NUCLEAR DIAGNOSTIC METHODS FOR RENAL DISEASE

该项目的总体目标是改进放射性制剂， 用于检测各种肾脏疾病的核成像方法， 不同肾功能的量化。 终末期肾病 糖尿病、免疫球蛋白病、艾滋病和其他疾病 现在需要透析或肾移植的患者 美国有15万名患者，只需要每年的医疗保险福利 超过30亿美元。 放射性核素定量显像 肾脏应该更多地用于检测肾功能的早期下降， 通过系列研究发挥作用，并监测药物的疗效， 其他治疗方法。 L-L-亚乙基二半胱氨酸（EC）和p- 氨基马尿酸将被合成并用TC-99 m标记， 替代放射性碘化邻碘马尿酸盐（OIH）， 有效的肾血浆流量，并实现更好的空间分辨率 伽马照相机图像比碘放射性核素。 溶菌酶将用放射性碘标记并与螯合物结合 用于Tc-99 m标记。 这种低分子量（LMW）蛋白质具有很高的 在肾皮质中摄取并在那里分解代谢， 肝摄取 我们建议量化肾功能的下降， 放射性超过24小时，通过伽马照相机成像来确定 大鼠模型中低分子量蛋白的分解代谢率差异 与对照组相比。 我们建议比较Tc-99 m EC、Tc-99 m 巯基乙酰基三甘氨酸（MAG 3）、Tc-99 m DTPA和I-131 OIH 肾动脉狭窄对肾血管性高血压的检测 2肾1夹大鼠模型。 这些研究将在 在施用ACE抑制剂卡托普利和依那普利拉之后。 我们将评估三种不同治疗方案的疗效， 改善肾功能的初始增加和随后的降低 链脲佐菌素诱导的大鼠糖尿病。 肾小球滤过 将通过Tc-99 m DTPA清除率连续监测速率。 我们将比较五种不同的肾脏放射诊断方法的疗效。 用于检测由以下引起的轻度急性肾小管坏死（ATN）的试剂 暂时夹闭一侧肾动脉 八种不同的治疗 制度将比较他们的能力，以防止单边ATN。

The overall goal of this project is to improve the radioactive agents and nuclear imaging methods for the detection of various renal diseases and quantification of different renal functions. End-stage renal disease from diabetes, immunoglomerulopathies, AIDS, and other conditions requiring dialysis or renal transplantation now involves more that 150,000 patients in the U.S., requiring annual Medicare benefits alone exceeding 3 billion dollars. Quantitative radionuclide imaging of the kidneys should be exploited more for detecting early declines in renal function by serial studies, and to monitor the efficacy of drugs and other treatment regimes. L-L-ethylenedicysteine (EC) and a thiolacetone conjugate of p- aminohippurate will be synthesized and labeled with TC-99m as a substitute for radioiodinated o-iodohippurate (OIH) for quantitation of effective renal plasma flow and to achieve better spatial resolution in gamma camera images than with iodine radionuclides. Lysozyme will be labeled with radioiodine and conjugated with chelates for Tc-99m labeling. This low-molecular weight (LMW) protein has a high uptake in the renal cortex and is catabolized there, with negligible hepatic uptake. We propose to quantitate the decline in renal radioactivity over 24 hours by gamma camera imaging to determine differences in catabolic rate of LMW proteins in rat models of human disease compared with controls. We propose to compare the efficacy of the Tc-99m EC, Tc-99m mercaptoacetyltriglycine (MAG3), Tc-99m DTPA, and I-131 OIH for the detection of renovascular hypertension from renal artery stenosis in the 2 kidney-1 clip rat model. The studies will be performed before and after administration of the ACE inhibitors captopril and enaloprilat. We will evaluate the efficacy of three different treatment regimens for ameliorating the initial increase and later decrease in renal function in streptozotocin-induced diabetes in rats. The glomerular filtration rate will be monitored serially by Tc-99m DTPA clearances. We will compare the efficacy of five different renal radiodiagnostic agents for the detection of mild acute tubular necrosis (ATN) induced by temporary clamping of one renal artery. Eight different treatment regimes will be compared for their ability to prevent the unilateral ATN.