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

描述(申请人提供)：在拟议的研究项目中，将开发具有所需物理和生物特性的用于计算机断层扫描(CT)的候选TAO纳米造影剂，用于临床。我们开发了一种一流的两性氧化钽(TAO)纳米颗粒CT造影剂，专门设计用于大块头到肥胖患者的对比度增强CT成像。这些纳米粒具有临床制剂的近乎理想的物理化学性质，并在大鼠给药研究中表现出同等的生物学性能(器官保留和急性耐受性)。我们预计，在对这些患者群体进行成像时，辐射剂量至少会减少50%，同时产生的图像质量与商业上可获得的碘化造影剂相当或更好。目的1.开发安全实用的氧化钽纳米粒子用于临床-在我们之前基础研究的基础上，我们将通过改变粒子大小和壳层化学来开发新的两性离子TaO纳米粒子，以提高CT成像性能。我们将证明纳米粒子在生物上是安全的，并具有可与碘为基础的同类产品相媲美的器官滞留。目的2.确定特定于钽的CT成像协议，以在减少辐射剂量的情况下优化大到肥胖患者群体的图像质量。-我们将确定特定于钽的CT采集协议，以提供与基于碘的同行相比减少50%的辐射剂量时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上相关的拟人模型进行计算机模拟和体模实验，这些模型代表了不同的患者大小。目的3.在代表大到肥胖患者群体的猪动物模型中，证明在不损失诊断性能的情况下，提高了成像的安全性。-我们将使用模拟大到肥胖患者的猪动物模型来演示对比剂剂量和/或辐射剂量的减少(改进的成像安全性)。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.