NUCLEAR DIAGNOSTIC METHODS FOR RENAL DISEASE

该项目的目标是改进检测和表征 通过开发新的放射性物质来防治各种肾脏疾病 和新的非侵入性放射性同位素方法。他们将接受评估 主要是在大鼠人类肾脏疾病模型中与对照组比较。 使用伽马相机和专用计算机的现有临床技术 只能提供肾脏和心脏的定性图像 肾小球滤过率(GFR)和有效肾血浆流量(ERPF)。 这个项目将探索肾功能的其他方面。 止血异常被认为在高血压的发病中起重要作用。 几种重要的肾脏疾病，特别是糖尿病的进展 膜增生性肾小球肾炎。在大鼠模型中 这些人类疾病，我们将评估存活和肾脏摄取 放射性标记的血小板并确定是否“抗血小板” 阿司匹林和潘生丁的“治疗”将阻止病情恶化 肾功能与未经治疗的动物进行比较。 我们计划开发的新放射性药物包括(1)类似物 ~(99m)Tc3与巯基乙酰甘氨酸(MAG3)的络合作用 对于I-131河马具有相当高的肾脏提取效率和 (2)葡聚糖、溶菌酶等小分子偶联 阳离子聚乙烯亚胺或用~(99)Tc和~(111)In标记。我们会 探索这些阳离子大分子的应用来演示 肾小球基底区正常阴离子电荷的减少 膜(GBM)，早期出现在几种重要的肾脏疾病中。我们 将评估这些放射性标记的大分子在大鼠体内的分布 这些人类疾病的模型与传统肾脏的比较 放射诊断剂，如~(99m)Tc-DTPA和~(131)I马尿酸。 我们建议研究肾脏清除和器官分布的改变。 放射诊断剂治疗白介素2诱导的肾前性氮质血症 老鼠。由于异常的毛细血管渗透性和由此产生的液体 从血浆容量到血管外空间的转变，常规 C-99mDTPA和I-131单次注射测定肾小球滤过率和肾小球滤过率 河马分别被宣布无效。因此，这些特工将是 持续输注和I-125白蛋白 用来提供“毛细血管渗透性指数” 主要器官。脑室注射放射性标记微球 将用来测量血液中向下至主要脏器的变化 这种有毒状态。 高、低摩尔浓度血管内造影对肾脏的毒性 造影剂将在两种诱导肾模型的大鼠中进行比较 损害--单侧缺血和双侧肾小管功能障碍 普拉蒂诺。

The goal of this project is to improve the detection and characterization of various renal diseases by the development of new radioactive agents and new non-invasive radioisotopic methods. They will be evaluated chiefly in models of human renal diseases in rats compared with controls. Existing clinical techniques using a gamma camera and dedicated computer can provide only qualitative images of the kidneys and stimates of glomerular filtration rates (GFR) and effective renal plasma flow (ERPF). This project will explore other aspects of renal function. Hemostatic abnormalities are thought to play an important role in the progression of several important renal diseases, particularly diabetes mellitus and membranoroliferative glomerulonephritis. In rat models of these human diseases, we will assess the survival and renal uptake of radiolabeled platelets and determine whether or not "antiplatelet therapy" with aspirin and dipyridamole will arrest the deterioration renal function compared with untreated animals. New radiopharmaceuticals we plan to develop include (1) analogs of mercaptoacetyltriglycine (MAG3) for chelation with Tc-99m as a substitute for I-131 hippuran with a comparable high renal extraction efficiency and (2) small macromolecules such as dextran and lysozyme coupled with cationic polyethyleneimines or labeling with Tc-99m and In-111. We will explore the application of these cationic macromolecules to demonstrate the decrease in the normal anionic charge of the glomerular basement membrane (GBM) which occurs early in several important renal diseases. We will assess the distribution of these radiolabeled macromolecules in rat models of these human diseases compared with conventional renal radiodiagnostic agents such as Tc-99m DTPA and I-131 hippuran. We propose to study the altered clearance and organ distribution of renal adiodiagnostic agents in pre-renal azotemia induced by interleukin-2 in rats. Because of the abnormal capillary permeability and resultant fluid shift from plasma volume to extravascular spaces, conventional measurements of GFR and ERPF by single injection of c-99m DTPA and I-131 hippuran respectively are rendered invalid. Hence, these agents will be administered by continuous infusion and I-125 albumin will be administered to provide an "index of capillary permeability" for the major organs. Intraventricular injections of radiolabeled microspheres will be used to measure the changes in blood low to the major organs in this toxic state. The nephrotoxicity of high- and low-molality intravascular radiographic contrast media will be compared in rats with two models of induced renal lesions--unilateral ischemia, and bilateral tubular dysfunction induced wit platinol.