succimer and maleic-acid

To elucidate renal leak of 99mTc-dimercaptosuccinic acid (99mTc-DMSA) in maleate-treated rats, plasma amino acid levels and urinary excreted % doses of 99mTc-DMSA and 131I-ortho-iodohippurate (131I-OIH) were studied by factor analysis. 0.4 m mol of Na-maleate dissolved in 2 ml of saline was intraperitoneally injected twice at an interval of 20 hours. Four hours later after second injection, mixture of 99mTc-DMSA and 131I-OIH was injected from tail vein. Urine was collected 15 minutes later to calculate the excretion ratios. Then rats were sacrificed by decapitation and blood samples were taken by cardiac puncture to determine plasma levels of amino acids and their metabolites. Urinary excreted % doses of 99mTc-DMSA were 10.1 +/- 1.3% in control group (n = 5) and 10.6 +/- 4.9% in maleate-treated group (n = 10). Of the 10 treated rats, only 2 rats showed clearly increased excretion of 99mTc-DMSA (19.1% and 19.4% respectively and others ranged from 6.2% to 12.0%). Fifteen variables used for factor analysis consisted of the % doses of two kinds of radiopharmaceuticals and 13 kinds of the data of amino acids analysis. Statistical procedures were as follows. Varimax rotation was performed, two factors were extracted and factor scores for each rat were plotted to obtain scattergram. Interpretation of the results led to a hypothesis that renal leak of 99mTc-DMSA might be relevant to decreased glutamine metabolism.

Topics: Animals; Factor Analysis, Statistical; Iodine Radioisotopes; Iodohippuric Acid; Kidney; Male; Maleates; Organotechnetium Compounds; Rats; Rats, Inbred Strains; Succimer; Sulfhydryl Compounds; Technetium Tc 99m Dimercaptosuccinic Acid

The renal handling of technetium-99m dimercaptosuccinic acid ([99mTc]DMSA) was studied in rats before and after treatment with Na-maleate (2 mmol/kg i.v.). In the control period, when measured 2 hr after the intravenous injection of [99mTc]DMSA, 39.9% of the injected dose was in the kidneys and 14.6% was in the bladder. After Na-maleate treatment, only 6.4% of the injected dose of [99mTc]DMSA was retained in the kidneys while 37.9% was found in the bladder. Subsequent studies revealed that Na-maleate produced a fall in the glomerular filtration rate, the effective renal plasma flow, and a generalized proximal tubular dysfunction. The latter was characterized by polyuria and an increased excretion of glucose, protein, albumin, calcium, and inorganic phosphate. It was concluded that proximal tubular dysfunction markedly alters the renal handling of [99mTc]DMSA. Whether this augmented urinary excretion is due to an inhibition of reabsorption or an enhanced cellular efflux of [99mTc]DMSA remains to be answered.

Topics: Animals; Fanconi Syndrome; Glomerular Filtration Rate; Kidney; Male; Maleates; Radionuclide Imaging; Rats; Rats, Inbred Strains; Renal Circulation; Succimer; Sulfhydryl Compounds; Technetium; Technetium Tc 99m Dimercaptosuccinic Acid