Comparison of iodine-131 OIH and technetium-99m MAG3 renal imaging in volunteers

Animal studies have suggested that the nonisomeric N3S triamide mercaptide ligand, 99mTc mercaptoacetyltriglycine (MAG3), may provide a satisfactory 99mTc-labeled replacement for 131I hippurate (OIH). Sequential 30-min [99mTc]MAG3 (5-10 mCi) and [131I]OIH (300 microCi) imaging studies were performed in ten normal volunteers in order to compare the image quality, renal excretion, blood clearance, and time to peak height of the renogram curve. In addition, [99mTc] MAG3 (5 mCi) and [131I]OIH (150 microCi) were administered simultaneously in eight volunteers for comparison of 180-min blood and plasma clearances and urine excretion. In the sequential imaging studies, the blood clearance of [99mTc]MAG3 was more rapid than [131I]OIH with a mean clearance of 1.30 l/min compared with 0.88 l/min for [131I]OIH (p less than 0.05). Seventy-three percent of the injected dose of the MAG3 was excreted by 30 min compared with 66.8% for [131I]OIH. Whole kidney and cortical renogram curves showed no significant difference in the time to peak height for MAG3 and [131I]OIH. In all subjects, the quality of the [99mTc]MAG3 images were clearly superior to [131I]OIH. Following simultaneous injection, blood and plasma clearances for [131I]OIH were more rapid than MAG3 when determined for multiple time intervals from 0-30 to 0-180 min (p less than or equal to 0.05). The 0-30-min clearances of MAG3 and [131I]OIH were only slightly greater than the 0-180-min clearances and can be used to obtain valid comparisons of the two agents. As in the sequential study, 30-min urine excretion was greater for MAG3 than [131I]OIH (73.1 compared with 69.6%) but the difference was not statistically significant. Although the differences in the MAG3 clearances following sequential and simultaneous administration are not satisfactorily explained, the fact that both clearances were rapid, the MAG3 and OIH renogram curves were quite similar, and 30-min urine excretions of MAG3 and OIH were essentially identical suggests that MAG3 may become a 99mTc replacement for [13I]OIH and further clinical evaluation is warranted.     

99mTc renal tubular function agents: current status

Orthoiodohippuric (OIH) acid labeled with 131I is a widely used renal radiopharmaceutical agent and has been the standard radiopharmaceutical agent for the measurement of effective renal plasma flow (EPRF). Limitations to the routine clinical use of 131I OIH are related to the suboptimal imaging properties of the 131I radionuclide and its relatively high radiation dose. 123I has been substituted for 131I; however, its high cost and short shelf-life have limited its widespread use. Recent work has centered on the development of a new 99mTc renal tubular function agent, which would use the optimal radionuclidic properties and availability of 99mTc and combine the clinical information provided by OIH. The search for a suitable 99mTc renal tubular function agent has focused on the diamide dithiolate (N2S2), the paraaminohippuric iminodiacetic acid (PAHIDA), and the triamide mercaptide (N3S) donor ligand systems. To date, the most promising 99mTc tubular function agent is the N3S complex: 99mTc mercaptoacetyltriglycine (99mTc MAG3). Studies in animal models in diuresis, dehydration, acid or base imbalance, ischemia, and renal artery stenosis demonstrate that 99mTc MAG3 behaves similarly to 131I OIH. A simple kit formulation is available that yields the 99mTc MAG3 complex in high radiochemical purity. Studies in normal subjects and patients indicate that 99mTc MAG3 is an excellent 99mTc renal tubular agent, but its plasma clearance is only 50% to 60% that of OIH. In an effort to develop an improved 99mTc renal tubular function agent, changes have been made in the core N3S donor ligand system, but to date no agent has been synthesized that is clinically superior to 99mTc MAG3.     

Technetium-99m MAG3, a comparison with iodine-123 and iodine-131 orthoiodohippurate, in patients with renal disorders

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.     

Comparison of technetium-99m MAG3 kit with HPLC-purified technetium-99m MAG3 and OIH in rats

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.     

Effects of altered physiologic states on clearance and biodistribution of technetium-99m MAG3, iodine-131 OIH, and iodine-125 iothalamate

Technetium-99m mercaptoacetyltriglycine [( 99mTc]MAG3) is a new renal radiopharmaceutical with biologic properties similar to iodine-131 orthoiodohippuric acid [( 131I]OIH). MAG3 may be used as a replacement for [131I]OIH and/or [99mTc]DTPA. For this reason, we compared the effects of several potential adverse clinical conditions on the clearance and biodistribution of MAG3, OIH and a GFR marker. To simulate renal failure, five mice underwent bilateral renal pedical ligation. Twenty-four hours after surgery they were injected with MAG3 and OIH and killed 2 hr postinjection. Compared to sham operated controls, liver activity for MAG3 and OIH increased from 0.2% to 14.1% and 0.1% to 13.9%, respectively, while intestinal activity increased from 1.3% to 8.9% for MAG3 and 0.2% to 7.7% for OIH. Constant infusion studies were performed in rats to evaluate the effects of increased plasma organic acid levels, mannitol diuresis, dehydration, and acid/base imbalance on the clearance of OIH, MAG3, and [125I]iothalamate. No differences were noted between the OIH and MAG3 clearances following diuresis and dehydration and the differences involving acid/base imbalance were minimal. Dehydration depressed the clearance of [125I]iothalamate more than that of OIH or MAG3. Para-aminohippurate (PAH) infusion inhibited the clearance of MAG3 more than OIH supporting proximal tubular transport for MAG3; PAH had no effect on [125I]iothalamate. In summary HPLC purified MAG3 behaved similarly to OIH under adverse physiologic conditions and the data continue to support the use of MAG3 as a potential clinical substitute for OIH.     

Synthesis and biological evaluation of technetium-99m MAG3 as a hippuran replacement

A new technetium-chelating agent based on a triamide monomercaptide tetradentate set of donor groups, mercaptoacetylglycylglycylglycine (MAG3), was synthesized and evaluated. Chelation with 99mTc resulted in a single radiochemical product as expected. Studies in mice of [99mTc]MAG3 indicated excretion rates faster than omicron-iodohippurate (OIH) both in normal and in probenecid treated animals. Specificity for renal excretion was essentially complete. Clearance studies in rats resulted in 2.84 ml/min/100 g for [99mTc]MAG3, 2.17 for OIH, and 1.29 for [125I]iothalamate. Extraction efficiencies were 85% for [99mTc]MAG3, 69% for OIH and 39% for [125I]iothalamate. Probenicid depressed the clearance both of [99mTc]MAG3 and OIH at 25 and 50 mg/kg/hr, but to a greater extent with [99mTc]MAG3. The greater effect is offset, however, by the larger fraction secreted by the renal tubular cells. The animal results suggest that [99mTc]MAG3 may be a useful alternative to [131I]OIH.     

Technetium-99m MAG-3 clearances after captopril in experimental renovascular hypertension

Rats with one kidney clamped (2K1C), both kidneys clamped (2K2C), unilaterally nephrectomized with remaining kidney clamped (1K1C), and normals, were studied using 99mTc mercaptoacetyltriglycine ([ 99mTc]MAG-3) and 131I orthoiodohippurate ([131I]OIH). Clearances of [99mTc]MAG-3 and [131I]OIH were performed after constricted rats became hypertensive. Clearances were repeated after i.v. Captopril. Clearances of [99mTc]MAG-3 and [131I]OIH in normals didn't change significantly after Captopril. Clearances of [99mTc]MAG-3 and [131I]OIH decreased insignificantly after Captopril in the 2K2C model. in the 2K1C group, normal kidney clearance increased ([99mTc]MAG-3 p less than 0.01 and [131I]OIH p less than 0.025) and clamped kidney clearance decreased after inhibition ([99mTc]MAG-3, p less than 0.01, [131I]OIH p less than 0.02). Clearances increased in the 1K1C group after Captopril ([99mTc]MAG-3 p less than 0.0025 and [131I]OIH, p less than 0.001). The ratio of [99mTc]MAG-3 to [131I]OIH before Captopril was 0.81 and 0.84 after Captopril. Changes in renal function after Captopril depend on the model of renovascular hypertension and possibly the dose administered. Technetium-99m MAG-3 clearance parallels [131I]orthoiodohippurate in renovascular hypertension.     

Animal evaluation of technetium-99m triamide mercaptide complexes as potential renal imaging agents

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.     

Quantitation of renal function with technetium-99m MAG3

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.     

A comparative evaluation of iodine-131 OIH and technetium-99m MAG3 in the study of renal function

A new renal imaging agent, 99mTc mercaptoacetyltriglycine (MAG3), has been recently proposed in the nuclear medicine evaluation of renal function. Just like 131 orthoiodohippurate (OIH), 99mTc MAG3 is removed mainly by the renal tubules. An heterogeneous group of 39 patients underwent a radioisotopic study with the simultaneous injection of OIH (131I) and 99mTc MAG3. Image quality was found to be better with 99mTc MAG3 than with OIH (131I), because the former always allowed renal regions of interest (ROI) to be clearly demonstrated, even in case of severe renal impairment. A quantitative analysis was also carried out: effective renal plasma flow (ERPF) values were compared with renographic peak times evaluated by using both radiotracers. Our results demonstrate a firm correlation to exist between the informative content yielded by 99mTc MAG3 and by OIH (131I). Absolute ERPF value was higher with MAG3, but the correlation index (r = 0.98) allowed a simple correction factor to be introduced. In conclusion, MAG3 appears to be a good alternative to OIH.     

Evaluation of the renal clearance of technetium-99m PAHIDA in dogs

The renal clearance of the technetium-99m complex of para[(biscarboxylmethyl)-aminomethylcarboxyamino]hippuric acid ([99mTc]PAHIDA), has been previously studied in rodents and falls between that of [99mTc]DTPA (diethylenetriaminepentaacetic acid) and iodine-131 (131I) orthoiodohippuran (OIH). To investigate the effect of species variation, the plasma clearance of [99mTc]PAHIDA was investigated in dogs. The plasma disappearance of the renal agent approached that of [99mTc]DTPA and was significantly less than that of OIH. Despite the structural similarities of the PAHIDA ligand and aminohippurate, the [99mTc]PAHIDA complex undergoes little, if any, tubular secretion in the canine kidney.     

Estimation of technetium-99m-MAG3 plasma clearance in adults from one or two blood samples

Technetium-99m mercaptoacetyltriglycine (MAG3) clearance is strongly correlated with effective renal plasma flow and can be used directly as a measure of renal function. For these reasons, formulas were developed for estimation of [99mTc]MAG3 clearance based on one or two plasma samples. A two-exponential model provided an excellent fit for 8-point plasma clearance curves obtained from 35 patients having a wide range of renal function. The 8-point [99mTc]MAG3 clearance could be estimated from a single point at 43 min with an error of 19 ml/min (residual s.d.) or from two samples at 12 and 94 min with an error of 7 ml/min. The relative errors with MAG3 are thus comparable to those reported for similar techniques used with [131I]orthoiodohippurate, [99mTc]diethylenetriaminepentraacetic acid and [51Cr]ethylenediaminetetraacetic acid.     

A comparative study of renal scintigraphy and clearance with technetium-99m-MAG3 and iodine-123-hippurate in patients with renal disorders

The aim of this study was to compare kit prepared technetium-99m-mercaptoacetyltriglycine (99mTc-MAG3) with our routine radiopharmaceutical, iodine-123-hippurate our routine radiopharmaceutical, iodine-123-hippurate ([123I]OIH) for renal dynamic scintigraphy. Seventeen patients with different nephrologic disorders or hypertension were first studied with OIH and then reinvestigated with MAG3 2-8 days later. Renal MAG3 gamma camera images were almost identical with those of OIH except for higher (p less than 0.01) liver-to-background ratios at 20 min postinjection, irrespective of kidney function. Urinary peristalsis was visible longer and more clearly in the MAG3 studies. MAG3 and OIH renograms showed identical relative kidney uptake (r = 0.99), but elimination of MAG3 from the kidneys was slower (p less than 0.01). The plasma clearance of MAG3 was lower than that of OIH, but correlated (r = 0.92) significantly. The plasma distribution volume and content in blood cells was lower (p less than 0.01), but the binding of MAG3 to plasma proteins was higher, 90%, as compared with 74% for OIH, p less than 0.01. Urinary excretion expressed as a percent of the given dose 60 min after injection was the same for the two substances. Thus, there are some significant differences in the renal handling, plasma distribution, and cell penetration between MAG3 and [123I]OIH. MAG3, however, seems to have particular qualifications as a radionuclide for dynamic renal scintigraphy, especially in patients who require acute investigations or in those with low renal function.     

Technetium-99m ethylene dicysteine: a new renal tubular function agent

Technetium-99m ethylene dicysteine (EC), a metabolite of ethylene cysteine dimer (ECD), is a new technetium-labelled renal tubular function tracer introduced as an alternative to ortho-iodohippurate (OIH) and with imaging qualities similar to 99mTc-mercaptoacetyltriglycine (MAG3). The elimination of 99mTc-EC is principally via active tubular transport. It is available in lyophilised kit form which can be easily prepared at room temperature, and the compound remains stable for at least 8 h. Both in normal individuals and in patients, plasma clearance of 99mTc-EC has been reported to be around 0.75 of OIH clearance. Thus there is a very strict correlation between 99mTc-EC and OIH clearance, and several algorithms are available to estimate OIH clearance from 99mTc-EC clearance. The renal extraction ratio of 99mTc-EC is 0.70. The distribution volume of 99mTc-EC is twice that of 99mTc-MAG3 (20% of body weight) and slightly higher than that of OIH. The plasma protein-bound fraction of 99mTc-EC (30%) is significantly lower than that of 99mTc-MAG3 and OIH. The same applies to red blood cell binding of 99mTc-EC (5.7%). There is negligible uptake in the liver and intestines. Within 1 h 70% of 99mTc-EC is excreted in the urine. 99mTc-EC provides the same scintigraphic information as 99mTc-MAG3. The lower liver activity makes 99mTc-EC particularly attractive in patients with renal failure. The 99mTc-EC clearance can be accurately estimated from a single plasma sample obtained at 54 min after injection. In conclusion, 99mTc-EC is a suitable renal imaging agent and for some applications is even more attractive than OIH: it provides an index of tubular function and yields high-quality images. The labelling procedure is easy, radiochemical purity is high and the complex is stable for a long time. The extent to which 99mTc-EC is adopted for clinical use will ultimately depend upon its cost and availability.     

Comparison of 99mTc-mercaptoacetyltriglycine and [131I]-o-iodohippurate elimination in perfused rat kidney

Renal elimination of two renal radiodiagnostic agents, (99m)Tc-mercaptoacetyltriglycine ((99m)Tc-MAG3) and [(131)I]-o-iodohippurate (OIH) has been studied using the method of the perfused rat kidney. The experiments showed significant differences between renal handling of (99m)Tc-MAG3 and OIH in the perfused rat kidney. While the renal clearance for (99m)Tc-MAG3 was relatively stable, the renal clearance values of OIH rapidly decreased after the OIH administration in a bolus dose. The infusion administration of OIH resulted in stable clearance values during the perfusion. The OIH/(99m)Tc-MAG3 renal clearance ratio was 2.47. Both compounds were bound to proteins in the perfusate to a considerable extent. An analysis of renal handling showed that contribution of tubular secretion to the total excretion was 95% for OIH, and 97% for (99m)Tc-MAG3.     

99mTc-MAG3 versus 131I-orthoiodohippurate in the routine determination of effective renal plasma flow

99mTc-mercaptoacetyltriglycine (MAG3) has been proposed as an alternative to 131I-orthoiodohippurate (OIH) for the scintigraphic determination of effective renal plasma flow (ERPF). The purpose of this study was to compare the ERPF values determined simultaneously with MAG3 and OIH by a dual channel technique in a large group of subjects with widely ranging renal function. During the last two years, we administered a simultaneous injection of 74 MBq of MAG3 and 0.74 MBq of OIH to each subject who underwent a renal scintigraphic study in our hospital. They were 53 females and 50 males (mean age: 52 years; range: 18-70 years), either normal (30) or with a diagnosis of essential hypertension (53), chronic renal failure (14), renal calculi (5), or renal transplant (1). Plasma clearance and ERPF were calculated with both radiocompounds by using the exponential formula of Tauxe and coworkers and a single plasma concentration determination sampled 44 min after injection of the two tracers. The time-activity curves for kidney and blood were of the same bi-exponential type. The mean ratio between the two plasma clearances was 0.49. The linear regression of the ERPF values obtained with the two radiocompounds was highly significant (r = 0.69; p less than 0.0001) and is expressed by the equation: ERPF (MAG3) = 0.453 ERPF (OIH) + 25.7. These data suggest that the routine calculation of ERPF from MAG3 clearance is consistent with the results obtained from OIH clearance. In conclusion, MAG3 appears to be a good predictor of ERPF in routine clinical practice.     

Comparative study of the kinetics of the renal tracers 99Tcm-MAG3 and 131I-hippuran.

Serial measurements of plasma activity, plasma protein binding and urine excretion were obtained in order to study 99Tcm-MAG3 (MAG) and 131I-Hippuran (OIH) kinetics after simultaneous injection of both tracers in 21 patients with various renal diseases. Results were compared on the basis of a compartmental model, calculating the rate constants as well as the clearance and volume of distribution. Protein binding was calculated in 10 patients (mean: MAG = 54.7%, OIH = 33.8%). The dependence of time, tracer and patient factors was shown by ANOVA. Time was independent, with tracer and patient factors and their interaction being significant. The mean value of the renal excretion constant was equal for the two tracers (k12 = 0.052 min-1). The clearance values were found to be highly correlated (r = 0.982) with a ratio of 0.57 between them. The volumes of distribution in litres were 4.1 (MAG) and 7.0 (OIH). One-hour urine excretion was nearly the same for both tracers (MAG: 64%, OIH: 63% of the injected dose).     

Mechanism of renal concentration of technetium-99m glucoheptonate

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.     

Evaluation of Tc-99m mercaptoacetyltriglycine in patients with impaired renal function

Technetium-99m mercaptoacetyltriglycine (MAG3), a new radiopharmaceutical shown to have biological properties similar to iodine-131 o-iodohippurate (OIH) in animals and healthy volunteers, was compared with OIH in 15 patients with varying degrees of renal impairment. The Tc-99m MAG3 images were uniformly superior, regardless of the serum creatinine level. There was no significant difference in the 30-minute blood clearance of OIH and MAG3. MAG3 protein binding (78.6%) was greater than that of OIH (53.1%) (P less than or equal to .01), and the volume of distribution of MAG3 (7.06 liters) was less than that of OIH (10.78 liters) (P less than or equal to .01). In six patients the 30-minute urinary excretion of the two agents was essentially identical. The time to the peak height of the renogram curves was more rapid for MAG3 than for OIH using both cortical and whole-kidney regions of interest (P less than or equal to .02). In summary, preliminary results suggest that Tc-99m MAG3 performs well in patients with impaired renal function and may well be an acceptable replacement for OIH. A kit formulation is currently undergoing clinical evaluation.     

Reproducibility of single-sample clearance of 99mTc-mercaptoacetyltriglycine and 131I-orthoiodohippurate.

Recent literature has questioned whether 99mTc-mercaptoacetyltriglycine (MAG3) clearance measurements are reproducible enough for routine clinical monitoring of renal function. For many years, we have routinely followed the renal function of patients with spinal cord injuries using a combination of radionuclide imaging and clearance measurement. METHODS: In this study, we retrospectively review 1626 effective renal plasma flow (ERPF) measurements in 197 patients with paraplegia or quadriplegia performed over a 21-y period, using 131I-orthoiodohippurate (OIH) through 1990 and MAG3 since 1991. MAG3 clearance was divided by 0.53 to convert it to ERPF. Reproducibility was measured as pooled SD from the single-patient linear regression lines of ERPF versus time. RESULTS AND CONCLUSION: There was no significant difference between MAG3 (SD = 46 mL/min, n = 907) and OIH (SD = 52 mL/min, n = 719). The data were therefore combined to obtain the SD for a single ERPF measurement, which was 49 mL/min. The corresponding coefficient of variation was 8.5% of the mean value of 581 mL/min. In our experience, this is adequate for monitoring the renal function of these patients.