Comparison of absolute renal uptake by using Tc-99m MAG-3 and Tc-99m DMSA.

PURPOSE: The purpose of this study is to compare the value of absolute renal uptake (ARU %) in patients by using Tc-99m MAG-3 and Tc-99m DMSA scan. MATERIAL AND METHODS: Absolute renal uptake is calculated using Tc-99m MAG-3 and Tc-99m DMSA in renal scintigraphy, Itoh and Tauex kidney depth methods used, respectively. n = 40 adult patients of both genders were included. All patients underwent Tc-99m MAG-3 and Tc-99m DMSA, respectively. RESULTS: The values of ARU (%) were calculated separately in selected patients n = 40, (left = 17, right = 23 normal functioning kidneys) by MAG-3 and DMSA. Absolute renal uptake (%) of Tc-99m MAG-3 in left kidneys was found to be 15.2 ±â€…3.4, with spilt renal function 79.2 ±â€…14.7 and ARU (%) in right kidneys 16.2 ±â€…3.4 with spilt renal function 77.5 ±â€…19. Absolute renal uptake of Tc-99m DMSA in left kidneys was 17.5 ±â€…3.2 and in right kidneys 17.9 ±â€…4.5 with spilt renal function 81.8 ±â€…10.7 and 79.3 ±â€…13.8 for left and right kidney, respectively. Statistical analysis showed strong Pearson correlation. CONCLUSION: Absolute renal uptake % was found to be more reliable in cases of bilateral compromised kidneys. ARU (%) calculated by Tc-99m MAG-3 solely can be used as predictor of renal function. The use of Tc-99m MAG-3 has more advantages than Tc-99m DMSA alone in renal scintigraphy as dynamic scintigraphy gives less radiation burden to patient, more information regarding renal function, and shorter stay time at hospital in comparison to static renal imaging. SRF % is less reliable than ARU (%).

Preclinical Evaluation of 99mTc-MAG3-5-Fab Targeting TREM2 in Lung Cancer Mouse Models: A Comparison with 99mTc-MAG3-5-F(ab')2.

Triggering receptor expressed on myeloid cells-2 (TREM2), which is expressed on the surface of tumor-associated macrophages (TAMs), has been found to play a major role in the diagnosis and treatment of tumors. TREM2 expression is significantly upregulated in tumor tissues, and therefore, targeting TREM2 for tumor imaging may be of value. Previously, we performed TREM2 targeting imaging by using 68Ga-NOTA-COG1410 or a 124I-labeled monoclonal antibody (mAb) and F(ab')2 in mouse models of colon and gastric tumors. However, some of the shortcomings of these probes (i.e., the high uptake of 68Ga-NOTA-COG1410 in the liver, the difficulty of obtaining iodine-124, and the long half-life of iodine-124) have hindered their clinical use. Herein, we sought to synthesize novel molecular probes targeting TREM2 that are more conducive to clinical translation, eliminating the interference of isotope availability and in vivo probe biodistribution issues. Therefore, we established A549 cell lines with negative human TREM2 (hTREM2) expression (GFP tag; hTREM2- A549) or upregulated hTREM2 expression (GFP tag; hTREM2+ A549) using lentiviral transfection and confirmed these with Western blotting and immunocytochemistry. We then prepared a mouse anti-human TREM2 (5-mAb) by immunizing with the hTREM2 antigen. The antibody fragments 5-F(ab')2 and 5-Fab were prepared from 5-mAb, and 99mTc-MAG3-5-F(ab')2 and 99mTc-MAG3-5-Fab were then synthesized with excellent stability and specificity. 99mTc-MAG3-5-F(ab')2 had a slightly higher in vitro affinity than 99mTc-MAG3-5-Fab (Kd = 3.32 ± 0.05 nmol versus 4.62 ± 0.85 nmol). 99mTc-MAG3-5-F(ab')2 and 99mTc-MAG3-5-Fab both showed excellent specificity: after adding a 100-fold precursor, the two probes binding to the cells were almost blocked. In vivo pharmacokinetics showed that the distribution and elimination half-lives of 99mTc-MAG3-5-Fab (T1/2α = 1.25 ± 0.30 min and T1/2ß = 21.98 ± 2.80 min, respectively) were significantly reduced compared to those of 99mTc-MAG3-5-F(ab')2 (T1/2α = 2.64 ± 0.37 min and T1/2ß = 86.55 ± 26.86 min, respectively). In micro single-photon emission computed tomography/computed tomography (micro-SPECT/CT) imaging, the tumor was clearly displayed at 1 h after 99mTc-MAG3-5-Fab injection, while the blood background was extremely low at 3 h, and the probe was mainly excreted through the kidneys and biliary tract. 99mTc-MAG3-5-F(ab')2 uptake was also detected at the tumor site, although the blood background was consistently high. The biodistribution results were consistent with the micro-SPECT/CT imaging results. 99mTc-MAG3-5-Fab could clearly display hTREM2+ A549 tumors in a short time (1 h) with low uptake in nontumor organs and tissues and thus has clinical application prospects.

Transport mechanism and affinity of [99mTc]Tc-mercaptoacetyltriglycine ([99mTc]MAG3) on the apical membrane of renal proximal tubule cells.

Technetium-99m-labeled mercaptoacetyltriglycine ([99mTc]MAG3) is widely used for evaluation of transplanted kidneys, diagnosis of tubular necrosis, and scintigraphic studies of tubular function. [99mTc]MAG3 is a substrate for organic anion transporter (OAT)1 and OAT3 on the basolateral membrane side for renal secretion. We investigated the transport mechanism and affinity of [99mTc]MAG3 on the apical membrane of renal proximal tubule cells for renal secretion. Adenosine triphosphate-binding cassette (ABC) transporters for renal secretion of [99mTc]MAG3 were examined using ABC transporter vesicles expressing multiple drug resistance 1 (MDR1), breast cancer resistance protein (BCRP), multidrug resistance-associated protein (MRP)2, and MRP4. MK-571, a MRP inhibitor, was applied to measure the Km and Vmax of MRP2 and MRP4 in a vesicle transport assay. Single photon emission computed tomography (SPECT) was performed in normal rats and MRP2-deficient Eisai hyperbilirubinuria rats (EHBR) using [99mTc]MAG3 with and without MK-571. [99mTc]MAG3 uptake in adenosine triphosphate was significantly higher than that in adenosine monophosphate in vesicles that highly expressed MRP2 and MRP4. The affinity of [99mTc]MAG3 for MRP4 was higher than that for MRP2. Renal secretion via MRP2 and MRP4 was identified by comparing normal and EHBR rats with and without MK-571 on SPECT. [99mTc]MAG3 is transported via MRP2 and MRP4 on the apical membrane of renal proximal tubule cells. The affinity of MRP4 is higher than that of MRP2. SIGNIFICANCE STATEMENT: [99mTc]MAG3, widely used for evaluation of transplanted kidneys, diagnosis of tubular necrosis, and scintigraphic studies of tubular function, is transported via MRP2 and MRP4 on the apical membrane of renal proximal tubule cells. The affinity of MRP4 is higher than that of MRP2.

Normal Values of Renal Function measured with 99mTechnetium Mercaptoacetyltriglycine SPECT in Mice with Respect to Age, Sex and Circadian Rhythm.

AIM: The aim of this study is to present normal values for 99mtechnetium mercaptoacetyltriglycine renal uptake kinetics as a function of age, sex and circadian rhythm in mice using multi-pinhole SPECT. METHODS: Dynamic multi-pinhole SPECT semistationary acquisitions consisting of 10 20 s frames followed by 25 50 s frames began prior to intravenous injection of 50 MBq in 12 female (F) and 12 male (M) C57BL/6N mice. Each mouse had follow-up imaging at 1, 3, 6, 12 and 22 months of age. To assess physiological changes related to circadian rhythm, animals were imaged during light (sleeping phase, SP) and dark conditions (awake phase, AP). Renal excretion time activity curves were analysed to determine maximum time to peak uptake (Tmax). RESULTS: There was an age-related effect on renal Tmax. In one-month-old mice median Tmax (1.8 min) occurred later than in 3-month-old mice (1.7 min; p = 0.035). Thereafter, mice showed continuously increasing time to renal Tmax up to an age of 22 months (2.3 min; p < 0.001). Female mice showed a significantly later renal Tmax than males (F 2.1 min, M 1.7 min; p < 0.001) from 3 months onwards. An effect of circadian rhythm on renal uptake was also observed with borderline relevance. Pooled results for all animals showed that renal Tmax appeared at a later timepoint after injection during SP (2.0 min) than during AP (1.8 min; p = 0.019), while in age and sex matched animal groups no significant differences were observed. CONCLUSION: This study showed that kidney function in mice is dependent on age and sex, whereas circadian rhythm does not cause a significant effect. Therefore, age and sex should be considered as important study design considerations for renal scintigraphy in mice, while the impact of circadian rhythm seems negligible. ZIEL:: Ziel dieser Studie war die Erhebung von Normwerten für die Nieren-Uptake-Kinetik von 99mTechnetium-Mercaptoacetyltriglycin Multipinhole SPECT in Abhängigkeit von Alter, Geschlecht und circadianem Rhythmus bei der Maus. METHODEN: Bei 12 weiblichen (F) und 12 männlichen (M) C57BL/6N Mäusen wurden unmittelbar vor intravenöser Injektion von 50 MBq 99mTc-MAG3 dynamische semistationäre Multipinhole-SPECT-Akquisitionen von 10 Frames à 20 s gefolgt von 25 Frames à 50 s gestartet. Jede Maus wurde im Altersverlauf mit 1, 3, 6, 12 und 22 Monaten untersucht. Um physiologische Veränderungen bezüglich des circadianen Rhythmus zu erfassen, wurden die Tiere während der Hellphase (Schlafphase, SP) sowie der Dunkelphase (Wachphase, AP) untersucht. Die Nierenfunktion ist als Zeit-Aktivitäts-Kurve dargestellt und die Zeit bis zum Maximum (Tmax) als Median in Minuten aufgeführt. ERGEBNISSE: Generell zeigte sich ein altersabhängiger Einfluss auf Tmax. Bei 1 Mo alten Tieren erfolgte Tmax (1,8 min) später als mit 3 Mo (1,7 min; p = 0,035). Im weiteren Altersverlauf zeigten die Mäuse einen kontinuierlich späteren Zeitpunkt von Tmax bis 22 Mo (2,3 min; p < 0,001). Weibchen zeigten ein signifikant späteres Tmax als Männchen (F = 2,1 min, M = 1,7 min; p < 0,001) ab einem Alter von 3 Monaten. Für den circadianen Rhythmus wurde ein nicht eindeutiger Effekt beobachtet. Wenn alle Tiere zusammengefasst wurden, erfolgte Tmax während der SP (2,0 min) später als während der AP (1,8 min; p = 0,019) während sich in den alters- und geschlechtsgetrennten Gruppen keine signifikanten Unterschiede nachweisen ließen. SCHLUSSFOLGERUNG: Diese Studie zeigte einen deutlichen Einfluss von Alter und Geschlecht auf die Nierenfunktion bei der Maus während der circadiane Rhythmus keinen eindeutigen Effekt aufwies. Deshalb sollten bei Nierenstudien mit Mäusen die Faktoren Alter und Geschlecht berücksichtigt werden, während der circadiane Rhythmus vernachlässigbar erscheint.

Comparison of the renal dynamic scan performed with 99mTc-L,L-EC and 99mTc-MAG3 in children with pelviureteric junction obstruction.

The aim was to compare the renal dynamic scan (RDS) performed with technetium-99-L,L-ethylene dicysteine (Tc-L,L-EC) and technetium-99-mercaptoacetyltriglycine (Tc-MAG3) in children with pelviureteric junction (PUJ) obstruction. A retrospective study was carried out and children with PUJ obstruction who had RDS performed with both Tc-L,L-EC and Tc-MAG3. Children with any intervention in between the two scans or a gap of more than 2 months in between renal scans were excluded. The dose of each radiotracer used was 0.1 mCi/kg (3.7 MBq/kg), with a minimum dose of 1 mCi (37 MBq). RDS was performed using the F+0 protocol. The differential renal function, Tmax, T1/2, drainage pattern, and hepatic uptake of the radiotracer were recorded and compared. A Bland-Altman plot was used to assess agreement between the two radiotracers. Sixteen children were included in the study. A total of 18 obstructed and 14 normal renal units were available to us for study. The values of differential renal function as well as Tmax and T1/2 of the two radiotracers were in agreement. In three obstructed kidneys in which T1/2 on Tc-MAG3 was greater than 20 min, Tc-L,L-EC showed T1/2 values of 13.3 min or less. Tc-L,L-EC showed nonobstructive drainage in three patients who had shown partial obstruction on Tc-MAG3 scan. The hepatic uptake of Tc-L,L-EC was also lower compared with Tc-MAG3. To conclude Tc-L,L-EC is a useful radiotracer for the evaluation of children with PUJ obstruction, with better assessment of drainage and lower hepatic uptake compared with Tc-MAG3.

Utility of MAG3 scintigraphy with the use of a 2 min uptake parameter in the assessment of postsurgical renal transplant complications.

OBJECTIVE: Major complications including acute tubular necrosis or rejection may occur after renal transplantation. We use a semiquantitative parameter, 2 min uptake (2MU), as part of Tc mercaptoacetyltriglycine (MAG3) scintigraphy for transplant evaluation. The aim of this study were (a) to examine the utility of Tc MAG3 scintigraphy in the assessment of postsurgical complications using the renal biopsy as the gold standard and (b) examine for any correlation with 2MU with serum creatinine (sCr) at 3 and 12 months. MATERIALS AND METHODS: We retrospectively reviewed all Tc MAG3 studies at our institution between July 2015 and June 2016, alongside available renal ultrasound, biopsy, and sCr results. RESULTS: A total of 105 patients fulfilled the inclusion criteria. 30/105 patients underwent biopsy less than 7 days of the Tc MAG3 study. Within this 7 day cohort, the negative predictive value for rejection with normal perfusion on Tc MAG3 study was 79% and the positive predictive value for rejection with abnormal Tc MAG3 perfusion was 9%. There was a weak negative correlation between 2MU and 3-month sCr (R=-0.358, P<0.001), and 2MU and 12-month sCr (R=-0.348, P<0.001). CONCLUSION: Although normal perfusion on Tc MAG3 scintigraphy study has a reasonable negative predictive value for rejection, abnormal Tc MAG3 perfusion is not useful in the differentiation of rejection from moderate to severe acute tubular necrosis. The 2MU parameter showed no additional benefit in the identification of rejection, but appeared to have a weak negative correlation with the 3-month and 12-month sCr, and may thus play a role in the prediction of longer term graft function.

Drugs interacting with organic anion transporter-1 affect uptake of Tc-99m-mercaptoacetyl-triglycine (MAG3) in the human kidney: therapeutic drug interaction in Tc-99m-MAG3 diagnosis of renal function and possible application of Tc-99m-MAG3 for drug development.

INTRODUCTION: Renal uptake of Tc-99m-MG3 involves organic anion transporter (OAT). Treatment with drugs showing OAT affinity might interfere with renal uptake of Tc-99m-MAG3, leading to misinterpretation in Tc-99m-MAG3. This study was conducted to discuss a possible drug interference with Tc-99m-MAG3 diagnosis on OAT sites. METHODS: Renal uptake and plasma clearance of Tc-99m-MAG3 were analyzed in healthy volunteers under control and OAT1 and OAT3 related drug treatment conditions. An in vitro uptake study using OAT1 or OAT3 expressing cells was also conducted. RESULTS: Both PAH and probenecid treatment induced delays in Tc-99m-MAG3 clearance from blood, and reductions in the renal uptake clearance. As a result, the normalized effective renal plasma flow estimated from Tc-99m-MAG3 clearance was significantly underestimated, whereas the glomerular filtration rate estimated from plasma creatinine levels was unchanged. The transport activity of Tc-99m-MAG3 was higher in OAT1-expressing cells than in OAT3-expressing cells. CONCLUSION: Drugs with OAT1 affinity affect the renal uptake of Tc-99m-MAG3 and blood clearance. This might cause misinterpretation of functional diagnosis of the kidney using Tc-99m-MAG3.

Effect of the NSAID diclofenac on 99mTc-MAG3 and 99mTc-DTPA renography.

UNLABELLED: Renal function and disease are commonly evaluated by radionuclide studies. The choice of radiopharmaceutical agent for various studies is crucial for proper interpretation. (99m)Tc-mercaptoacetyltriglycine ((99m)Tc-MAG3) is excreted almost exclusively by the renal tubules, whereas (99m)Tc-diethylenetriamine pentaacetic acid ((99m)Tc-DTPA) is predominantly excreted by glomerular filtration. The present study compared the effect of the nonsteroidal antiinflammatory drug (NSAID) diclofenac, which is the most commonly used drug to relieve kidney pain, on the kinetic behavior of administered (99m)Tc-MAG3 and (99m)Tc-DTPA in experimental animals. METHODS: Two groups of 12 New Zealand White rabbits ((99m)Tc-MAG3 and (99m)Tc-DTPA) were used for the renography. Each rabbit served as its own control. The animals were given 60 mL of saline intravenously 30 min before each renographic study. A baseline study (control) was done by injecting 48 MBq (1.3 mCi) of (99m)Tc-MAG3, and renography was performed. Two days later, a single intravenous dose of diclofenac (2 mg/kg) (treated animals) was given, and after 20 min, (99m)Tc-MAG3 renography was performed. This procedure was repeated for the (99m)Tc-DTPA group after administration of 96 MBq (2.6 mCi) of the tracer. Dynamic images (as 2-s frames for the first minute and 30-s frames for the next 30 min on a 64 × 64 matrix) were acquired using a γ-camera equipped with a low-energy high-resolution collimator interfaced with a computer. Regions of interest were drawn over the whole kidneys. Time-activity curves were generated from the region of interest. Time to peak activity (T(max)), time from peak to 50% activity (T(1/2)), and the uptake slope of each kidney were calculated from the renograms for control and treated rabbits. RESULTS: Administration of diclofenac shifted the experimental renogram curves to the right, compared with the control curves, indicating that there was a delayed renal uptake of the 2 tracers and clearance of the radioactivity. The calculated average values of T(max) for control and treated rabbits using (99m)Tc-MAG3 were 1.8 ± 0.5 and 6.35 ± 0.4 min, respectively, whereas those of (99m)Tc-DTPA were 3.4 ± 0.4 and 18.2 ± 2 min, respectively. The T1/2 for control and treated rabbits for (99m)Tc-MAG3 were 3.2 ± 0.07 and 6.6 ± 0.07 min, respectively, whereas those for (99m)Tc-DTPA were 10.1 ± 1 and 35 ± 4 min, respectively. The differences were statistically significant (P < 0.05). CONCLUSION: This study showed that diclofenac delayed both T(max) and T1/2. The NSAID-induced kinetic changes were considerably greater for (99m)Tc-DTPA than for (99m)Tc-MAG3. On the basis of these findings, it is suggested that (99m)Tc-MAG3 be used to perform renography for studies involving the use of NSAID administration to decrease any change that may occur due to the type of tracer and not to the condition of the kidney.

Pharmacokinetic alteration of (99m)Tc-MAG3 using serum protein binding displacement method.

INTRODUCTION: When a radiopharmaceutical is simultaneously administered with a medicine that has high affinity for the same plasma protein, the radiopharmaceutical is released at higher concentrations in blood, leading to enhanced transfer into target tissues. This is known as the serum protein binding displacement method. In this study, we investigated the pharmacokinetic alteration of technetium-99m-labeled mercaptoacetylglycylglycylglycine ((99m)Tc-MAG3) using the serum protein binding displacement method. METHODS: Rat and human serum protein binding rates of (99m)Tc-MAG3 were measured by ultrafiltration with or without displacers of human serum albumin (HSA) binding sites I and II (200µM and 400µM loading). Male Wistar rats were injected with (99m)Tc-MAG3 (740kBq/0.3mL saline) via the tail vein, and biodistribution was assessed at 2, 5, 10 and 15min. Dynamic whole-body images were obtained for (99m)Tc-MAG3 (11.1MBq/0.3mL saline)-injected rats, with or without HSA displacers. RESULTS: (99m)Tc-MAG3 strongly bound to HSA (87.37%±2.13%). Using HSA site I displacers, the free fraction of (99m)Tc-MAG3 increased significantly (1.20 to 1.47 times) when compared with controls. For biodistribution and imaging, rapid blood clearance was observed with bucolome (BCL) loading, which is an HSA site I displacer. With BCL loading, peak times for rat renograms were respectively shifted from 240s to 110s, and from 170s to 120s. CONCLUSIONS: We found that (99m)Tc-MAG3 bound to the HSA binding site I. It was confirmed that pharmacokinetic distribution of (99m)Tc-MAG3 is altered by presence of BCL, which leads to increases in the free fraction of (99m)Tc-MAG3, and BCL produced rapid blood clearance and fast peak times on rat renograms. The serum protein binding displacement method using (99m)Tc-MAG3 and BCL, a safe displacer for humans, may be applicable to clinical study and lead to better diagnostic images with shorter waiting times and lower radiation doses for patients.

Renal uptake of 99mTc-dimercaptosuccinic acid is dependent on normal proximal tubule receptor-mediated endocytosis.

UNLABELLED: (99m)Tc-labeled dimercaptosuccinic acid ((99m)Tc-DMSA) accumulates in the kidney cortex and is widely used for imaging of the renal parenchyma. Despite its extensive clinical use, the mechanism for renal targeting of the tracer is unresolved. Megalin and cubilin are cooperating receptors essential to the proximal tubule endocytic uptake of proteins from the glomerular ultrafiltrate. We have used megalin/cubilin-deficient mice produced by gene knockout to determine whether receptor-mediated endocytosis is responsible for the renal uptake of (99m)Tc-DMSA. METHODS: Control or megalin/cubilin-deficient mice were injected intravenously with 0.5 MBq of (99m)Tc-DMSA or (99m)Tc-mercaptoacetyltriglycine (MAG3). Whole-body scintigrams and the activity in plasma, urine, and the kidneys were examined 6 h after injection. The size and identity of (99m)Tc-DMSA-bound proteins in urine were analyzed by fractionation by centrifugation and separation by sodium dodecyl sulfate polyacrylamide gel electrophoresis, followed by autoradiography and mass spectrometry. RESULTS: No renal accumulation of (99m)Tc-DMSA was identified in scintigrams of megalin/cubilin-deficient mice. The renal accumulated activity of the tracer was reduced to 11.4% (± 2.5%, n = 7) of the normal uptake in control mice, correlating with a reduction in renal megalin/cubilin expression in knockout mice to about 10% of normal. The reduced renal uptake in megalin/cubilin-deficient mice was accompanied by an increase in the urinary excretion of (99m)Tc-DMSA. Size separation of the urine by ultracentrifugation and sodium dodecyl sulfate polyacrylamide gel electrophoresis demonstrated that in megalin/cubilin-deficient mice an increased amount of (99m)Tc-DMSA was excreted in an approximately 27-kDa form, which by mass spectrometry was identified as the plasma protein α1-microglobulin, an established megalin/cubilin ligand. CONCLUSION: (99m)Tc-DMSA is filtered bound to α1-microglobulin and accumulates in the kidneys by megalin/cubilin-mediated endocytosis of the (99m)Tc-DMSA protein complex. Renal accumulation of (99m)Tc-DMSA is thus critically dependent on megalin/cubilin receptor function and therefore is a marker of proximal tubule endocytic activity.

New chelation strategy allows for quick and clean 99mTc-labeling of synthetic peptides.

Analogues of bombesin have been synthesized in which a N2S2 (bis-mercaptoacetyl functionalized diaminopropionic acid) or a N3S (mercaptoacetyl-Gly-Gly-Gly) radiometal-chelating center has been incorporated that allows radiolabeling of these peptides with 99mTc without the need for conjugation or harsh reaction conditions. A mild radiolabeling is possible by using an acetyl-moiety as sulfur protecting group, which can be removed by mild hydroxylamine-treatment at room temperature before radiolabeling. Retained receptor binding is demonstrated in competitive binding experiments with 99mTc-radiolabeled peptides and PC-3 cells with bombesin receptors.

Tissular distributions and kinetics of two renal 99mTc-radiopharmaceuticals in rat.

A digital radioimager (RI), conventional radioautography (RA), and tracks microradioautography (MRA) were used to assess the biodistributions and kinetics of 99mTc-dimercaptosuccinic (99mTc-DMSA) and 99mTc-mercaptoacetyltriglycine (99mTc-MAG3) in rat at both macroscopic and microscopic levels. Three groups of male Wistar rats were studied. Using gamma-counting, kidney, liver, spleen and blood kinetics of both tracers were assessed in the three groups. Using RA and RI, renal slices were analyzed in group 1 the animals being sacrified from 2 to 60 min after injection of 99mTc-MAG3, and in group 2 the animals being sacrificed from 0.5 to 24 hr after injection of 99mTc-DMSA. Using MRA, renal slices were analyzed for 99mTc-DMSA (group 3). RA films and RI images displayed the variation with time of the cortical and medullary uptakes of the tracers. No regional heterogeneity within the different structures could be seen neither with RA films nor with MRA. The remaining activity in the blood 24 hr after injection of 99mTc-DMSA was evaluated. The tissular distributions of both tracer being homogenous, mean values of cortical uptake seems to be acceptable for dosimetric studies. Our results incite to use of 99mTc-MAG3 instead of 99mTc-DMSA when both tracers may be indicated.

Effect of protein binding on renal extraction of 131I-OIH and 99mTc-labeled tubular agents.

UNLABELLED: The clearance of 99mTc-mercaptoacetyltriglycine (MAG3) is less than the clearances of o-131I-iodohippurate (OIH) and 99mTc-labeled DD- and LL-ethylenedicysteine (EC). This difference could be associated with the lower affinity of MAG3 for the tubular transport receptor, but MAG3 is more highly protein bound than OIH and the EC isomers; protein binding could also be an important factor governing tubular extraction. To separate the effects of protein binding from tubular receptor affinity, the extraction fractions (EFs) of MAG3, OIH, and the DD, LL, and DL isomers of 99mTc-EC were measured in an isolated perfused rat kidney model using a protein-free perfusate and perfusates containing bovine serum albumin. METHODS: The right kidney was removed from the rat and perfused with modified Krebs-Henseleit buffers containing 7.5 or 2.5 g/dL bovine serum albumin or a protein-free perfusate. OIH was coinjected into the renal artery with each of the 99mTc-tracers. Protein binding was measured in each of the perfusates, and the venous outflow was collected to determine the EF. RESULTS: The protein binding of MAG3 in the albumin perfusates ranged from 87% to 95%, significantly higher than the 20%-34% range of protein binding observed with the three EC complexes (P < 0.05). In the 2.5 g/dL albumin perfusate, the EF of MAG3 was 44%, significantly less than the 57%-77% EF of the three EC complexes; in the 7.5 g/dL perfusate, the MAG3 EF fell to 18% versus 39%-45% for the EC complexes (P < 0.05). However, in the protein-free perfusate, the EF of MAG3 was 64%, equal to or higher than the 46%-62% EF of the three EC complexes. CONCLUSION: Protein binding modulates the tubular extraction of renal tracers. Protein binding and receptor affinity must be considered in the design of future renal radiopharmaceuticals as well as radiopharmaceuticals targeting other receptors.

Evaluation of the hepatobiliary excretion of technetium-99m-MAG3 and reconstitution factors affecting radiochemical purity.

UNLABELLED: Technetium-99-MAG3 is a renal tubular function agent. However, sporadic liver and gallbladder visualization have raised questions about kit stability, impurities and nonrenal routes of excretion. To address these issues, studies were conducted to optimize the labeling efficiency of the TechneScan MAG3 kit and to evaluate the hepatobiliary excretion of the MAG3 complex. METHODS: Thirty-six vials of the commercial formulation of 99mTc-MAG3 were prepared according to manufacturer's instructions and evaluated for radiochemical purity using two methods: a combination of high-performance liquid chromatography and paper chromatography (HPLC/PC); and the manufacturer's miniature chromatography system (Sep-Pak procedure). RESULTS: The labeling efficiency was significantly higher when the kit was reconstituted with 10 ml (96.6%) of saline versus 5 ml (91.4%) (p < 0.01). The radiochemical purity of the kits remained stable for up to 6 hr, but the purity determined by Sep-Pak averaged 2.5% higher than that determined by HPLC procedures (p < 0.01). Rat studies to evaluate renal and hepatobiliary elimination of MAG3 showed no difference in the %ID excreted into the urine by 60 min in all groups of animals studied. However, the %ID excreted into the bile was significantly higher for the kit formulation than the HPLC-purified MAG3, 9.9% versus 6.6% (p = 0.0475). CONCLUSION: The radiochemical purity of the TechneScan MAG3 kit can be improved by reconstituting with larger volumes. In addition, the studies in rats suggest that fasting or kit impurities may be a contributing factor to increased hepatobiliary visualization in patient studies.