Improved Renal Diagnoses using Gold Nanoparticle CT Imaging

描述（由申请人提供）：超过1000万美国人患有慢性肾病和肾癌，每年导致109，000人死亡，残疾人数是这个数字的许多倍。需要更好的方法来研究肾功能，检测和准确诊断病理。成像对泌尿学和肾脏学很重要，改进的功能性肾脏成像可以通过实现图像引导的诊断、程序、治疗和监测来改善医疗保健。不幸的是，所有的X射线造影剂（基于碘）都是肾毒性的，并且FDA已经发出警告，不鼓励对肾功能下降的人使用钆MRI成像，从而限制了CT和MRI的重要用途。我们已经发现，小的金纳米颗粒产生良好的血管放射成像，并迅速过滤的肾脏进入膀胱，从而产生泌尿系统的精致成像。初步毒性测试表明，它们在有用的水平上是无毒的。这些试剂具有与碘和钆试剂完全不同的化学性质，可能能够填补泌尿系统无创高分辨率成像的空白。初步测试显示出无与伦比的高分辨率功能性肾脏成像。在提出的工作中，将优化金纳米粒子，并在小鼠中与碘剂相比，评估其在受损肾脏中的安全性。将使用microCT证明急性肾小管坏死的检测。如果这项工作是成功的，这些新的造影剂可能会导致更早，更准确地检测肾脏病理，伴随着改善治疗和许多患者的结果。与公共卫生的相关性：我们最近开发了新的药物，使用纳米技术更好地成像肾功能。如果这项研究成功，这些新的药物可以更早，更准确地检测肾脏疾病，从而改善许多患者的治疗和预后。

DESCRIPTION (provided by applicant): Over 10 million Americans suffer from chronic kidney disease and kidney cancer, resulting in 109,000 deaths a year and disability to many times that number. Better methods to study renal function and detect and accurately diagnose pathology are needed. Imaging is important to urology and nephrology, and improved functional kidney imaging could improve health care by enabling image guided diagnoses, procedures, therapies, and monitoring. Unfortunately, all of the x-ray contrast agents (which are based on iodine) are nephrotoxic, and a FDA warning has been issued discouraging use of gadolinium MRI imaging for persons with decreased renal function, thus limiting the important usefulness of CT and MRI. We have found that small gold nanoparticles produce excellent radiographic imaging of blood vessels and are rapidly filtered by the kidneys into the bladder thus producing exquisite imaging of the urinary system. Initial toxicity tests show them to be non-toxic at useful levels. These agents have a completely different chemistry from iodine and gadolinium agents and may be able to fill the void in noninvasive high resolution imaging of the urinary system. Preliminary tests have shown unsurpassed high resolution functional kidney imaging. In the work proposed, gold nanoparticles will be optimized and their safety evaluated in compromised kidneys compared to iodine agents in mice. Detection of acute tubular necrosis will be demonstrated using microCT. If this work is successful, these novel contrast agents could lead to earlier and more accurate detection of renal pathology with concomitant improved treatments and outcomes for many patients. Relevance to Public Health: We have recently developed new agents to better image kidney function using nanotechnology. If this study is successful, these novel agents could lead to earlier and more accurate detection of kidney disorders resulting in improved treatments and outcomes for many patients.