NUCLEAR DIAGNOSTIC METHODS FOR RENAL DISEASE

该项目的目标是提高检测和表征 通过开发新的放射性试剂来治疗各种肾脏疾病 和新的非侵入性放射性同位素方法。他们将被评估 主要是在大鼠的人类肾脏疾病模型中与对照相比。 使用伽马照相机和专用计算机的现有临床技术 只能提供肾脏的定性图像， 肾小球滤过率（GFR）和有效肾血浆流量（ERPF）。 本项目将探索肾功能的其他方面。 止血异常被认为在这一过程中起重要作用。 几种重要肾脏疾病的进展，特别是糖尿病 和膜增生性肾小球肾炎。模型大鼠 这些人类疾病，我们将评估生存和肾脏吸收的 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”将阻止恶化 与未处理动物相比的肾功能。 我们计划开发的新放射性药物包括（1） 巯基乙酰基三甘氨酸（MAG_3）与Tc-99 m的螯合作用 对于I-131马尿酸，具有相当高的肾脏提取效率， (2)小的大分子如葡聚糖和溶菌酶， 阳离子聚乙烯亚胺或用Tc-99 m和In-111标记。我们将 探索这些阳离子大分子的应用， 肾小球基底正常阴离子电荷减少 膜（GBM），其在几种重要的肾脏疾病中早期发生。我们 将评估这些放射性标记的大分子在大鼠中的分布 这些人类疾病的模型与传统的肾脏 放射诊断剂，如Tc-99 m DTPA和I-131马尿酸。 我们建议研究肾脏的清除率和器官分布的改变， 白细胞介素-2诱导的肾前性氮质血症的放射诊断药物 大鼠由于异常的毛细渗透率和由此产生的流体 从血浆容量转移到血管外空间，常规 单次注射c-99 mDTPA和I-131测定GFR和ERPF 马普伦分别被认定无效。因此，这些代理人将 通过连续输注给予I-125， 给药以提供“毛细血管渗透性指数”， 主要器官放射性标记微球的脑室内注射 将被用来测量血液中的变化低到主要器官， 这种有毒的状态。 高、低摩尔浓度血管内造影的肾毒性 对比剂将在具有两种诱导肾损伤模型的大鼠中进行比较。 病变--单侧缺血和双侧肾小管功能障碍， 铂醇

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.