NUCLEAR DIAGNOSTIC METHODS FOR RENAL DISEASE

该项目旨在改善各种检测和表征 通过开发新的放射性诊断剂， 方法. 使用伽马照相机和专用计算机的现有技术 只能提供肾脏的定性图像和 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。 待开发的新药剂包括：（1）Tc-99m类似物 巯基乙酰基三甘氨酸，具有高肾提取率，以替代I-131 用于ERPF测定的马尿酸，（2）阳离子小分子 用In-111或Tc-99m标记的葡聚糖，菊粉，以反映 恶化前肾小球膜的正常阴离子电荷 （3）用~（111）In或~（99m）Tc溶菌酶定量低GFR血症患者的血凝素 肾小管细胞的分子蛋白，和（4）标记的类似物 阳离子药物，比较其肾小管转运与 肾小管功能障碍模型中存在的放射性阴离子。 将这些新制剂的生物分布与常规制剂进行比较。 通过血浆清除率、尿排泄和 在正常大鼠、兔、狗和恒河猴中的连续相机成像。 大鼠中的详细器官分布将通过直接组织 在不同的时间间隔处死后进行测定。 标记阳离子小分子 大分子将试图检测阴离子肾小球的损失 链脲佐菌素诱导的大鼠糖尿病模型及 血管内碘化造影剂。 各种药剂的功效， 包括标记的溶菌酶，将在大鼠中进行比较，以检测 环孢素A和顺铂的肾毒性。 血管紧张素转换 将评价酶抑制剂（卡托普利和去酯化依那普利） 用于检测单侧肾血管性高血压，在注射 不同的放射诊断剂，在2肾，1夹大鼠模型。

This project seeks to improve the detection and characterization of various renal diseases by the development of new radioactive diagnostic agents and methods. Existing techniques using a gamma camera and dedicated computer can provide only qualitative images of the kidneys and estimates of glomerular filtration rates (GFR) and effective renal plasma flow (ERPF). This project will explore other aspects of renal function. The new agents to be developed include (1) analogues of Tc-99m mercaptoacetyltriglycine, with a high renal extraction to replace I-131 Hippuran for estimation of ERPF, (2) cationic small macromolecules (dextran, inulin) labeled with In-111 or Tc-99m to reflect alterations in the normal anionic charge of the glomerular membrane before deterioration of GFR, (3) In-111 or Tc-99m lysozyme for quantitation of catabolism of low molecular proteins by renal tubular cells, and (4) labeled analogues of cationic drugs to compare their renal tubular transport with that of existing radioactive anions in models of tubular dysfunction. The biodistribution of these new agents will be compared with conventional renal radiodiagnostic agents by plasma clearance, urinary excretion and serial camera imaging in normal rats, rabbits, dogs and Rhesus monkey. Detailed organ distribution in rats will be determined by direct tissue assay after sacrifice at various time intervals. Labeled cationic small macromolecules will be tried to detect the loss of anionic glomerular membrane charge in streptozotocin-induced diabetes in rats and after intravascular iodinated contrast media. The efficacy of various agents, including labeled lysozyme, will be compared in rats for the detection of nephrotoxicity from cyclosporin A and cisplatin. Angiotensin-converting enzyme inhibitors (captopril and de-esterified enalopril) will be evaluated for detecting unilateral renovascular hypertension, before the injection of different radiodiagnostic agents, in the 2-kidney, 1-clip rat model.