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脏疾病和肾癌，每年导致109000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。成像对泌尿科和肾脏病学很重要，改善功能性肾脏成像可以通过图像引导诊断、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（以碘为基础）都有肾毒性，FDA警告不鼓励肾功能下降的人使用钆磁共振成像，从而限制了CT和MRI的重要作用。我们发现细小的金纳米颗粒能产生出色的血管放射成像，并能迅速通过肾脏过滤进入膀胱，从而产生精细的泌尿系统成像。最初的毒性测试表明，它们在有用的水平上是无毒的。这些试剂与碘和钆试剂具有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。在这项工作中，金纳米颗粒将被优化，并与碘剂在小鼠体内受损肾脏中的安全性进行比较。显微ct将显示急性肾小管坏死的检测。如果这项工作取得成功，这些新型造影剂可以更早、更准确地检测肾脏病理，同时改善许多患者的治疗和预后。与公共卫生相关：我们最近开发了新的药物，利用纳米技术更好地成像肾脏功能。如果这项研究成功，这些新型药物可以更早、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.