Animal evaluation of technetium-99m triamide mercaptide complexes as potential renal imaging agents.
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Technetium-99m mercaptoacetylglycylglycylglycine (MAG3), a [99mTc]triamide mercaptide (N3S) compound has been synthesized in an attempt to obviate the stereochemistry problems associated with the diamide dimercaptide (N2S2) ligands. Because initial studies have been promising, the terminal glycine on the MAG3 compound has been varied to create a new series of N3S compounds. Twelve new N3S complexes were initially screened in mice and the more promising complexes, 99mTc mercaptoacetylgylcylglycyl-glycine [( 99mTc]MAG3), 99mTc mercaptoacetylgylcylglycyl-L-alanine [( 99mTc]MAG2-Ala), and both complexes of 99mTc mercaptoeacetylglycylglycyl-L-asparagine [( 99mTc]MAG2-Asn) and 99mTc mercaptoacetylglycylglycyl-L-glutamine [( 99mTc]MAG2-Gln), were further evaluated in rats utilizing constant infusion blood clearances, extraction efficiencies and protein binding assays. The renal excretion of all these complexes compared favorably with simultaneously administered [131I]OIH and [125I]iothalamate. The triamide mercaptide complexes represent a new ligand class for 99mTc, which may provide a variety of complexes for the evaluation of renal tubular function. (+info)
Comparison of technetium-99m MAG3 kit with HPLC-purified technetium-99m MAG3 and OIH in rats.
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Technetium-99m (99mTc) mercaptoacetylglycylglycylyglycine (MAG3) in high (greater than or equal to 95%) radiochemical purity is prepared from lyophilized kits containing benzoylMAG3, sodium tartrate, lactose, and stannous chloride by adding sodium [99mTC]pertechnetate and heating the contents briefly. Constant-infusion renal whole-blood clearance obtained with [99mTc] MAG3 kits was compared with that obtained with high performance liquid chromatography (HPLC) pure [99mTc]MAG3 and with co-infused iodine-131 (131I) iodohippurate (OIH) in anesthetized rats. Average renal whole-blood clearance of [99mTc]MAG3 from kits was 3.9 +/- 0.4 ml/min/100 g body weight (mean +/- s.e.m. n = 5) and that for HPLC-pure [99mTc]MAG3 was 4.6 +/- 0.3 (n = 3). Renal whole-blood clearance ratios for [99mTc]MAG3 to co-infused iodine-131 (131I) OIH were greater than unity for both kit formulation (1.7 +/- 0.1) and HPLC-pure [99mTc]MAG3 (1.9 +/- 0.2). Differences in these two measures were not significant. Plasma binding (determined from blood drawn at the end of the infusion) of [99mTc]MAG3 prepared from both kits (75 +/- 2%, n = 4) and HPLC-separation (76 +/- 4%) were greater than that of [131I]OIH in corresponding plasma samples (31 +/- 1% and 32 +/- 2%) respectively). Renograms performed in anesthetized rats revealed no statistically significant differences between kit-prepared [99mTc]MAG3 and [131I]OIH in terms of time-to-peak renal activity (5.0 +/- 1.7 min, n = 6; and 2.2 +/- 0.2 min, n = 3, mean +/- s.e.m. for [99mTc]MAG3 and [131I]OIH, respectively), in terms of time to fall to half-maximal activity (15.3 +/- 2.4 min and 9.6 +/- 2.1 min, respectively), or in terms of fraction of peak radioactivity in right kidney (0.53 +/- 0.01 for both substances). To assess possible interference from hepatobiliary uptake and excretion in renal failure, radioactivity in liver regions of interest was followed by gamma camera scintigraphy for 30 min after intravenous injection of [131I]OIH and kit and HPLC-purified [99mTc]MAG3 in anesthetized rats rendered anephric by ligating renal peduncles. Liver activity was 25% of total for both preparations of [99mTc]MAG3 and was 22% of total for [131I]OIH. There were no significant differences among the substances. (+info)
Technetium-99m MAG3, a comparison with iodine-123 and iodine-131 orthoiodohippurate, in patients with renal disorders.
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A Phase I study in 12 patients with renal disorders compared the simultaneous clearances of 99mTc-labeled mercaptoacetyltriglycine (MAG3) and 131I-labeled orthoiodohippurate (OIH). The ratio of MAG3 to OIH clearance was 0.61 +/- 0.08 as a result of its smaller volume of distribution, ratio 0.65 +/- 0.09, for the clearance half-lives were similar, ratio 1.09 +/- 0.12. A Phase II study performed serially in 20 patients with equal doses of [99mTc]MAG3 and [123I]OIH gave images of equal quality. The relative renal functions were highly correlated (r = 0.97, p less than 0.001) and transit time analyses gave good correlations: parenchymal transit time index r = 0.81, p less than 0.05. We conclude that [99mTc]MAG3 has some advantages over [99mTc]DTPA and is a suitable replacement for [123I]hippuran in routine renal imaging, relative function, and transit time studies, but not for the accurate estimation of the renal plasma flow. (+info)
Comparison of technetium-99m MAG3 with iodine-131 hippuran by a simultaneous dual channel technique.
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Technetium-99m MAG3, a technetium-labeled analog of hippuran, was compared with [131I] hippuran using a simultaneous dual isotope study in 20 patients. The plasma clearance for MAG3 was lower than that of hippuran, but its plasma concentration was higher, resulting in similar rates of excretion and similar renal time-activity curves. Apart from better statistics with the technetium-labeled agent, there were no clinically significant differences in this group of patients. (+info)
Abnormal captopril renogram with a technetium-99m-labeled hippuran analog.
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A case of renovascular hypertension is presented in which the [131I]hippuran renogram was initially normal, but became strikingly abnormal upon administration of the angiotensin converting enzyme (ACE) inhibitor captopril. The patient presented with fibromuscular dysplasia of the renal arteries, which was shown by hippuran renography to be functionally significant on the right side. She became normotensive after angioplasty of the right renal artery. Hypertension recurred a year later, at which time the renogram was normal without captopril, but showed functionally significant left renal artery stenosis with captopril challenge. Both the conventional agent, [131I]hippuran, and an experimental new 99mTc-labeled hippuran analog, [99mTc]MAG3, were used. Angiography confirmed progression of disease on the left side, which was successfully treated by angioplasty. Functionally significant unilateral renal artery stenosis was thus demonstrated first on the right side and then, 1 yr later, on the left side, using hippuran and [99mTc]MAG3. Anatomic progression of disease was documented by angiography. (+info)
Quantitation of renal function with technetium-99m MAG3.
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The technetium-labeled hippuran analog [99mTc]MAG3 was compared with [131I]hippuran in 50 patients using a quantitative renal function protocol that includes: (a) estimation of effective renal plasma flow by a single-injection, single-sample plasma clearance method, (b) determination of relative function of right and left kidney from the initial count rate over each kidney, and (c) comparison of recovered urine activity with plasma disappearance. This protocol is suitable for routine clinical use, and, in fact, has been used heavily at our clinic for a number of years. By slight modification of the formulas, the results obtained with [99mTc]MAG3 agreed well with those using [131I]hippuran. We conclude that [99mTc]MAG3 can be substituted for [131I]hippuran in the quantitative protocol, with the better image quality and lower radiation dose (in abnormals) of a technetium-labeled agent. (+info)
Detection of diffuse glomerular lesions in rats: I. Comparisons of conventional radioactive agents.
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Conventional renal diagnostic agents, [131I]hippuran, [99mTc]glucoheptonate (GHA), and [99mTc] dimercaptosuccinate (DMS) were compared with [99mTc] or [111In] diethylenetriaminepentaacetic (DTPA) for the detection of glomerular damage in rats compared with controls. The glomerular lesions were induced by the i.v. injection of puromycin aminonucleoside (PA) 9 days before the radionuclide studies, a model of spontaneous "minimal change" glomerulonephritis in humans. Computer-generated early renal uptake of [99mTc]DTPA or GHA correlated with the glomerular filtration rate (GFR) quantitated by biexponential plasma clearance of DTPA administered by single i.v. injection. The early renal uptake of hippuran and DMS correlated poorly with GFR as assessed by DTPA clearance. However, the 2-hr renal retention of DMS correlated well with the DTPA clearance. None of the parameters measured with [131I]hippuran correlated well with DTPA clearance, probably because of decreased protein plasma binding of hippuran secondary to hypoproteinemia in this experimental model. It was concluded that none of these agents was superior to labeled DTPA for the detection of glomerular damage in this experimental model. (+info)
The pH-dependent influence of aminoglycoside antibiotics on iodohippurate accumulation in rabbit renal cortical slices.
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The effects of aminoglycoside antibiotics on 125I-hippurate (OIH) accumulation in rabbit renal cortical slices were assessed in vitro using incubation media with pH-values ranging from 6.4 to 8.4 and containing streptomycin, kanamycin, amikacin, gentamicin and tobramycin in concentrations ranging from 100 to 2,000 microgram base/ml. The aminoglycoside-induced inhibition of OIH accumulation was clearly pH-dependent and most pronounced at alkaline pH-values. At pH 6.4 and 7.4 the aminoglycosides had either no or only moderate effects on OIH accumulation, while all drugs produced a distinct depression in accumulation at pH 7.9 and 8.4. The microbiologically inert N-acetyl gentamicin had no influence on accumulation. The influence of aminoglycosides on OIH accumulation is probably related to the pKa-values of these drugs and implies the presence of free amino groups. (+info)