NUCLEAR DIAGNOSTIC METHODS FOR RENAL DISEASE

该项目的总体目标是改善放射性物质和 核成像方法用于检测各种肾脏疾病和 量化不同的肾功能。终末期肾病 糖尿病、免疫球病、艾滋病和其他疾病 现在需要透析或肾移植的人不仅仅是 美国有15万名患者，仅需要年度医疗保险福利 超过30亿美元。放射性核素定量成像 应该更多地利用肾脏来检测肾脏的早期下降 通过系列研究发挥作用，并监测药物和 其他治疗方案。 L-L-乙二半胱氨酸(EC)和p-硫代丙酮偶合物 合成了氨基马尿酸酯，并用TC-99m标记为 替代放射性碘标记邻碘马尿酸(OIH)定量测定 有效的肾脏血浆流量，并实现更好的空间分辨率 伽马相机的图像比用碘放射性核素要好。 溶菌酶将被放射性碘标记，并与螯合物偶联 用于~(99)Tc标记。这种低分子量(LMW)的蛋白质具有很高的 肾皮质的摄取并在那里分解代谢，几乎可以忽略不计 肝脏摄取。我们建议对肾脏的下降进行量化。 通过伽马相机成像确定24小时内的放射性 人大鼠模型中低分子蛋白质分解率的差异 疾病与对照组相比。 我们建议比较~(99m)Tc-EC、~(99m)Tc-~(99)m的疗效 硫代乙酰甘氨酸(MAG3)、~(99m)Tc-DTPA和~(131)I-OIH 肾动脉狭窄对肾血管性高血压的诊断价值 2肾一夹大鼠模型。这些研究将在之前和 在给予血管紧张素转换酶抑制剂卡托普利和依那普利拉后。 我们将评估三种不同治疗方案的疗效 改善肾功能先升后降的状态 在链脲佐菌素诱导的大鼠糖尿病中。肾小球滤过 速率将通过Tc-99m DTPA清除量进行连续监测。 我们将比较五种不同肾脏放射诊断的疗效。 急性肾小管轻度坏死(ATN)检测试剂 暂时夹住一条肾动脉。八种不同治疗方法 各国将就其防止单边ATN的能力进行比较。

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.