Lung Imaging

 描述（由申请人提供）：生物发光成像是一种简单而灵敏的方法，可在活小鼠中观察疾病进展和对治疗剂的反应。尽管在许多小鼠疾病模型中应用，但生物发光很少用于体内气道和肺部的炎症过程成像。限制BLI应用于肺和气道成像的基本因素是天然荧光素酶底物D-荧光素进入肺和气道的能力相对较差，由于吸收和散射来自深部组织的可见波长光子导致的强信号衰减，以及缺乏合适的肺或气道特异性荧光素酶报告基因。我们假设，这些问题可以通过合成的荧光素酶来克服，所述合成的荧光素酶表现出对肺和气道组织的改善的药理学接近性，并发射组织穿透近红外波长的光（Aim 1），并且通过使用荧光素酶报告基因来克服，所述荧光素酶报告基因的表达限于气道（Aim 2）。这些荧光素酶和荧光素酶报告基因将使我们能够在感染和过敏性哮喘的活小鼠模型中研究基因表达的实时调控，大大提高我们持续监测肺部疾病进展和对治疗药物反应的能力。

 DESCRIPTION (provided by applicant): Bioluminescence imaging is a simple and sensitive method to visualize disease progression and response to therapeutics in live mice. Routinely applied in many mouse disease models, bioluminescence is rarely used for imaging inflammatory processes of the airways and lungs in vivo. The fundamental factors limiting the application of BLI for lung and airway imaging are the relatively poor ability of the natural firefy luciferase substrate D-luciferin to access the lung and airways, strong signal attenuation due to absorption and scattering of visible-wavelength photons originating from deep tissues, and the lack of suitable lung or airway-specific luciferase reporters. We hypothesize that these problems can be overcome by synthetic luciferins that exhibit improved pharmacological access to lung and airway tissues and emit light at tissue- penetrating near-infrared wavelengths (Aim 1), and through the use of luciferase reporters whose expression is restricted to the airways (Aim 2). These luciferins and luciferase reporters will enable us to study the real-time regulation of gene expression in live mouse models of infections and allergic asthma, greatly improving our ability to continually monitor disease progression in the lung and response to therapeutics.