Lung Imaging

 描述(申请人提供)：生物发光成像是一种简单而灵敏的方法，可以在活体小鼠身上观察疾病进展和对治疗药物的反应。生物发光在许多小鼠疾病模型中被常规应用，很少用于体内呼吸道和肺部的炎症过程的成像。限制BLI在肺和呼吸道成像中应用的根本因素是：天然荧光素酶底物D-荧光素进入肺和呼吸道的能力相对较差，来自深层组织的可见光波长光子的吸收和散射导致的信号衰减较强，以及缺乏合适的肺或呼吸道特异性荧光素酶报告。我们假设，这些问题可以通过合成的荧光素来克服，这种合成的荧光素具有更好的进入肺和呼吸道组织的药理作用，并在组织穿透近红外波长处发射光(目标1)，并通过使用仅在呼吸道表达的荧光素酶报告(目标2)。这些荧光素和荧光素酶记者将使我们能够研究感染和过敏性哮喘活体小鼠模型中基因表达的实时调节，极大地提高我们持续监测肺部疾病进展和治疗反应的能力。

 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.