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.
