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，将开发具有临床使用所需物理和生物学特性的计算机断层扫描（CT）候选TaO纳米颗粒造影剂。我们开发了一种一流的两性氧化钽（TaO）纳米粒子CT造影剂，专门设计用于大型至肥胖患者的对比增强CT成像。这些纳米颗粒具有接近理想的临床制剂的物理化学性质，并在大鼠给药研究中显示出等效的生物学性能（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，辐射剂量至少减少50%，同时产生的图像质量等于或优于市售碘化造影剂。目标1。开发安全实用的钽氧化物纳米颗粒，用于最终的临床应用-在我们以前的基础研究的基础上，我们将通过修改粒度和壳化学来开发新的两性离子TaO纳米颗粒，以提高CT成像性能。我们将证明纳米颗粒是生物安全的，并且具有与碘基对应物相当的器官保留。目标2.确定钽特异性CT成像协议，以优化图像质量，降低辐射剂量，适用于肥胖患者人群。我们将确定钽特异性CT采集协议，与碘基同行相比，在辐射剂量减少50%的情况下提供等同或改善的图像质量（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模型进行计算机模拟和模型实验，这些模型代表了各种各样的患者尺寸。目标3.证明在猪动物模型（代表大体型至肥胖患者人群）中提高成像安全性，而不损失诊断性能。- 我们将使用模拟大型至肥胖患者的猪动物模型来证明造影剂剂量和/或辐射剂量降低（改善的成像安全性）。我们将使用作为成像信噪比函数的指标来表征诊断性能。

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.