Prospective validation of single plasma sample 99mTc-ethylenedicysteine clearance in adults.

99mTc-L,L-ethylene, L, dicysteine (EC) clearance shows strong correlation with orthoiodohippurate clearance, and it is possible to estimate effective renal plasma flow from 99mTc-EC clearance. In routine clinical studies, it is practical to use the one or two plasma sample method instead of multiple plasma samples for clearance determination. A single-sample technique was developed for 99mTc-EC, and a regression formula was generated. A prospective study tested the validity of this regression formula. METHODS: The study population was composed of 26 patients with a wide range of renal function. Multiple plasma sample 99mTc-EC clearances were calculated from all patients using the open two-compartment model. Single plasma sample clearances were also determined from the 54-min plasma sample using the regression formula published previously. RESULTS: The multiple-sample plasma clearance of 99mTc-EC ranged from 46 to 668 mL/min with a mean of 300.76 +/- 150.73 mL/min. The clearances obtained from the 54-min plasma sample ranged from 49 to 699 mL/min, with a mean of 297.39 +/- 152.23 mL/min. There was an excellent correlation between the clearances obtained by the two techniques (r = 0.99, slope = 0.9911). The standard error of estimation was found to be 25.9 mL/min. CONCLUSION: This study suggests that 99mTc-EC clearance can be estimated from 54-min plasma samples with an acceptable error of estimation for most routine clinical studies.     

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.     

How gender and age affect iodine-131-OIH and technetium-99m-MAG3 clearance

OBJECTIVE: The relationship between age and effective renal plasma flow (ERPF) results, as measured in nuclear medicine, is well known. This paper explores the relationships among gender, age, and ERPF measurements. After reading this paper, the nuclear medicine technologist should be able to: (a) discuss the importance of establishing normal range values for ERPF that include age and gender variables; (b) state how age affects ERPF results; and (c) state how gender affects ERPF results.     

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.     

Use of technetium-99m-MAG3 for renal scintigraphy after angiotensin-converting enzyme inhibition.

Technetium-99m-mercaptoacetyltriglycine (99mTc-MAG3) was tested in 82 hypertensive patients submitted to renal scintigraphy 1 hr after oral premedication with 50 mg of Captopril. Baseline studies were obtained only for those patients showing abnormal findings in the provocative study. All patients underwent renal arteriography. Sensitivity and specificity for the detection of renal artery stenosis (RAS) greater than 50% were 89% and 91%, respectively. After Captopril administration, tracer parenchymal transit time increased significantly in ischemic kidneys (334 +/- 93 sec in baseline conditions versus 468 +/- 96 sec after Captopril, p less than 0.001) but not in kidneys with no RAS or RAS less than 50% (243 +/- 46 sec versus 271 +/- 95 sec, p = ns). False-positive responses were mostly bilateral and associated with a marked decrease in blood pressure. Technetium-99m-MAG3 is an effective compound for detecting RAS greater than or equal to 50% with Captopril renal scintigraphy. Performing the provocative test as a first step considerably reduced the number of scintigraphic studies required.     

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.     

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.     

Technetium-99m-MAG3 versus iodine-123-OIH: renal clearance and distribution volume as measured by a constant infusion technique.

The renal clearance and distribution volume of 99Tc-mercaptoacetyltriglycine (MAG3) and 123I-o-iodohippurate (OIH) were determined separately in six normal male volunteers using the constant infusion clearance technique in order to validate single injection clearance techniques and subsequently the normal values for these parameters. MAG3 renal clearance was 257 +/- 24 ml/min/1.73 m2, compared to the OIH clearance of 556 +/- 46 ml/min/1.73 m2 resulting in a MAG3/OIH clearance ratio of 0.47 +/- 0.06. The MAG3 and OIH apparent distribution volumes at steady-state were 14.8 +/- 3.7 and 19.4 +/- 5.3 liters, respectively, the latter value approximating the extra cellular fluid volume. Urinary excretion in the 0-30-min period after intravenous administration was 64.4 and 70.2% for MAG3 and OIH, respectively. This investigation revealed some significant differences in the normal values of the renal clearance and distribution volume of MAG3 compared with other studies.     

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.     

Reproducibility of technetium-99m ethylenedicysteine clearance.

It has been shown that technetium-99m ethylenedicysteine ((99m)Tc-EC) clearance displays a strong correlation with orthoiodohippurate clearance and that it is possible to estimate effective renal plasma flow from (99m)Tc-EC clearance. However, in routine practice, when monitoring renal function of patients by clearance determinations it is imperative to test the reproducibility of the clearance technique in order to decide whether the changes in renal function are related to disease or not. The aim of this study was to test the reproducibility of (99m)Tc-EC clearance. The study group comprised 13 patients aged between 24 and 58 years (eight female and five male). Two patients had single kidneys due to agenesis and hypoplasia. Plasma creatinine and BUN levels were within the normal range and remained stable between two clearance studies. None of the patients were receiving medication. Two separate multiple sample clearance studies were performed in each patient within a week. The difference between two studies was expressed as a percentage of the mean value of the two studies, and the standard deviation of these percentages represented the precision. The plasma clearance of (99m)Tc-EC in the first-step studies ranged from 190 ml/min to 561 ml/min with a mean of 411+/-101 ml/min. The clearances obtained from the second-step studies ranged from 248 ml/min to 552 ml/min, with a mean of 387+/-94 ml/min. There was no statistically significant difference between the two clearance studies (P>0.05). There was a mean difference of 5.3% between the first and second clearance studies, and the precision was found to be 12.7%. In conclusion, this study suggested that consecutive (99m)Tc-EC clearance measurements should be interpreted cautiously.     

Determination of the technetium-99m mercaptoacetyltriglycine plasma clearance in children by means of a single blood sample: a multicentre study

A multicentre European study was undertaken in order to determine a reasonable algorithm allowing the determination of overall technetium-99m mercaptoacetyltriglycine clearance using a single blood sample. Employing multiple blood sample clearance as a reference method, it was shown that an acceptable estimation of the MAG3 renal clearance could be obtained using a blood sample taken at any time between 30 and 40 min after tracer injection. After correction for body surface area, comparison of clearance determined using (a) the single blood sample and (b) the multiple blood samples provided a coefficient of correlation of 0.949 and an SEE of 27 ml/min. This algorithm is valid for clearance values higher than 100 ml/min/1.73 m² and for children older than 1 year of age.     

Reproducibility of technetium-99m ethylenedicysteine clearance

It has been shown that technetium-99m ethylenedicysteine (^99mTc-EC) clearance displays a strong correlation with orthoiodohippurate clearance and that it is possible to estimate effective renal plasma flow from ^99mTc-EC clearance. However, in routine practice, when monitoring renal function of patients by clearance determinations it is imperative to test the reproducibility of the clearance technique in order to decide whether the changes in renal function are related to disease or not. The aim of this study was to test the reproducibility of ^99mTc-EC clearance. The study group comprised 13 patients aged between 24 and 58 years (eight female and five male). Two patients had single kidneys due to agenesis and hypoplasia. Plasma creatinine and BUN levels were within the normal range and remained stable between two clearance studies. None of the patients were receiving medication. Two separate multiple sample clearance studies were performed in each patient within a week. The difference between two studies was expressed as a percentage of the mean value of the two studies, and the standard deviation of these percentages represented the precision. The plasma clearance of ^99mTc-EC in the first-step studies ranged from 190 ml/min to 561 ml/min with a mean of 411±101 ml/min. The clearances obtained from the second-step studies ranged from 248 ml/min to 552 ml/min, with a mean of 387±94 ml/min. There was no statistically significant difference between the two clearance studies (P>0.05). There was a mean difference of 5.3% between the first and second clearance studies, and the precision was found to be 12.7%. In conclusion, this study suggested that consecutive ^99mTc-EC clearance measurements should be interpreted cautiously. Received 31 January and in revised form 1999     

Reproducibility of technetium-99m mercaptoacetyltriglycine clearance

The aim of this paper was to determine the reproducibility (precision) of technetium-99m mercaptoacetyltriglycine (MAG3) clearance and to compare it with that of chromium-51 ethylenediamine tetra-acetic acid (EDTA). Twelve young volunteers (aged between 21 and 34 years), without any history of medical problems, were enrolled in this study. The test was performed twice, at an interval of 8 days and under similar physiological conditions. After the intravenous injection of both tracers, 15 blood samples were taken between 3 and 240 min. A biexponential fit was adapted to the plasma disappearance curves (5- to 120-min samples for^99mTc-MAG3 and 10- to 240-min samples for⁵¹Cr-EDTA); the clearances were calculated according to Sapirstein and corrected for body surface area. The mean clearance values were 110 (range 85–130) and 226 (range 109–319) ml/min/1.73 m², respectively, for⁵¹Cr-EDTA and^99mTc-MAG3. For⁵¹Cr-EDTA clearance, the mean difference between the first and the second measurement was –2.1% of the mean of the two successive values (SD: 8.4%). In ten cases, the difference was less than 12%; in two cases, the differences were 15% and 18%, respectively. For^99mTc-MAG3 clearance, the mean difference between the first and the second measurement was –20% of the mean of the two successive values (SD: 25%). In six cases, the difference was less than 12%; in four cases, between 15% and 40%; and in two cases, more than 60%. Methodological factors (impurites contained in the commercial kit, variable protein binding) as well as physiological factors (pH of urine, sodium load, stress) may explain the lack of precision of the^99mTc-MAG3 clearance. It is concluded that changes in^99mTc-MAG3 plasma clearance should be interpreted with care in daily routine.     

Stimulated salivary clearance of technetium-99m pertechnetate

A method to determine stimulated salivary clearance of pertechnetate is presented. It is easy to perform and separates normal patients (range 15.0 to 40.3 ml/min) from patients with known salivary disorders (range 1.2 to 10.6 ml/min).     

Technetium-99m-MAG3 clearance as a parameter of effective renal plasma flow in patients with proteinuria and lowered serum albumin levels.

Although the renal clearance of 99mTc-MAG3 is about 60% of the 131I-hippurate clearance, 99mTc-MAG3 clearance may be useful to estimate ERPF. In one study, however, proteinuria seemed to influence the MAG3/hippurate clearance ratio. In order to establish whether proteinuria or serum albumin level has influence on this ratio, a comparison was made between 99mTc-MAG3 clearance and 131I-hippurate clearance in 14 patients. There was a good linear correlation between MAG3 and hippurate clearance, although the standard error of estimate of ERPF from MAG3 was relatively large, which remained unexplained. No correlation was found between proteinuria and MAG3/hippurate clearance ratio nor between serum albumin level, GFR, FF, ERPF and the MAG3/hippurate clearance ratio. We therefore conclude that there is no correlation between proteinuria and albumin level and the MAG3/hippurate ratio. A reasonable estimation of ERPF with MAG3 can be made in patients with proteinuria and lowered serum albumin levels although the estimation may be less accurate.     

Estimation of technetium 99m mercaptoacetyltriglycine plasma clearance by use of one single plasma sample.

Recent studies have shown that technetium 99m mercaptoacetyltriglycine (MAG-3) is a suitable replacement for iodine 131 or 123 hippurate in gamma-camera renography. Also, the determination of its clearance is of value, since it correlates well with that of hippurate and thus may be an indirect measure of renal plasma flow. In order to simplify the clearance method we developed formulas for the estimation of plasma clearance of MAG-3 based on a single plasma sample and compared them with the multiple sample method based on 7 plasma samples. The correlation to effective renal plasma flow (ERPF) (according to Tauxe's method, using iodine 123 hippurate), which ranged from 75 to 654 ml/min per 1.73 m2, was determined in these patients. Using the developed regression equations the error of estimate for the simplified clearance method was acceptably low (18-14 ml/min), when the single plasma sample was taken 44-64 min post-injection. Formulas for different sampling times at 44, 48, 52, 56, 60 and 64 min are given, and we recommend 60 min as optimal, with an error of estimate of 15.5 ml/min. The correlation between the MAG-3 clearances and ERPF was high (r = 0.90). Since normal values for MAG-3 clearance are not yet available, transformation to estimated ERPF values by the regression equation (ERPF = 1.86 x CMAG-3 + 4.6) could be of clinical value in order to compare it with the normal values for ERPF given in the literature.