abovementioned molecular targets in the pathogenesis of disease, the specific aims of TR&D 3 are to design, synthesize, and validate: 1) radiotracers targeting inducible nitric oxide synthase (iNOS); and 2) gallium-68 incorporated PET tracers for imaging ROS/RNS-mediated oxidative stress. Radiotracers developed in TR&D 3 will be initially validated in animal models at our institution. Following validations of target-sensitivity and –specificity of new PET tracers at a molecular level in vivo using proposed methodologies, TR&D 3 will collaborate with CPs to validate and further optimize the technology for wide utility in disease-specific applications. Overall, these PET tracers will provide novel imaging resource to interrogate role of these vital biomarkers in inflammation. involved