succimer and Acid-Base-Imbalance

Seventy female Sprague-Dawley rats were studied to determine the mechanism of tubular localization and the effects of commonly encountered changes in hydration and acid-base balance on renal uptake and urinary excretion of technetium-99m glucoheptonate ([99mTc]GHA). The in-vivo protein binding and protein-free plasma clearance of [99mTc]GHA also were quantitated. Twenty additional rats were studied to determine the effects of PAH competition and probenecid blockade on renal uptake of [99mTc]dimercaptosuccinic acid (DMSA) in comparison with their effects on [99mTc]GHA localization. Kidney uptake of [99mTc]GHA averaged 11.17 +/- 0.49 (s.e.)% of the injected dose in control animals. This varied slightly among groups but was significantly reduced by probenecid blockade and para-aminohippuric acid (PAH) competition to 4.08 +/- 0.55 (p less than 0.005) and 2.39 +/- 0.14 (p less than 0.005), respectively. Technetium-99m DMSA was not affected in its renal accumulation by these maneuvers. The total plasma clearance of [99mTc]GHA was lower than iodine-125(125I)iothalamate but the clearance of the protein free supernate was higher, raising a possibility of some tubular secretion. Acidification of the urine which has been shown to reduce [99mTc]DMSA uptake appeared to have no effect on [99mTc]GHA. Hepatic uptake was minimal in all groups averaging less than 1% injected dose. These data demonstrate that renal accumulation of [99mTc]GHA is blocked by probenecid and PAH suggesting that it is actively concentrated in the proximal tubule by enzyme systems similar to those involved in PAH and hippuran transport. It appears that [99mTc]GHA uptake measures a different aspect of kidney function than [99mTc]DMSA.

Topics: Acid-Base Imbalance; Animals; Female; Iodine Radioisotopes; Iothalamic Acid; Kidney; Organotechnetium Compounds; p-Aminohippuric Acid; Probenecid; Radionuclide Imaging; Rats; Rats, Inbred Strains; Succimer; Sugar Acids; Technetium; Technetium Tc 99m Dimercaptosuccinic Acid

Thirty-eight female Sprague-Dawley rats were studied to determine the effects of (a) tubular blockade and (b) commonly encountered changes in hydration and acid-base balance, on the urinary excretion and renal localization of Tc-99m dimercaptosuccinic acid (DMSA). Ten additional rats were studied to quantitate the in vivo protein binding of Tc-99m DMSA, and a final group of 12 animals was used to quantitate DMSA distribution in animals with diminished functional renal mass. Both osmotic diuresis and dehydration by water deprivation for 24 hr resulted in a plasma clearance of DMSA slower than in control animals. Acid-base imbalances significantly affected the renal accumulation of DMSA, and acidosis was associated with markedly increased background due to increased liver accumulation. The protein-bound portion of Tc-99m DMSA in the plasma was high, reaching 89% within the first 5 min, and rising very slightly (n.s.) ith time. The unbound portion of DMSA had a plasma clearance slightly higher than the GFR. Ablation of large amounts of renal tissue, resulting in significant decreases in GFR. Ablation of large amounts of renal tissue, resulting in significant decreases in GFR, did not significantly affect the renal localization of DMSA in the intact portions of the kidneys. These data demonstrate that commonly encountered changes in acid-base balance and hydration will significantly alter the biologic distribution of Tc-99m DMSA. These factors should be controlled when carrying out clinical studies.

Topics: Acid-Base Imbalance; Animals; Dehydration; Diuresis; Female; Glomerular Filtration Rate; Kidney; Protein Binding; Rats; Rats, Inbred Strains; Renal Circulation; Succimer; Sulfhydryl Compounds; Technetium; Technetium Tc 99m Dimercaptosuccinic Acid; Tissue Distribution