Abstract
Renal function measurements using 99mTc-DTPA and 99mTc-MAG3 dynamic scintigraphs were compared to those obtained using 99mTc-DMSA static scintigraphy. Eighteen experimental rabbits were randomly divided into 99mTc-DTPA–, 99mTc-MAG3–, and 99m Tc-DMSA–injected groups. Experimental unilateral renal damage was induced by ligating a unilateral right ureter in 18 rabbits. Scintigraphic images were obtained at 2 and 5 h after intravenous injection of 99mTc-DMSA, or immediately after administration of 99mTc-DTPA or 99mTc-MAG3. For the dynamic images using 99mTc-DTPA and 99mTc-MAG3, rapid sequential images were obtained every 2 s for 30 images up to 1 min. The three groups presented different relative renal functions between the left normal and the right abnormal kidneys at 1, 2, 3, and 4 weeks post-ligation (p<0.05). However, the between-group comparisons showed no significant differences at any time. These results suggest that dynamic images of 99mTc-DTPA and 99mTc-MAG3 can be used to measure the relative renal function in place of the static image of 99mTc-DMSA.
In evaluating renal disease, it is important to consider the functional parameter that is reflected by the administered radiopharmaceutical, as well as the underlying disease state. Kidney scans, or renograms, are often performed to determine differential renal function for patients who are undergoing or being evaluated for urologic surgery (1). Use of 99mTc-labeled compounds, such as mercaptoacetyltriglycine (MAG3), diethylenetriamine pentaacetic acid (DTPA), and dimercaptosuccinic acid (DMSA), has made kidney scintigraphy one of the most useful nuclear medicine tools (2, 3).
99mTc-MAG3 is a tubular excreted radiopharmaceutical used for renal function and imaging, while 99mTc-DTPA is excreted by glomerular filtration. However, the exact mechanisms that underlie differences between the 2 tracers are not well understood (4). 99mTc-DTPA is almost completely excreted by glomerular filtration without tubular reabsorption. Thus, the small amounts of protein-bound 99mTc-DTPA can be used to obtain accurate glomerular filtration rate (GFR) measurements (1). Gates (5) found that the fractional renal uptake of intravenously (IV) administered 99mTc-DTPA, within 2 to 3 min of radiotracer arrival in the kidney, is proportional to the GFR. 99mTc-DMSA, 99mTc-DTPA and 99mTc-MAG3 have different renal uptake mechanisms, depending on the radiopharmaceutical administered. Therefore, these three agents can be used to compare the relative kidney uptake ratios at different periods of time: the relative renal functional characteristics reflected by 99mTc-DMSA, 99mTc-DTPA, and 99mTc-MAG3 can be used for comparative measurements. 99mTc-DMSA, as a static renal radiopharmaceutical, is considered to be the most dependable method to measure relative renal function (6, 7). But 99mTc-DMSA has some disadvantages, such as its relatively high radiation dose and time consumption compared to 99mTc-DTPA or 99mTc-MAG3. The aim of the present study was to measure by 99mTc-DTPA, 99mTc-MAG3, or 99mTc-DMSA in experimental rabbits with right ureteral obstruction.
Materials and Methods
Animals. Eighteen healthy male New Zealand white rabbits (age: 12 weeks, mass: 2.7-3.2 kg) were randomly divided into 3 groups of 6 animals each: 99mTc-DMSA–treated, 99mTc-DTPA–treated, and 99mTc-MAG3–treated groups. After general anesthesia, the proximal part of the right ureter in rabbits was ligated with 2-0 silk at 2 places adjacent to the renal pelvis. All protocols employed in this study were approved by the Animal Care Committee of Chungbuk National University, Republic of Korea.
Scintigraphic evaluation. Scintigraphy was performed before surgical intervention, and at 1, 2, 3, and 4 weeks post–ureteral ligation. After rabbits were administrated subcutaneous atropine (0.05 mg/kg), anesthesia was induced with IV xylazine (1.1 mg/kg) and maintained with IV ketamine (11 mg/kg). Data were obtained using a dual-head gamma camera (Infinia Hawkeye, GE Co., USA) equipped with computed tomography. Scintigraphy was performed at 2 and 5 h after ear vein IV injection of 3 mCi 99mTc-DMSA. The rabbit was positioned on the detectors, a bolus injection of 3 mCi 99mTc-DTPA or 99mTc-MAG3 was administrated into an ear vein, and the imaging was started immediately. Images were taken every 2 s for 1 min, and thereafter every 1 min for 25 min.
Measurement of regional radiopharmaceutical uptakes. To calculate the percentage of relative renal function, regions of interest (ROIs) were drawn around each kidney on both the anterior and posterior images of a 99mTc-DMSA static scan. 99mTc-DTPA or 99mTc-MAG3 dynamic scintigraphy images were summed for 2 to 3 min after starting the scan. ROIs were drawn around both kidneys and the backgrounds around the kidneys (Figure 1).
Statistical analysis. We compared the scintigraphic data for the three agents. Differences between the measured values at different times were evaluated using the Kruskal-Wallis test. Results are given as the mean±S.D. Significance was defined at the p<0.05 level. Differences between the left normal and the right abnormal kidneys were compared using the Wilcoxon signed rank test.
Results
All ROIs used were pea-shaped, and quantitative analyses included calculations for both the kidney and background. The left kidneys appeared to be normally sized in the scintigraphic images during the experimental periods, but the ligated right kidneys slowly became larger with time. Therefore, the left kidney ROIs were all drawn at the same size, but new right kidney ROIs were drawn each week.
Statistical analyses of the uptake ratios for 99mTc-DMSA, 99mTc-DTPA, and 99mTc-MAG3 are shown in Table I. 99mTc-DMSA, 99mTc-DTPA, and 99mTc-MAG3 uptakes in the right kidney were lower than those in the left kidney after surgical intervention. However, no significant difference was observed in the between-group comparison of 99mTc-DMSA, 99mTc-DTPA, and 99mTc-MAG3.
Discussion
A non-invasive means for determining individual renal function would be advantageous for surgical intervention or for the medical management of renal disease. These methods can be performed with different radiopharmaceuticals, such as 99mTc-DMSA, 99mTc-DTPA, or 99mTc-MAG3. 99mTc-DMSA enters the proximal tubular cell either by glomerular filtration and subsequent reabsorption or by direct uptake from the peri-tubular capillaries. 99mTc-DMSA is largely bound to serum proteins (8). Following IV administration, 99mTc-DTPA is rapidly distributed throughout the extracellular fluid space, where it is promptly cleared from the body by glomerular filtration (9). Excretion of 99mTc-MAG3 by the kidney is greater than that of 99mTc-DTPA (4).
The imaging provided by each agent reflects different renal functional parameters (10, 11). Although all of these methods accurately measure renal functional parameters, the agents do present some differences due to their distinct biological properties (1, 12), such as their renal excretion mechanisms, renal cell retention of radioactive material, and bound plasma-protein and plasma clearance levels (8, 13). As a static renal agent, 99mTc-DMSA is considered the most reliable method to measure relative renal function (14) and the most appropriate tracer for renal cortical imaging (15). Previous studies have revealed the effect of various parameters on renal disease, including age, duration between diagnosis and bacterial therapy initiation, and the presence of urinary anomalies, recurrent infections, or bladder dysfunctions (16).
We compared the renal uptakes measured using the above radiopharmaceuticals in experimentally unilateral ureteral-ligated rabbits. We observed no marked differences between the 99mTc-DMSA, 99mTc-DTPA, or 99mTc-MAG3 agents in terms of visualization of the pathological focus or image quality. The relative renal function for each of the three agents was similar in rabbits with unilateral ureteral obstruction. We conclude that renal function measurements using 99mTc-DTPA and 99mTc-MAG3 dynamic scintigraphs can be used to simultaneously measure the GFR. Acknowledgement This work was supported by a research grant of the Chungbuk National University, Republic of Korea, in 2009.
Footnotes
- Received February 12, 2010.
- Accepted February 22, 2010.
- Copyright © 2010 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved