Nanoparticle CT Contrast Agents for Reduced Radiation Dose and New Imaging Applic

描述（由申请人提供）：在拟议的研究项目中，将开发用于计算机断层扫描（CT）的候选TaO纳米颗粒造影剂，该造影剂具有所需的物理和生物特性，可用于临床。我们开发了一种一流的氧化两性离子（TaO）纳米颗粒CT造影剂，专门用于大到肥胖患者的CT增强成像。这些纳米颗粒具有接近理想的物理化学性质，可用于临床配方，并在大鼠给药研究中显示出相当的生物性能（器官保留和急性耐受性）。我们预计在对该患者人群进行成像时，至少可以减少50%的辐射剂量，同时产生相当于或优于市售碘造影剂的图像质量。目的1。开发安全实用的氧化钽纳米颗粒用于最终的临床应用-在我们之前的基础研究的基础上，我们将通过改变颗粒大小和外壳化学来开发新的两性离子氧化钽纳米颗粒，以提高CT成像性能。我们将证明纳米颗粒在生物学上是安全的，并且具有与基于碘的对应物相当的器官保留。目标2。确定钽特异性CT成像方案，以优化大到肥胖患者群体在降低辐射剂量下的图像质量。-与基于碘的CT采集方案相比，我们将确定钽特异性CT采集方案，以减少50%的辐射剂量提供同等或改进的图像质量（更好的信噪比，减少伪影）。我们将使用简单的和解剖学相关的拟人化的幻影进行计算机模拟和幻影实验，这些幻影代表了广泛的患者尺寸。目标3。在猪动物模型中证明在不损失诊断性能的情况下提高了成像安全性，该模型代表了大到肥胖的患者群体。-我们将使用猪动物模型模拟肥胖患者，演示造影剂和/或辐射剂量的降低（提高成像安全性）。我们将描述诊断性能，使用的指标是成像信噪比的函数。

DESCRIPTION (provided by applicant): In the proposed research project, candidate TaO nanoparticle contrast agents for computed tomography (CT) will be developed with desired physical and biological properties for clinical use. We have developed a first-in-class zwitterioni tantalum oxide (TaO) nanoparticle CT contrast agent, specifically designed for contrast-enhanced CT imaging of large-to-obese patients. These nanoparticles have near-ideal physicochemical properties for clinical formulation and have shown equivalent biological performance (organ retention and acute tolerability) in rat dosing studies. We anticipate at least 50% radiation dose reduction when imaging this patient population, while producing image quality that is equivalent or better than what is provided with commercially-avail- able iodinated contrast agents. Aim 1. Develop tantalum oxide nanoparticles that are safe and practical for eventual clinical use -Building upon our previous foundational research, we will develop new zwitterionic TaO nanoparticles by modifying particle size and shell chemistry to benefit CT imaging performance. We will demonstrate that the nanoparticles are biologically safe and have organ retention that is comparable to iodine-based counterparts. Aim 2. Determine tantalum-specific CT imaging protocols to optimize image quality at reduced radiation dose for the large-to-obese patient population.-We will identify tantalum-specific CT acquisition protocols to provide equivalent or improved image quality (better signal-to-noise ratio, reduced artifacts) at 50% reduced radiation dose, when compared to iodine-based counterparts. We will perform computer simulations and phantom experiments using both simple and anatomically-relevant anthropomorphic phantoms, which represent a wide range of patient sizes. Aim 3. Demonstrate improved imaging safety without loss of diagnostic performance in a porcine animal model that is representative of the large-to-obese patient population. -We will demonstrate contrast dose and/or radiation dose reduction (improved imaging safety) using a porcine animal model mimicking large-to-obese patients. We will characterize diagnostic performance, using metrics that are a function of the imaging signal-to-noise ratio.