Radiological Image Enhancement with Tantalum, a Heavy Z Atom

描述(由申请人提供)：含有一个或多个重Z(高原子序数)原子的试剂在对比度和空间分辨率方面提供了实质性的改善，同时降低了患者的总辐射剂量。这项拟议的研究工作的目标是制备定义明确的钽化合物作为射线照相剂。几十年来，钽(Ta)一直被用作金属植入物和放射照相标记。主要重点将放在含有几个钽原子的簇合物上，从而使X射线具有较高的衰减能力。这些化合物将被合成、表征、修饰和筛选，以预测生理相容性的性质。理想的钽造影剂(1)提供高X射线衰减和高对比度，(2)在生理条件下稳定，(3)在高浓度下可用，(4)无毒，(5)易于注射，(6)停留在ROI(感兴趣区域)足够长的时间以允许成像，(7)然后完全从体内排泄。我们的假设是，可以利用钽作为重原子来开发合适的造影剂。含Ta材料的目标性能是(1)Ta致密的团簇，(2)充分可修饰的表面，以达到其他试剂的要求。有希望的试剂将被评价为饱和溶液，通过X射线吸收分析。背景信号确定将使得能够对集群表面系统进行排名。所需剂量情景将从稀释系列的分析中推断出来。在体外测试完成后，我们将继续进行第二阶段的动物试验，以表征体内的安全性和有效性。一旦这些被确定，我们将有望继续进行临床试验，从而导致这些药物被释放用于临床。与公众健康相关：拟议的钽簇可以显著改进X射线成像技术，作为一种替代造影剂，具有更好的对比度，从而实现更好的诊断成像。它们可以用更少的造影剂提供更好的成像，改善穿透深度和减少散射，从而降低图像噪声和减少辐射暴露。它们还可以为肥胖患者提供更好的成像，并为对碘过敏的患者提供一种替代造影剂。

DESCRIPTION (provided by applicant): Agents containing one or more heavy Z (high atomic number) atoms offer substantial improvements in contrast and spatial resolution, while reducing the overall patient radiation dose. The objective of this proposed research effort is to prepare well-defined tantalum compounds as radiographic agents. Tantalum (Ta) has been used for decades as both a metallic implant and radiographic marker. The principal focus will be on cluster compounds that contain several tantalum atoms, thus enabling high X-ray attenuation. These compounds will be synthesized, characterized, modified, and screened for properties predictive of physiological compatibility. The ideal tantalum-based contrast agent (1) provides high X-ray attenuation and therefore high contrast, (2) is stable under physiological conditions, (3) is available in high concentration, (4) is non- toxic, (5) is injected easily, (6) resides in the ROI (Region of Interest) for a sufficient length of time to allow imaging, and (7) is then completely excreted from the body. Our hypothesis is that suitable contrast agents can be developed using tantalum as the heavy atom. The targeted properties of the Ta-containing materials are (1) a tantalum-dense cluster, (2) sufficiently modifiable surface to attain the other agent requirements. Promising agents will be evaluated as saturated solutions by X-ray absorption analysis. Signal to background determination will enable a ranking of the cluster-surface systems. Required dose scenarios will be extrapolated from the analysis of dilution series. After the in vitro testing is completed we will proceed to Phase II with animal trials to characterize safety and efficacy in vivo. Once these are established, then we will hopefully continue with clinical trials that will lead to the release of the agents for clinical use in humans. PUBLIC HEALTH RELEVANCE: The proposed tantalum clusters may substantially improve X-ray imaging technology as an alternative contrast agent with improved contrast allowing superior diagnostic imaging. They can potentially provide better imaging with smaller quantities of contrast agent, improved depth of penetration and reduced scattering, resulting in lower image noise as well as reduced radiation exposure. They can also provide better imaging for obese patients and an alternative contrast agent for patients allergic to iodine.