Imaging iNOS and ROS/RNS

R&D 3项目总结 研发3的主要目标是开发PET放射性药物，使相互作用的分子成像成为可能 在炎症和氧化应激之间。值得注意的是， 氧化应激表现为 活性氧(ROS)的产生及其抗氧化剂的消除或缓解。过量的ROS是 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体是一氧化氮 一氧化氮(NO)是由一氧化氮合酶(NOS)家族产生的。在这个NOS家族中， NO的诱导性形式与多种疾病有关，其中急性或慢性疾病 炎症是疾病发病机制的核心。此外，过量的NO可以与自由基反应生成 活性氮(RN)，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意义、RT&D 3的具体目标 是设计、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) 掺入镓-68的PET示踪剂用于成像ROS/RNS介导的氧化应激。研制出放射性示踪剂 在研发中，3将在我们机构的动物模型中进行初步验证。在对目标敏感性进行验证之后 和-使用建议的方法在体内分子水平上的新PET示踪剂的特异性，tr&d3将 与CPS合作，验证并进一步优化该技术，以在特定疾病中广泛应用 申请。总体而言，这些PET示踪剂将提供新的成像资源来询问这些重要的 炎症中的生物标志物。 涉入

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