Transplant renography: 99m-Tc-DTPA versus 99m-Tc-MAG3. A preliminary note

99mTc-MAG3 has been proposed as a replacement for both 131I-hippuran and 99mTc-DTPA on clinical grounds. We undertook a prospective preliminary study to ascertain whether 99mTc-MAG3 works better than 99mTc-DTPA in the follow up of renal transplant recipients. Seventeen patients (21 renograms each MAG3 and DTPA) were studied, together, with a reference group of 10 patients in whom MAG3 and Hippuran clearance rates were determined simultaneously. As expected, 99mTc-MAG3 analog images were excellent and 99mTcMAG3 clearance correlated very well with 131I-hippuran clearance (r = 0.978). MAG3 values were 60% of hippuran values. However, when the corresponding renographic and perfusion findings were faced with different diagnostic challenges, such as post transplant renal failure and rejection, 99mTc MAG3 did not differ from 99mTc-DTPA in a significant way. 99mTc-DTPA was superior to 99mtc-MAG3 in one case of rejection.     

Technetium-99m DTPA dimethyl ester: a renal function imaging agent. Comparative studies in animals with technetium-99m mercaptoacetyl triglycine and 131I-ortho-iodohippurate

The dimethyl ester of diethylene triamine penta-acetic acid (DMDTPA) (I) can be easily and efficiently labelled with 99mTc. This method can be readily adapted for kit formulations to produce a highly stable and very pure chelate, as shown by paper electrophoresis and reverse-phase high performance liquid chromatography experiments. In mice, this chelate was excreted unchanged in the urine, and the amount of renal excretion was much higher than that of 99mTc-DTPA and comparable with that of 99mTc-mercaptoacetyl triglycine (99mTc-MAG(3)) at two different time points. The renal excretion of co-injected 131I-ortho-iodohippurate (131I-OIH), however, was significantly greater than that of the 99mTc chelates. The renal clearance values of 99mTc-DMDTPA and 99mTc-MAG(3) were also similar and exceeded the corresponding value for 99mTc-DTPA, but were only half that of the 131I-OIH value in the rat. The renograms for 99mTc-DMDTPA and 99mTc-MAG(3) showed overall similarity in a dog model. The diethyl ester (III) and monoethyl ester (II) of DTPA, after labelling with 99mTc, produced the same chelate, as shown by analytical results and biological data, indicating that one of the ester groups in the DTPA diester is dealkylated during the chelation procedure. To confirm this, two more ligands, diethylene triamine 1,4,7,7-tetra-acetic acid (IV) and diethylene triamine 1,4,7-triacetic acid (V), were synthesized, resembling DTPA monoalkyl ester (II) and dialkyl ester (I, III), respectively, in the arrangement of the donor atoms. Ligand IV but not ligand V, on 99mTc chelation, can generate the specific pharmacophore for renal tubular transport that is also present in the ester chelates 99mTc-I, 99mTc-II and 99mTc-III, as shown by their decreased renal excretion in mice pretreated with a renal tubular transport inhibitor such as probenecid.     

Pharmacokinetics of technetium-99m-MAG3 in humans

Technetium-99m-mercaptoacetylglycylglycylglycine (99mTc-MAG3) is introduced to replace o-iodohippurate (OIH) for renal function studies. For interpretation of clinical findings, extensive pharmacokinetic studies were performed on patients. These showed that 99mTc-MAG3, compared with OIH, has a higher plasma-protein binding, an essentially higher intravascular concentration, a smaller volume of distribution and, with practically identical biologic half-lives, a correspondingly lower clearance. Simultaneous steady-state measurements resulted in a 1.5-fold higher clearance of OIH than of 99mTc-MAG3 (n = 124). Competitive inhibition of the tubular transport system by p-aminohippurate (PAH) (20 patients) revealed a distinctly higher suppression of the 99mTc-MAG3 clearance than of OIH which indicates a lower affinity of the 99mTc complex to the tubular cell. The plasma extraction efficiencies of both agents, measured during surgery (n = 5), did not indicate an extrarenal elimination of 99mTc-MAG3. This new radiopharmaceutical is a pragmatic alternative to OIH and offers advantages not only for scintigraphic imaging but is also suited for quantitative renal function studies.     

Clinical experience with 99mTc-MAG3, mercaptoacetyltriglycine, and a comparison with 99mTc-DTPA

The preparation, application and clinical usage of 99mTc-mercaptoacetyltriglycine, MAG3, a tubular secreted compound, is described in the first 225 patients in a phase III study. Image quality, relative renal function, and renal transit times were compared with a 4 fold greater administered activity of 99mTc-DTPA in 11 patients. Correlation coefficients of 0.94 for relative function, 0.83 for parenchymal transit time index and 0.82 for whole kidney transit time index were found. Frusemide responses were similar. 99mTc-MAG3 is an efficacious radiopharmaceutical for routine renal radionuclide studies, giving excellent image quality in patients with hypertension, poor renal function, obstructive nephropathy or a renal transplant.     

Evaluation of the renal excretion characteristics of technetium-99m mercaptoacetylglycyl-D-alanylglycine in healthy volunteers.

During a study of C-methyl derivatives of technetium-99m mercaptoacetyltriglycine (99mTc-MAG3) it was found that the isomer of 99mTc-mercaptoacetylglycyl-D-alanylglycine (99m-TC-MAGAG-DA) is superior to 99mTc-MAG3 with regard to its renal excretion characteristics in both mice and the baboon. We have now compared the renal handling of 99mTc-MAGAG-DA and 99mTc-MAG3 in 6 healthy volunteers in a paired study. Renograms of 99mTc-MAGAG-DA show a shorter time to renal maximum and a lower residual renal activity at 30 min post-injection (p.i.). The urinary excretion of 99mTc-MAGAG-DA is higher at both 30 and 60 min p.i. The plasma concentration of 99mTc-MAGAG-DA is lower than that of 99mTc-MAG3 at each moment up to 60 min p.i., and the plasma clearance is accordingly higher. It is concluded that 99mTc-MAGAG-DA is excreted more efficiently than 99mTc-MAG3, but the preparation of 99mTc-MAGAG-DA requires a HPLC purification step, and this limits its practical clinical usefulness.     

Radiation dosimetry for technetium-99m-MAG3, technetium-99m-DTPA, and iodine-131-OIH based on human biodistribution studies.

Radiation dose estimates were calculated for the renal agents 99mTc-DTPA, 99mTc-MAG3, and 131I-OIH from biodistribution data gathered in groups of healthy human volunteers. Biokinetics were evaluated by Anger camera imaging, blood sampling, and urine collection and counting. Collected data were fit to four- or five-compartmental models using the CONversational Simulation, Analysis, and Modeling (CONSAM) software. Radiation dose estimates were performed using standard MIRD techniques. Average residence times in urinary bladder, kidney, and remainder of the body were used to predict radiation dose equivalents and effective dose equivalents for the three agents. Doses for DTPA and MAG3 were very similar and much lower on a per unit injected activity than OIH. The effective dose equivalents were 3.3 mSv/370 MBq for 99Tc-DTPA, 3.7 mSv/370 MBq for 99mTc-MAG3, and 0.99 mSv/11.1 MBq for 131I-OIH for bladder voiding every 4.8 hr; effective dose equivalents were 2.0 mSv/370 MBq for 99mTc-DTPA, 1.5 mSv/370 MBq for 99mTc-MAG3, and 0.28 mSv/11.1 MBq for 131I-OIH for bladder voiding at 30 min and then every 4.0 hr. Patients should void at the conclusion of the study, as early voiding can reduce the gonadal radiation dose by a factor of 2 to 3.     

Reproducibility of technetium-99m mercaptoacetyltriglycine clearance in patients with impaired renal function

BACKGROUND: The aim of this study was to determine the reproducibility of technetium-99m mercaptoacetyltriglycine (99mTc-MAG3) clearance in patients with a 99mTc-MAG3 clearance below 100 ml/min/1.73 m2. METHODS: Two separate multi-sample clearance studies were performed in 16 patients at a 1 week interval. The clearances were calculated according to the open two-compartment model of Sapirstein et al., accepting the 90, 120 and 180 min samples as the last points of the biexponential curve. The clearance measurements were also performed according to the single-sample methods of Russell et al. and Bubeck using the fitted value at 44 min. RESULTS: There was no significant difference between the two clearance measurements for all five samples (P>0.05). There was a systematic increase in clearance measurements of 8.0+/-2.7% from the 180 to 120 min samples and 4.8+/-2.0% from the 120 to 90 min samples. Both single-sample methods (Bubeck and Russell et al.) gave more divergent results than multi-sample methods. The mean and standard deviation (%) of the normalized differences between two successive tests were -3.9+/-12.6, -2.4+/-13.1, -1.9+/-14.9, -4.1+/-53.5 and -13+/-82.1 for 90, 120 and 180 min samples and the Russell et al. and Bubeck methods, respectively. CONCLUSION: Single-sample methods give very poor reproducibility and accuracy and should not be used in patients with poor renal function. The reproducibility of 99mTc-MAG3 clearance using the multi-sample method (90 min) in patients with impaired renal function is 12.6%, which is similar to that in patients with good renal function and that obtained with other tubular agents. Whether this level of reproducibility is satisfactory for documenting serial changes in an individual patient with a 99mTc-MAG3 clearance below 100 ml/min/1.73 m2 depends on the expectation of the clinician.     

Prospective validation of a single sample technique to determine technetium-99m-MAG3 clearance.

Technetium-99m-MAG3 clearance is proportional to OIH clearance and can be used directly as a measure of renal function. Multiple plasma sample, two-compartment clearance data from three studies were recently pooled to develop a single-sample regression equation for determining the clearance of 99mTc-MAG3. To test this published equation, a prospective study was conducted in 34 patients with a wide range of renal function. Multiple plasma samples were obtained from 9 to 60 min following the bolus injection of 99mTc-MAG3 and the clearances were calculated based on a single injection, two-compartment model. Clearances were also calculated using a single 43-min plasma sample and the published regression equation. There was an excellent correlation (r = 0.976) between the two clearances; the slope of the regression line was 1.01 with an intercept of -26.6; the standard error of the estimate was 24 ml/min. In conclusion, the current regression equation provides a good estimate of 99mTc-MAG3 clearance.     

Poor technetium-99m-DMSA renal uptake with near normal technetium-99m-DTPA uptake caused by tubulointerstitial renal disease.

We present a patient with tubulointerstitial renal disease and poor renal 99mTc-DMSA uptake. A 99mTc-DTPA scan was normal and the creatinine clearance only minimally decreased. In this case, 99mTc-DMSA uptake did not correlate with "global renal function," but rather with the functioning tubular mass.     

99mTc-MAG3: dynamic studies in patients with renal disease

Animal studies have suggested that 99mTc-mercapto-acetylglycyl-glycyl-glycine (99mTc-MAG3) might be suitable for the determination of the renal plasma flow (RPF) because of its high renal clearance. In this study 131I-orthoiodohippurate (131I-OIH) and 99mTc-MAG3 (labeling always greater than 95%) were administered simultaneously in 11 patients (creatinine clearance ranging from 14 to 130 ml/min per 1.73 m2) to measure effective RPF(ERPF) using the standard technique (UV/P). Glomerular filtration rate (GFR; clearance of 125I-thalamate, 125I-OT) was also measured. The mean ratio of 99mTc-MAG3 clearance to 131I-IOH clearance was 0.55 +/- 0.02 (SEM), P less than 0.01, n = 16, and was independent of GFR and ERPF. To study this difference in renal handling of the radiopharmaceuticals, renal extractions by the right kidney were determined in another six patients after a single shot of the agents. Renal extraction of 99mTc-MAG3 was 0.60 +/- 0.03 after 5 min, and 0.41 +/- 0.08 after 30 min. Renal extraction of 131I-OIH amounted to 0.86 +/- 0.04 and 0.77 +/- 0.03, respectively. Using renal extractions of 0.41 and 0.77, respectively, it appeared that calculated renal plasma flows measured simultaneously with 99mTc-MAG3 and 131I-OIH were similar. Protein binding 30 min after the priming dose was 66% for 99mTc-MAG3 and 47% for 123I-OIH. We conclude that in spite of a high renal clearance (ratio to 125I-OT clearance 2.69 +/- 0.27), 99mTc-MAG3 seems unsuitable for an accurate determination of the RPF.(ABSTRACT TRUNCATED AT 250 WORDS)     

Synthesis and renal excretion of technetium-99m-labeled organic cations.

Organic cations are excreted more efficiently than organic anions in uremia suggesting superiority as renal imaging agents. In this study, three 99mTc-labeled cationic cyclam complexes were synthesized and their renal clearance quantified in rats. The complexes are cleared at a rate of about 2.5-3 times that of inulin and about 60% that of p-amino-hipurate. Inhibition of 99Tc-cyclam excretion by quinine indicates transport by the organic cation process. Comparative in vivo imaging experiments demonstrated that in normal rats 99mTc-cyclam reached peak renal activity 1.8 +/- 0.6 min after injection, a value intermediate between that for [131I]OIH (1.0 +/- 0) and 99mTc-MAG3 (2.8 +/- 0.6). In rats injected with the acute nephrotoxin cisplatin, the times to peak were lengthened with the relative order being 99mTc-cyclam > 99mTc-MAG3 > [131I]OIH. The results demonstrate that cationic complexes may be useful for renal imaging diagnostic applications.     

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.     

Uterine technetium-99m mercaptoacetyltriglycine and diethylene triamine penta-acetic acid uptake in the scintigraphic evaluation of transplanted kidneys.

An anuric 35-year-old woman with a renal transplant underwent serial renal scintigraphy studies to screen the kidney function. A hypervascular pelvic mass in the region of the bladder was identified during technetium-99m mercaptoacetyltriglycine (MAG3) and also during 99mTc diethylene triamine penta-acetic acid (DT-PA) scintigraphy. She was in the secretory phase of the uterine cycle during the study and had no gynaecological problem to explain the radioactivity accumulation. The accumulation of 99mTc-MAG3 mimicking the bladder was considered as uterine activity. To our knowledge, this is the first case of uterine visualization with 99mTc-MAG3.     

99mTc-DTPA renal studies for acute tubular necrosis: specificity of dissociation between perfusion and clearance

In order to evaluate the usefulness of radionuclide renal studies in differentiating acute tubular necrosis from other causes of decreased renal clearance (e.g., rejection) in renal transplant patients, we assumed that acute tubular necrosis would be common during the first 4 days after cadaveric transplantation (group 1) and uncommon 3 weeks or longer after transplantation (group 2). There were 38 renal studies in 34 patients in group 1 and 62 studies in 27 patients in group 2. Each renal study consisted of both a technetium-99m-DTPA and an iodine-131-hippuran study. Perfusion, clearance, and transit time in the 99mTc-DTPA study, and clearance and transit time in the 131I-hippuran study were visually graded on a 5 point scale without knowledge of the time of study or clinical diagnosis. There were 19 studies in group 1 and 25 studies in group 2 with clearance decreased two or more gradations. Eleven 99mTc-DTPA studies had perfusion 2 or more gradations better than clearance; all 11 were in group 1 (p less than 0.01). Other dissociations within the 99mTc-DTPA and 131I-hippuran studies, or between them, did not distinguish the two groups. Data support the hypothesis that decreased clearance with relatively well preserved perfusion in 99mTc-DTPA studies is common in acute tubular necrosis and uncommon in other causes of decreased renal clearance.     

Estimation of technetium-99m-MAG3 renal clearance in children: two gamma camera techniques compared with multiple plasma samples.

Dynamic renal scintigraphy using technetium-99m mercaptoacetylglycylglycylglycine (MAG3) has been described in adults, and clearance values have been established using multiple plasma samples. This study of renal clearance has compared two fundamentally different gamma camera techniques (both of which require a single blood sample) with the multiple blood sampling technique in children (n = 30). Results show that a 40-min dynamic 99mTc-MAG3 renal scintigram coupled with a single plasma sample will allow analysis of the data so that clearance values, which are similar to those from multiple plasma samples, may be calculated. The curve generated from the cardiac region of interest (ROI) provided clearances values that had a high correlation coefficient (0.939-0.951) compared to the multiple-plasma sample technique immaterial of the timing of the blood sample. The renal uptake method of clearance had a lower correlation coefficient (0.89-0.92), which varied with the timing of the blood sample compared to the multiple-plasma sampling technique. This study has demonstrated that an extended gamma camera acquisition coupled with a single-plasma sample may be used for quantitative renal function studies using 99mTc-MAG3.     

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.     

Evaluation of 99mTc-mercaptoacetyltriglycine-biocytin as a new hepatobiliary imaging agent in mice coinjected with bilirubin

We evaluated 99mTc-labeled mercaptoacetyltriglycine (99mTc-MAG3)-biocytin as a hepatobiliary imaging agent in the absence and presence of bilirubin in mice. We then compared its pharmacokinetic parameters; peak liver/heart activity ratio (rmax) and half clearance time (HCT) with those of 99mTc-labeled diisopropyl-iminodiacetic acid (99mTc-disofenin). Balb/c mice were injected intravenously with hepatobiliary agent (99mTc-MAG3-biocytin or 99mTc-disofenin) alone or in combination with bilirubin at two doses (7 and 14 mg/kg) dissolved in 5% human serum albumin. Images were acquired every 15 s for 30 min with a gamma-camera equipped with a pinhole collimator. Dynamic images showed rapid hepatic uptake of 99mTc-MAG3-biocytin, with rapid clearance from the blood and rapid excretion via the biliary system. Its hepatic uptake was not affected by bilirubin coinjection, whereas 99mTc-disofenin coinjected with bilirubin showed a higher blood background than 99mTc-disofenin alone. These qualitative findings were reflected in pharmacokinetic parameters, rmax and HCT. The rmax was obtained from plots of time versus liver/heart activity ratios obtained in equal-area regions of interest over the heart and liver. The HCT was calculated from the hepatic clearance curve from plots of time versus liver activity. 99mTc-MAG3-biocytin without bilirubin coinjection showed an rmax of 8.9+/-1.3 and an HCT of 399+/-36 s. These values did not change even when 14 mg/kg of bilirubin were coinjected. By contrast, the parameters for 99mTc-disofenin with bilirubin were significantly (p < 0.01) affected by 14 mg/kg of bilirubin coinjection: rmax was decreased from 7.9+/-2.5 to 1.4+/-0.2 and HCT was increased from 292+/-32 s to 782+/-133 s. 99mTc-MAG3-biocytin hepatobiliary scintigraphy in mice is not affected by bilirubin coinjection, and this hepatobiliary agent appears to offer promise for estimating hepatic function in patients with high bilirubin levels.     

Increased perinephric activity in 99mTc-DTPA studies of renal transplants.

All 99mTc-DTPA studies of renal transplant patients whose grafts infarcted during a three-and-one-half-year period were reviewed. Four patients demonstrated absent renal perfusion and clearance and absent bladder activity. Three of these exhibited increased perinephric 99mTc-DTPA activity and never regained renal function. The fourth patient did not demonstrate increased perinephric activity, and some return of graft function appeared in a subsequent 99mTc-DTPA study. The pathogenesis of increased perinephric activity is unknown, but may signify renal infarction, and its absence may indicate potential renal viability.     

Pharmacokinetic characteristics of 99mTc-Ethylene-l-dicysteine (99mTc-EC)

BACKGROUND: Ethylenedicysteine-99mTc (99mTc-EC) has been more and more commonly applied in dynamic studies as well as for clearance determinations. However, it was necessary to investigate in detail the pharmacokinetic characteristics of the radiopharmaceutical which may be important for its applicability in assessment of renal function. RESULTS: Kidney images obtained from renoscintigraphy are characterised by excellent quality without visualisation of the organs adjacent to kidneys (liver, spleen). Renoscintigraphic curves demonstrate typical shapes with TMAX and T1/2 values not differing from the corresponding values obtained for other radiopharmaceuticals (99mTc-MAG3, 131I-OIH). In plasma, 99mTc-EC binds with proteins to a considerably lesser degree (c. 1/3) than 131I-OIH (c. 2/3), or 99mTc-MAG3 (> 9/10). No binding of 99mTc-EC with erythrocytes has been demonstrated, whereas 131I-OIH attaches to or penetrates the red blood cells (10-12%). 99mTc-EC is quickly excreted from the organism: 40 min after i.v. injection up to 70% of the administered radiopharmaceutical is found in urine, and at 1 and 1.5 h after the administration 80% and 95%, respectively. The distribution of 99mTc-EC in the organism can be described in a fully satisfactory way by means of an open two-compartment model, which allows this model to be used for clearance determinations. Comparison of the values of renal plasma clearance without collection of urine with the values determined by means of measurement of activity excreted with urine and mean blood concentration over a finite time interval leads to the conclusion that extrarenal plasma clearance of this compound (via the liver?) is negligible and amounts to c. 17 ml/min (5-6% of the total). The obtained correlation between clearance values for 99mTc-EC and 131I-OIH supports the contention that extrarenal excretion rate of 99mTc-EC (through the liver and bile ducts) is lower than the corresponding rates of either 131I-OIH or 99mTc-MAG3. A very close correlation between clearance values for 99mTc-EC and ERPF (131I-OIH clearance) and between their extraction constants (r = 0.91 and 0.92, respectively), allows for the introduction of 99mTc-EC to the assessment of renal function instead of 131I-OIH. Effective dose to the patient from unit activity of 99mTc-EC is comparable with that resulting from administration of other radiopharmaceuticals labelled with 99mTc.     

Evaluation of renal function from 99mTc-MAG3 renography without blood sampling.

To develop a camera-based method for evaluating renal function with 99mTc-mercaptoacetyltriglycine (MAG3), we examined the relationship between various renogram parameters and 99mTc-MAG3 clearance. METHODS: Twenty-one patients underwent renal scintigraphy with 99mTc-MAG3. Eighty 3-s frames were obtained after the bolus injection of 250 MBq tracer, followed by the collection of 52 30-s frames. Regions of interest were drawn for the kidneys, perirenal background areas and subrenal background areas, and background-subtracted renograms were generated. Renal accumulation at 0.5-1.5, 0.5-2, 1-2, 1-2.5 and 1.5-2.5 min after tracer arrival in the kidney was calculated as area under the background-subtracted renogram, and percent renal uptake was obtained after correction for soft-tissue attenuation and injected dose. The slope of the renogram was determined for the same segments used in calculating area under the renogram, and slope index was computed as slope corrected for attenuation and injected dose. Percent renal uptakes and slope indices were correlated by linear regression analysis with 99mTc-MAG3 clearance measured using a single blood sampling method. RESULTS: Among the values of percent renal uptake, the value obtained at 1.5-2.5 min using the perirenal background correlated best with 99mTc-MAG3 clearance. The slope index at 0.5-1.5 or 0.5-2 min using the subrenal background provided better accuracy than percent renal uptake for predicting clearance. There were no substantial differences in the relative function of the right kidney between the methods using percent renal uptake and slope index. CONCLUSION: 99mTc-MAG3 clearance can be assessed with acceptable accuracy by a camera-based method. The method based on the slope of the renogram may replace the one based on the area under the renogram in evaluating renal function from 99mTc-MAG3 renograms.