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The dose to kidneys of newborns and 1-year old children was calculated using the MIRD methodology. In order to perform renal studies radiopharmaceutical like 99m Tc-DTPA, 99m Tc-MAG3 and 99m Tc-DMSA are used. Here, besides the anatomic and structure information of kidneys another data are provided in benefit of patient, however during the radioisotope decay emitted radiations delivers, totally or partially, their energy. Therefore is important to estimate the internal radiation dose of the organs. The largest dose to kidneys comes from the self-dose and it is due to the charged particles emitted during 99m Tc decay. From the three radiopharmaceutical here used the largest dose to kidneys is due to 99m Tc-DMSA, and the smaller dose is due to 99m Tc-MAG3., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objective: To determine the clinical value of visually assessed renal tissue transit time (TTT) in 99m Tc-mercaptoacetyltriglycine ( 99m Tc-MAG3) renography for patients undergoing pyeloplasty., Materials and Methods: Medical records of 164 patients who underwent dismembered pyeloplasty were retrospectively reviewed. Baseline and postoperative renal ultrasonography and 99m Tc-MAG3 renography were performed. Two urologists blinded to clinical data evaluated the renography and classified TTT as timely or delayed based on visualization of the tracer in the kidney pelvis between 2 and 10 minutes. Renal functional change after pyeloplasty was compared between patients in the timely and delayed groups., Results: A total of 126 patients (median age, 9 months) were evaluated after excluding patients with bilateral ureteropelvic junction obstruction, a single functioning kidney, duplicated ureter, or <3 months of follow-up. There were no differences between 89 patients with timely TTT and 37 patients with delayed TTT in mean preoperative hydronephrosis grade (3.7 vs 3.8) and pelvic diameter (3.1 cm vs 3.4 cm). Although the pre- and postoperative mean values of differential renal function (DRF) were significantly higher in the timely group than in the delayed group (47.2% vs 38.3% and 47.9% vs 44.6%), DRF change was greater in the delayed group (6.3% vs 0.6%). In multivariate analysis, delayed TTT was the only significant predictor of >5% improvement in renal function after pyeloplasty., Conclusion: Delayed TTT in 99m Tc-MAG3 renography was a significant predictor of renal functional improvement after pyeloplasty in ureteropelvic junction obstruction. Because substantial improvement of renal function is anticipated, we recommend immediate pyeloplasty in patients with delayed TTT and decreased DRF., (Copyright © 2017 Elsevier Inc. All rights reserved.)

A Technetium 99m Tc labeled lyophilized single component kit of N-N-ethylene-I-dicysteine (EC) is developed to replace multiple step kit developed by others. The aim of study is to formulate a radionuclide that is easy to prepare, has rapid plasma clearance, produce high quality images and is an affective alternative to radioiodine labeled orthoiodohippurate, which has been remained the physiological 'gold standard' since long time. To achieve this goal, the systematically varied key parameters such as pH, the use of reducing agents, stabilizers and additives are optimized to obtain maximum radiochemical purity and optimum biodistribution in non human and human primates. Various pH levels of EC showed equally good results in animal experiments but only pH 10 was suitable for human use. Dynamic and renal Scintigraphic studies are carried out with 99m Tc-EC at pH 8 in 12 volunteers and at pH 10 in 18 volunteers and compared with 99m Tc-MAG3, Background ratios, renograms, relative renal function and semi quantitative parameters are available in all studies. The background ratios (mean ± SD) at 30th minute are 0229±0.024 and 0.236±0.018 for 99m Tc-EC at pH 10 and 99m Tc-MAG3 respectively. The mean ± standard error of mean (SEM) values of TMAX and time to half activity (T12) for 99m Tc-EC (pH10) are 3.7±0.6 and 7.3±1.0 respectively while for 99m Tc-MAG3, they are 4.0±0.8 and 7.9±1.4 with p values 0.001 and 0.049 respectively. The values of relative renal function (RRF) for 99m Tc-EC and 99m Tc-MAG3 are 50.8±3.11 and 51.2±3.4 respectively with p value of 0.822. The residual activity at 25th minute (A25 / A MAX) and renal uptake are 0. 209±12.67±2.80 for 99m Tc-EC and 0.218±0.035 and 1053±2.98 for 99m Tc-MAG3 (p=0.031 an 0.0003) respectively. The correlation coefficient (R2) for TMAX, T 1/2 , A25/AMAX and renal uptake are 0.96, 0.69, 0.93 and 0.85 respectively.

Objective: This study aims to evaluate interobserver agreement on visual analysis of technetium-99m mercaptoacetyltriglycine (Tc-MAG3) renal tissue transit used for the evaluation of antenatal hydronephrosis., Materials and Methods: Thirty-eight Tc-MAG3 diuretic renograms were retrospectively collected between 1 and 31 December 2015. The 1-min reframed images were presented to four nuclear medicine consultants and to two nuclear medicine residents, one in the first year of the training program and the others in their fourth and final year. These observers were asked to classify the radiotracer cortical transit (normal/delayed) based solely on visual assessment of the images. For the interobserver agreement, modified Fleiss' kappa (κ) analysis for multiple raters was carried out. For both groups, percentages of agreement were also calculated., Results: A total of 69 kidneys were evaluated. All four nuclear medicine consultants agreed on the classification of 88.4% of the kidneys. When the agreement of at least three of the four observers was considered, the percentage of agreement reached 98.6%. The two nuclear medicine residents agreed on the classification of 69.6% of the kidneys. The modified Fleiss' κ-value was 0.88 (95% confidence interval: 0.79-0.95) for the group of nuclear medicine consultants, indicating almost perfect agreement. For the residents, it was 0.39 (95% confidence interval: 0.16-0.59), suggesting fair agreement., Conclusion: Our results seem to indicate that there is an almost perfect agreement in the qualitative identification of delayed cortical transit among physicians with experience at observing renographic images.

Peptide Receptor Radionuclide Therapy (PRRT) for the treatment of neuroendocrine tumors may lead to kidney deterioration. This study aimed to evaluate the suitability of 99mTc-mercaptoacetyltriglycine (99mTc--MAG3) clearance for the early detection of PRRT-induced changes on tubular extraction (TE). TE rate (TER) was measured prior to 128 PRRT cycles (7.6±0.4 GBq 177Lu-octreotate/octreotide each) in 32 patients. TER reduction during PRRT was corrected for age-related decrease and analyzed for the potential to predict loss of glomerular filtration (GF). The GF rate (GFR) as measure for renal function was derived from serum creatinine. The mean TER was 234 ± 53 ml/min/1.73 m² before PRRT (baseline) and 221 ± 45 ml/min/1.73 m² after a median follow-up of 370 days. The age-corrected decrease (mean: -3%, range: -27% to +19%) did not reach significance (p=0.09) but significantly correlated with the baseline TER (Spearman p=-0.62, p<0.001). Patients with low baseline TER showed an improved TER after PRRT, high decreases were only observed in individuals with high baseline TER. Pre-therapeutic TER data were inferior to plasma creatinine-derived GFR estimates in predicting late nephropathy. TER assessed by 99mTc-MAG3-clearance prior to and during PRRT is not suitable as early predictor of renal injury and an increased risk for late nephropathy., Competing Interests: CONFLICTS OF INTERESTS RAW has received the “YING” research grant from Novartis Pharma, Nürnberg, Germany. AW has received the “YING” research grant from Novartis Pharma, Nürnberg, Germany. All other authors declare no conflict of interests.

Aim: The sulfonamide group is widely used for bacterial diseases including kidney and urinary tract infections. The present study investigates the effect of a sulfa drug on kidney function and renography studies by using a radionuclide., Methods: Renography studies were performed on New Zealand white rabbits. Each rabbit was injected with 48.1 MBq technetium-99m mercaptoacetyltriglycine ((99m) Tc-MAG-3). Dynamic images were acquired using a gamma camera. Radioactivity time curves were generated from the regions of interest, time to peak activity (Tmax ) and time from peak to 50% activity (T1/2 ). Each rabbit served as its own control. The sulfa drug was given to these rabbits for 7 days (i.v injection 130 mg/kg daily in two divided doses; i.e. the single dose is 65 mg/kg), then dynamic images were acquired., Results: Treatment with sulfa shifted the experimental curves to the right of the control curves. This result showed that there was a delayed renal uptake of (99m) Tc-MAG-3 and its clearance. Calculated averages of Tmax were 2.2 ± 0.3 and 5.9 ± 0.5 min; while for T1/2 were 3.1 ± 0.3 and 8.4 ± 0.6 min for control and sulfa-treated rabbits, respectively (n = 20; P < 0.05)., Conclusion: Our results indicate that sulfa drug induced pharmacokinetic changes because of delaying both the Tmax and T1/2 . Sulfa drug has an effect on the reabsorption from the renal tubules and the excretion process of (99m) Tc-MAG-3 which is excreted almost exclusively by the renal tubules. Therefore, sulfa drug causes a deterioration in kidney function and an alteration on radionuclide renography., (© 2014 Asian Pacific Society of Nephrology.)

Background: To investigate functional aspects of silent ureteral stones with special focus on obstruction and its relationship to renal anatomy. The present study is the first investigation of renal excretory function in patients with silent ureteral stones., Methods: Patients with primarily asymptomatic ureteral stones underwent a mercapto-acetyltriglycine (MAG-3) renal scintigraphy prior to treatment, in addition to anatomic evaluation of renal units and serum creatinine levels. The primary outcome measure was the presence or absence of obstruction. Secondary outcome measures were kidney anatomy, grade of hydronephrosis, location of stones, stone size, and serum creatinine levels., Results: During a ten-year period, 14 patients (median age 52.6 years; range 37.3 to 80.7 years) were included in the study. The relative frequency of primarily asymptomatic ureteral stones among all patients treated for ureteral stones in the study period was 0.7%. Eleven renal units showed some degree of hydronephrosis while 3 kidneys were not dilated. On the MAG-3 scan, 7 patients had an obstruction of the ureter, 5 had no obstruction, and 2 had dysfunction of the kidney. A statistically significant correlation was established between the grade of obstruction and stone size (p = 0.02)., Conclusions: At the time of presentation, only 64.3% of the patients revealed an obstruction in the stone-bearing renal unit. The degree of hydronephrosis and renal function were very diverse in this subgroup of patients with ureteral stones. The onset of ureterolithiasis and the chronological sequence of obstruction remain unclear in patients who have never experienced symptoms due to their stones.

Several single sample methods for determination of (99m)Tc-mercaptoacetyltriglycine (MAG3) clearance are being used clinically. Kabasakal et al. proposed a similar formula for (99m)Tc-ethylenedicysteine (EC). This study was performed to compare his method with Bubeck et al. formula for (99m)Tc-MAG3 already in use. Twenty-eight subjects divided in two groups were registered which included 22 patients with various renal diseases (group-I) and six normal volunteers (group II). All subjects were studied twice using both the radiopharmaceuticals. The images and renogram parameters, that is TMAX and T1/2 of both the agents, were similar in all the subjects. The clearance of the (99m)Tc-EC was however considerably higher than (99m)Tc-MAG3 in both the groups (mean ± SEM =279 ± 14 ml min(-1)/1.73 m(2) versus 177 ± 15 ml min(-1)/1.73 m(2) in group-I and 377 ± 11.90 ml min(-1)/1.73 m(2) versus 238 ± 8.23 ml min(-1)/1.73 m(2) in group II). This difference was more pronounced in cases with reduced renal functions. Among the Effective Renal Plasma Flow (ERPF) values determined from EC and MAG3 clearances in six normal volunteers, four cases only in MAG3 had ERPF below the lower limit. This study has demonstrated superiority of single sample method for (99 m)Tc-EC clearance over its analogous method for (99m)Tc-MAG3., (© 2013 The Authors Clinical Physiology and Functional Imaging © 2013 Scandinavian Society of Clinical Physiology and Nuclear Medicine.)

In dynamic renal scintigraphy, the main interest is the radiopharmaceutical redistribution as a function of time. Quality control (QC) of renal procedures often relies on phantom experiments to compare image-based results with the measurement setup. A phantom with a realistic anatomy and time-varying activity distribution is therefore desirable. This work describes a pharmacokinetic (PK) compartment model for (99m)Tc-MAG3, used for defining a dynamic whole-body activity distribution within a digital phantom (XCAT) for accurate Monte Carlo (MC)-based images for QC. Each phantom structure is assigned a time-activity curve provided by the PK model, employing parameter values consistent with MAG3 pharmacokinetics. This approach ensures that the total amount of tracer in the phantom is preserved between time points, and it allows for modifications of the pharmacokinetics in a controlled fashion. By adjusting parameter values in the PK model, different clinically realistic scenarios can be mimicked, regarding, e.g., the relative renal uptake and renal transit time. Using the MC code SIMIND, a complete set of renography images including effects of photon attenuation, scattering, limited spatial resolution and noise, are simulated. The obtained image data can be used to evaluate quantitative techniques and computer software in clinical renography.

Objective: To explore the value of telomerase targeted radiolabeled small interference RNA (siRNA) in tumor imaging in vivo., Methods: Human telomerase reverse transcriptase (hTERT)-targeted and human gene non-targeted siRNAs were chemically synthesized. Through the conjugation with the chelator N-hydroxysuccinimidyl derivative of S-acetylmercaptoacetyltriglycine (NHS-MAG3), the siRNAs were radiolabeled with technetium-99m ((99m)Tc). HE staining and immunohistochemical staining were used to identify their pathological characteristics. 7.4 MBq of (99m)Tc-siRNAs were injected via the tail vein of hepatocarcinoma bearing mice. At 0.5, 1, 3, and 6 h post injection, the mice were laid on a face-up detector and imaged by single-photon emission computed tomography (SPECT), respectively. The ratio of radioactive counts in tumor to that in the contralateral equivalent region was calculated by drawing regions of interest (ROI) at each time point. After the administration of 7.4 MBq of (99m)Tc-siRNAs, the biodistribution (%ID/g) of tumors and blood was measured at the end of 2, 4 and 6 h. Statistical comparisons of the variables were performed by t-test., Results: The labeling efficiency reached 73.4% ± 3.0%. After purification, the radiochemical purity was no less than 92% and the specific activity was up to 25.9 GBq/μmol. HE staining showed pathological mitotic figure in the nucleus of the tumor cells. hTERT immunohistochemical staining showed deep brown dyed spots in the cell nucleus. hTERT-targeted (99m)Tc-siRNA administrated xenografts showed tumor images clearly after the administration, especially at 6 h. In contrast, (99m)Tc-control-siRNA showed no tumor image. The ratios of uptake in tumor to that in contralateral region of hTERT-targeted siRNA increased from 2.68 ± 0.21 to 5.86 ± 0.30 at 6 h, whereas those of control siRNA decreased from 1.55 ± 0.16 to 1.28 ± 0.12 (P<0.01). The biodistribution of tumors in the hTERT-targeted mice increased from 0.71 ± 0.14 to 0.97 ± 0.15 at 6 h, whereas that in the control mice decreased., Conclusion: (99m)Tc radiolabeled telomerase-targeted siRNA probe allows for noninvasive visualization of tumor telomerase in vivo.

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., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Acute kidney injury (AKI) is a well-recognized complication of minimal change nephrotic syndrome (MCNS). Previous reports support the concept that AKI associated with MCNS is reversible; however, information regarding the hemodynamic basis of AKI in MCNS is insufficient. We herein describe a case of AKI in a man with MCNS. In this case, monitoring the longitudinal changes in renal perfusion using serial Tc-99m-MAG3 renal scanning was beneficial for evaluating the pathophysiological background associated with the development of AKI. The potential impact of serial renal scanning in MCNS patients with AKI will also be discussed.

Purpose: To establish camera-based methods for estimating Tc-99m mercaptoacetyltriglycine (MAG3) clearance without blood sampling., Materials and Methods: The results of renal scintigraphy with Tc-99m MAG3 obtained from 160 patients were analyzed retrospectively. Eight renogram parameters were calculated for each patient based on the area under the renogram (area method) and slope of the renogram (slope method) using different periods for analysis (1-2 and 1-2.5 minutes for the area method; 0.5-1.5 and 0.5-2 minutes for the slope method) and different backgrounds for subtraction (perirenal and subrenal backgrounds). The 8 parameters were then correlated with MAG3 clearance measured by the single-sample methods proposed by Russell et al and Bubeck et al to determine the equation for the conversion of renogram parameters to clearance., Results: All 8 renogram parameters were highly correlated with clearance measured by the single-sample methods, and the obtained equations enabled the estimation of clearance from image data. Selection between the area and slope methods, between different periods for analysis, or between perirenal and subrenal backgrounds did not cause large differences in the estimation., Conclusion: The camera-based methods determined in the present study allow the estimation of MAG3 clearance with acceptable accuracy.

Mercaptoacetyltriglycine (MAG3) and dimercaptosuccinic acid (DMSA) labelled with technetium-99m belongs to standard renal radiodiagnostics. However, the renal transport mechanisms responsible for their high renal uptake have not been fully explained. In addition, no in vitro experimental study comparing the renal uptake of these radiopharmaceuticals at the cellular level has not been performed. The investigation compared the 99mTc-MAG3 and 99mTc-DMSA renal uptake using primary rat renal cells and evaluated contribution of active and passive transport processes to the renal accumulation. The renal cells were isolated from the rat kidneys by means of the two-phase collagenase perfusion method. The used experimental model showed to be useful tool for such type of investigation. The results documented significant quantitative and qualitative differences in the accumulation of 99mTc-DMSA and 99mTc-MAG3 in the rat isolated cells. The found experimental data indicated several times higher uptake of 99mTc-MAG3 than that found in 99mTc-DMSA. 99mTc-MAG3 cellular uptake was substantially decreased when active, energy-dependent processes were inhibited. However, 99mTc-DMSA accumulation in the renal cells demonstrated only a minor dependency on energy. These findings demonstrate a very different character of the membrane transport determining 99mTc-DMSA and 99mTc-MAG3 renal accumulation.

Objectives: To address the fact that a decrease in the relative renal uptake of 99mTc-mercaptoacetyltriglycine (MAG3) on serial MAG3 scans may indicate a loss of function and require a change in management by providing guidance as to what constitutes a meaningful change in serial relative function measurements as well determining the normal variation of other common MAG3 renogram parameters., Methods: A prospective study was conducted in 24 male urology patients with stable renal function. The mean age was 66.5 ± 7.9 (SD) years; the mean serum creatinine was 1.38 ± 0.57 (SD) mg/dL, and the MAG3 renal scans were performed a mean of 11 ± 8 days apart. Each MAG3 scan included a measurement of relative function as well as the time to maximum counts and 20 minutes to maximum count ratios for both cortical and whole kidney regions of interest., Results: The Pearson and intraclass correlations for the baseline and repeat measurements of relative renal function were both 0.98. Bland-Altman plots showed no bias between the baseline and repeat relative uptake measurements. The mean difference between 2 repeated measurements of the relative MAG3 uptake was 0.04 ± 2.88% (SD) for the left kidney and 0.08 ± 3.07% (SD) for the right kidney. Comparable results were obtained for the other renogram parameters., Conclusions: Measurements of relative renal uptake of MAG3 and common renogram parameters are highly reproducible; a decrease in relative uptake ≥7% (ie, 50%-43%) implies a loss in renal function., (Copyright © 2010. Published by Elsevier Inc.)

Renal function measurements using (99m)Tc-DTPA and (99m)Tc-MAG(3) dynamic scintigraphs were compared to those obtained using (99m)Tc-DMSA static scintigraphy. Eighteen experimental rabbits were randomly divided into (99m)Tc-DTPA-, (99m)Tc-MAG(3)-, 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 (99m)Tc-DMSA, or immediately after administration of (99m)Tc-DTPA or (99m)Tc-MAG(3). For the dynamic images using (99m)Tc-DTPA and (99m)Tc-MAG(3), 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 (99m)Tc-DTPA and (99m)Tc-MAG(3) can be used to measure the relative renal function in place of the static image of (99m)Tc-DMSA.

Three carbohydrate derivatives, MAG(3)-Gl, MAG(3)-Ga, MAG(3)-NG, were synthesized and radiolabeled in high yields. These substances were injected in health Swiss mice and their biodistribution were evaluated. Among them, (99m)Tc-MAG(3)-Ga displayed higher accumulation in hepatic tissue, due to the presence of specific receptors in the liver for this carbohydrate. Thus, the use of (99m)Tc-MAG(3)-Ga to assess hepatic function can be considered., (Copyright 2009 Elsevier Ltd. All rights reserved.)

Tc-99m cystine has been proved to be a good renal agent in animals for morphologic as well as the functional status of the kidney. In this study, we compared Tc-99m cystine with Tc-99m mercaptoacetyltriglycine, which is used for evaluation of renal function in normal patients, and those with various degrees of renal functional impairment. The clearance values and static images are compared with Tc-99m mercaptoacetyltriglycine. The results show that Tc-99m cystine has good radiopharmaceutical characteristics suitable for evaluation of both renal function as well as morphology.

This study was undertaken to explore and compare the radiochemical behavior and biological property of antisense oligonucleotide (ASON) labeled with Technetium-99m using two methods: N-hydroxysuccinimidyl S-acetylmercaptoacetyltriglycline (NHS-MAG3) versus hydrazino nicotinamide derivative (SHNH). After SHNH and NHS-MAG3 were synthesized, ASON was labeled with Technetium-99m using SHNH and NHS-MAG3 as a bifunctional chelator, separately. The stability in vivo and in vitro, the combination with plasma albumen of rabbit, the biodistribution in BALB/ C mice and the HT29 cellular uptake were compared between labeled compound 99mTc-SHNH-ASON, using SHNH as a bifunctional complex reagent, and 99mTc-MAG3-ASON, using NHS-MAG3 as a bifunctional chelator. The results revealed that the labeling rate and the stability of 99mTc-MAG3-ASON were evidently higher than that of 99mTc-SHNH-ASON (P < 0.05), the combination rate of 99mTc-MAG3-ASON with plasma albumen was markedly lower than that of 99mTc-SHNH-ASON (P < 0.05); the biodistribution of 99mTc-MAG3-ASON was markedly lower than that of 99mTc-SHNH-ASON in blood, heart, stomach and intestines (P < 0.05), slightly lower than that of 99mTc-SHNH-ASON in liver and spleen (P > 0.05), and markedly higher than that of 99mTc-SHNH-ASON in kidney (P < 0.05); the HT29 cellular uptake rates of 99mTc-MAG3-ASON was markedly higher than that of 99mTc-SHNH-ASON (P < 0.05). Therefore, the radiochemical behavior and biological property of 99mTc-MAG3-ASON labeled using NHS-MAG3 is better than that of 99mTc-SHNH-ASON labeled using SHNH.

The aim of this study is to explore the optimal labeling condition of technetium-99m labeled antisense oligonucleotides (ASON) DNA and sense oligonueleotides (SON) DNA against multi-drug resistance gene-1 (MIDR1) mRNA, to prepare its two-step icefrozen kits, and to perform the quality control of technetium-99m labeled ASON and SON DNAs and its two-step icefrozen kits. A 20 mer single-stranded ASON sequence and its SON sequence against MDR1 mRNA were synthesized respectively, both of the ASON and SON DNAs were uniform phosphorothioated for this investigation with a primary amine on the 5'-end via a six-carbon alkyl linker, and then were labeled with technetium-99m by conjugating with the bifunctional chelator S-Acetyl NHS-MAG3 to form ASON- and SON-MAC3 DNAs. The optimal labeling condition was explored by varying the amount of ASON- and SON-MAG3 DNAs, SnCl2.2H2O and buffer, the pH value in the reaction medium was also adjusted. The technetium-99m labeled ASON and SON DNAs' two-step icefrozen kits were developed. The radiochemical purities, labeling stability of ASON- and SON-MAG3 DNAs in vivo and vitro were measured, and stability of the two-step icefrozen kits were also studied. The recycled rates of ASON- and SON-MAG3 DNAs were over 70% (n >6), the two-step icefrozen kits of ASON- and SON-MAG3 DNAs were colourless ice crystal. The radiochemical purities of technetium-99m labeled ASON- and SON-MAG3 DNAs were over 92 %. The radiochemical purities were over 90% after stored at room temperature for 24 hours. The kits were stable within 6 months when stored at 0 degrees C, the radiochemical purities of technetium-99m labeled ASON- and SON-MAG3 DNAs were still over 90%. The two-step icefrozen kits of ASON- and SON-MAG3 DNAs were successfully developed. The radiochemical purities were all over 90%. The labeling method was simple, feasible and efficient with good stability.

Surgical ureteric injury is rare and often unsuspected for a long time. We present a child in whom an abdominal neuroblastoma was completely excised, but during surgery the left ureter was transected and anastomosed. One month later, during postoperative disease staging, abnormal (123)I-MIBG accumulation was observed in the left renal cortex and the left side of the abdomen. These findings were consistent with acute total obstruction and urinoma formation and were subsequently confirmed by renography and MRI. Despite treatment efforts, a significant amount of left renal mass and function were lost over the following months. These unusual findings are new additions to the literature regarding potential false-positive interpretations of (123)I-MIBG scans.

Unlabelled: The expression of human telomerase reverse transcriptase (hTERT) is present in most malignant cells (>85%) but is undetectable in most normal somatic cells. Visualization of hTERT expression using radionuclide targeting can provide important diagnostic information in malignant tumors. The overall aim of this study was to evaluate whether (99m)Tc-radiolabeled antisense oligonucleotide (ASON) targeting hTERT messenger RNA (mRNA) can be used for imaging of hTERT expression in vivo., Methods: One 18-mer antisense or sense uniformly phosphorothioate-modified oligonucleotide targeting hTERT mRNA was radiolabeled with (99m)Tc through the bifunctional chelator N-hydroxysuccinimidyl derivative of S-acetylmercaptoacetyltriglycine (S-acetyl NHS-MAG3). Then the radiolabeled probe was characterized in vitro. Reverse transcription-polymerase chain reaction (RT-PCR) was performed to assay the mRNA level after proliferating cells had been incubated with the antisense and sense probes. (99m)Tc-MAG3-ASON or (99m)Tc-MAG3-SON was injected intravenously in mammary tumor-bearing BALB/c nude mice. Biodistribution and in vivo imaging was performed periodically. All data were analyzed by statistical software., Results: The labeling efficiencies of (99m)Tc-MAG3-ASON/SON reached 76% +/- 5% (n = 5) within 15-30 min at room temperature, the specific activity was up to 1,850 kBq/mug, and the radiochemical purity was >96% after purification. (99m)Tc-MAG3-ASON showed complete stability at room temperature and in fresh 37 degrees C human serum. In comparison with (99m)Tc-MAG3-SON, (99m)Tc-MAG3-ASON preserved the capacity to bind living hTERT-expressing cells specifically and to inhibit the expression of hTERT mRNA significantly as well as ASON. In nude mice bearing hTERT-expressing MCF-7 xenografts, tumor radioactivity uptake of (99m)Tc-MAG3-ASON after injection was significantly higher than that of (99m)Tc-MAG3-SON after injection (P < 0.05). The hTERT-expressing xenografts were clearly imaged at 4-8 h noninvasively after injection of (99m)Tc-MAG3-ASON, whereas the xenografts were not imaged at any time after injection of (99m)Tc-MAG3-SON., Conclusion: This in vivo study provides evidence that (99m)Tc-MAG3-ASON targeting hTERT mRNA can be used as a potential candidate for visualization of hTERT expression in carcinomas.

Gallbladder uptake is occasionally encountered with commonly used nonhepatobiliary radiopharmaceuticals. Identification of the biliary tract by a nonhepatobiliary agent can identify disease, such as uptake of labeled white blood cells. However, in most cases, gallbladder uptake of nonhepatobiliary tracers is not due to pathology in these cases. It is important to avoid attributing gallbladder uptake to disease in the gallbladder or adjacent anatomic structures. We present 3 cases of unexpected gallbladder tracer uptake and provide a review of the literature describing incidental gallbladder uptake on nonhepatobiliary nuclear medicine studies. The potential for misdiagnosis and the steps taken to avoid this are discussed.

A 25-y-old man with horseshoe kidney was referred for diuretic-augmented renal scintigraphy. Single-detector dynamic posterior imaging was performed and revealed asymmetric retention of radiotracer in the left collecting system. Renal scintigraphy was repeated with a modified protocol. Dynamic imaging was performed this time using dual-detector acquisition of both anterior and posterior data. Thereafter, pregravity and subsequently postgravity static images were obtained in both anterior and posterior projections. This second study showed near-complete emptying of the left collecting system. This case illustrates the utility of using simultaneous anterior and posterior imaging and geometric mean calculations for functional analysis and also highlights the value of physiologic maneuvers to augment the traditional diuretic challenge.

Purpose: Expression of human epidermal growth factor receptor type 2 (HER2) in malignant tumours possesses well-documented prognostic and predictive value. Non-invasive imaging of expression can provide valuable diagnostic information, thereby influencing patient management. Previously, we reported a phage display selection of a small (about 7 kDa) protein, the Affibody molecule Z(HER2:342), which binds HER2 with subnanomolar affinity, and demonstrated the feasibility of targeting of HER2-expressing xenografts using radioiodinated Z(HER2:342). The goal of this study was to develop a method for (99m)Tc labelling of Z(HER2:342) using the MAG3 chelator, which was incorporated into Z(HER2:342) using peptide synthesis, and evaluate the targeting properties of the labelled conjugate., Methods: MAG3-Z(HER2:342) was assembled using Fmoc/tBu solid phase peptide synthesis. Biochemical characterisation of the agent was performed using RP-HPLC, ESI-MS, biosensor studies and circular dichroism. A procedure for (99m)Tc labelling in the presence of sodium/potassium tartrate was established. Tumour targeting was evaluated by biodistribution study and gamma camera imaging in xenograft-bearing mice. Biodistribution of (99m)Tc-MAG3-Z(HER2:342) and (125)I-para-iodobenzoate -Z(HER2:342) was compared 6 h p.i., Results: Synthetic MAG3-Z(HER2:342) possessed an affinity of 0.2 nM for HER2 receptors. The peptide was labelled with (99m)Tc with an efficiency of about 75-80%. Labelled (99m)Tc-MAG3-Z(HER2:342) retained capacity to bind specifically HER2-expressing SKOV-3 cells in vitro. (99m)Tc-MAG3-Z(HER2:342) showed specific tumour targeting with a contrast similar to a radioiodinated analogue in mice bearing LS174T xenografts. Gamma camera imaging demonstrated clear and specific visualisation of HER2 expression., Conclusion: Incorporation of a mercaptoacetyl-containing chelating sequence during chemical synthesis enabled site-specific (99m)Tc labelling of the Z(HER2:342) Affibody molecule with preserved targeting capacity.

Objectives: To determine the value and limitations of technetium-99m mercaptoacetyltriglycine (MAG3) clearance measurements obtained using a gamma camera (camera-based MAG3 clearance), a prospective study was conducted to evaluate the reproducibility of camera-based MAG3 clearance compared with that of conventional creatinine clearance., Methods: A total of 24 male patients with stable renal function were entered into the study. The mean age was 66.5 +/- 7.9 years, and the mean serum creatinine was 1.38 +/- 0.57 mg/dL. MAG3 renal scans and 24-hour creatinine clearance measurements were performed 11 +/- 8 days apart. A camera-based MAG3 clearance was obtained at each MAG3 scan; no blood samples were required. Bland-Altman plots were constructed to assist in data analysis., Results: The Pearson correlation for the first and second camera-based MAG3 clearances (mean 151 versus 158 mL/min/1.73 m2, respectively) was 0.965 compared with 0.729 for the two creatinine clearance measurements (mean 62 versus 72 mL/min/1.73 m2, respectively). Even with the omission of two outliers, the creatinine clearance would have to change by 58.2% compared with the baseline measurement before the clinician could be confident the change exceeded the error of measurement. In contrast, the change required for the camera-based MAG3 clearance was 30.8%., Conclusions: The results of this study have demonstrated that MAG3 clearance obtained using a camera-based technique shows greater precision than the conventional creatinine clearance and is superior to the conventional creatinine clearance for monitoring changes in renal function.

Objective: Specific quantitative measurements have been recommended to assist in the interpretation of technetium-99m mercaptoacetyltriglycine (MAG3) renal studies. Our objective was to define the sex- and age-specific normal ranges for these recommended parameters., Materials and Methods: Data were obtained from a retrospective analysis of 106 subjects who were evaluated for kidney donation. The MAG3 clearance was calculated using a common camera-based method. The relative uptake, prevoid/postvoid and postvoid/maximum count ratios were determined using whole-kidney regions of interest (ROIs). Time to peak, time to half-peak, 20 min/maximum and 20 min/2-3 min count ratios were determined for cortical and whole-kidney ROIs. Residual urine volume was calculated on the basis of the pre- and postvoid bladder counts and voided urine volume., Results: The mean camera-based MAG3 clearance was 321 +/- 69 mL/min/1.73 m2, essentially the same as the mean plasma sample MAG3 clearance in comparable populations. The percentages of relative uptake in the right and left kidneys were 49% and 51% +/- 4%, respectively; no difference was seen between men and women. Cortical values were lower than the whole-kidney values (p < 0.001); the mean cortical 20 min/maximum count ratio was 0.19 (SD, 0.07 and 0.04 for right and left kidneys, respectively). The mean postvoid/maximum whole-kidney count ratio was < 0.1, and the mean postvoid residual bladder volume was < 30 mL., Conclusion: Normal limits adjusted for age and sex have been established. Applying normal ranges to quantitative MAG3 parameters may assist in the interpretation of MAG3 scintigraphy and facilitate appropriate patient management.

This case demonstrates the effect of exercise on the clearance of Tc-99m MAG3 in a patient with renal insufficiency status post-liver transplant. Even after furosemide administration, the tracer was retained in the kidneys after exercise. This is in contrast to normal clearance demonstrated on a baseline study performed 3 days previously.

The efficacy of three radiopharmaceuticals, 99mTc-diethylenetriaminepentaacetic acid (99mTc-DTPA), 99mTc-dimercaptosuccinic acid (99mTc-DMSA), and 99mTc-mercaptoacetyltriglycine (99mTc-MAG3), for renal imaging was examined in 16 corn snakes (Elaphe guttata guttata). All snakes received the radiopharmaceutical via an intracardiac injection. The kidneys could not be visualized in the three snakes that received 99mTc-DTPA or in the three snakes that received 99mTc-DMSA, but were well delineated in all 10 snakes receiving 99mTc-MAG3. These snakes were anesthetized and a dynamic frame mode acquisition was obtained for 30 min immediately following injection. A 60 s single static frame mode image was then obtained with the snake in a curled position. Two of the 10 snakes that received 99mTc-MAG3 were removed from further analysis because of suspected pericardial injections. Of the remaining eight snakes, the mean (+/- SD) renal uptake was 25 +/- 9.8% or 24 +/- 9.7%, with or without correction for residual injection site activity, respectively. Correction for remaining radioactivity in the heart does not appear to be necessary if it is less than 10% of the total dose. 99mTc-MAG3 provided consistently high quality images of the kidneys and further studies are warranted to evaluate its sensitivity for detecting decreased function in snakes with renal disease.

Aim: The perfusion time-activity curve on DTPA renal scintigraphy shows a peak and plateau pattern which is usually absent or less marked when using tubular agents such as MAG3. The exact mechanism that results in this difference between the two tracers is not well understood. A descending pattern on MAG3 has been proposed to be due to decreased extraction. In this study we compared the diagnostic utility of perfusion patterns obtained with DTPA and MAG3 among patients with renal allograft dysfunction., Materials and Methods: This study included 48 patients with renal allograft dysfunction and 18 recipients with normal graft function. Every recipient had renal scintigraphy with Tc-99m MAG3 and Tc-99m DTPA 1 day apart. The second phase of the perfusion curve after the initial rise was classified as ascending, flat, or descending. In patients with a descending curve on DTPA study, we calculated the ratio of counts at peak perfusion to that at plateau (P:PL). Impaired perfusion was based on a deterioration of the peak-to-plateau pattern on DTPA and the presence of a flat-descending curve on MAG3., Results: In patients with dysfunction, impaired perfusion was observed in 77% of DTPA and in 54% of MAG3 studies. A flat-descending curve on MAG3 was present in 44% of patients with normal graft function. By MAG3, 67% of acute rejection and 28% of chronic allograft nephropathy (CAN) cases showed deteriorated perfusion. The corresponding values for DTPA were 67% and 94%, respectively. A flat-ascending pattern on DTPA was more frequent in CAN than it was in acute rejection (33% and 17%, respectively)., Conclusion: The sensitivity of DTPA perfusion pattern for diagnosing dysfunction was significantly greater than that for MAG3. Our results suggest that the major determinant of a curve pattern on DTPA or MAG3 study is the extraction relative to perfusion. Thus for patients with CAN, extraction is higher relative to perfusion, resulting in a lower P:PL ratio or an ascending curve on DTPA. Although the extraction of DTPA is less than that of MAG3, this level of extraction renders DTPA more sensitive to serial changes in renal function and pathophysiological mechanisms related to kidney 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.

We conjugated mercaptoacetyltriglycine (MAG(3)) to rh-annexin V to permit radiolabeling with (99m)Tc in an effort to decrease the high kidney and liver accumulation observed for (99m)Tc-labeled Hynic-annexin V. The 36-kDa protein was conjugated at a 5:1 molar ratio with NHS-MAG(3) in HEPES buffer pH 7.8 at room temperature, then quenched with glycine and purified by dialysis. The biopotency of the resulting MAG(3)-annexin was similar to that of Hynic-annexin as determined by a sensitive red blood cell membrane affinity binding assay and a surface plasmon resonance (SPR) assay. The (99m)Tc radiolabeling of MAG(3)-annexin resulted in radiochemical yields of 90% under mildly basic pH conditions. Biodistribution data in normal mice clearly showed a significant decrease in kidney and liver uptake at 1 h postinjection for the (99m)Tc MAG(3)-annexin compared to the (99m)Tc Hynic-annexin (from 24% ID to 4% ID for the liver, and 45% ID to 15% ID for the kidneys, respectively). Autoradiography of the kidneys showed retention of radioactivity in the collecting tubules following administration of both labeled annexins. The (99m)Tc MAG(3)-annexin biodistribution was also characterized by a lower retention of radioactivity in the whole body, but with small intestine accumulation over fivefold higher than observed with (99m)Tc Hynic-annexin. These findings show a definite improvement in renal and hepatic clearance of the MAG(3) radioligand. However, due to the increased radioactivity uptake in the small intestines, the early in vivo detection of ongoing apoptosis in the lower abdomen might be more difficult with (99m)Tc MAG(3)-annexin. Nevertheless, (99m)Tc MAG(3)-annexin may be an attractive alternative to (99m)Tc Hynic-annexin for the in vivo imaging of phosphatidylserine receptors.

Effect of probenecid on pharmacokinetics of 99mTc-mercaptoacetylytriglycine (99mTc-MAG3) in dogs was investigated before (control), and after 15 min and 24 h of i.v. injection of probenecid (20 mg/kg). Plasma concentration-time profiles of 99mTc-MAG3 were described with a two-compartment open model. Plasma 99mTc-MAG3 clearances (Clp, ml/min/kg) were 7.9 +/- 0.5, 3.3 +/- 0.5 and 4.8 +/- 1.3 in control, 15 min and 24 h after probenecid administration respectively. Similarly, the biological half-lives at elimination phase (t(1/2), h) were 0.61 +/- 0.09, 0.79 +/- 0.11 and 0.74 +/- 0.12, and volumes of distribution at steady state (Vdss, L/kg) were 0.29 +/- 0.04, 0.20 +/- 0.05 and 0.25 +/- 0.06 respectively. The prolonged biological half-life and decreased Vdss decreased Clp significantly. Clp was a function of plasma probenecid concentration based on Michaelis-Menten kinetics. The maximum Clp inhibition (Imax) by probenecid and the plasma probenecid concentration that induced 50% of Imax (I50) were estimated to be 72 +/- 12% and 13 +/- 8 microg/ml respectively. This means that the rest (about 28%) of the Clp is not blocked by probenecid alone, suggesting the possibility of another route(s) of elimination or renal transporters which are independent from probenecid. Moreover, inter-species correlation between Clp of 99mTc-MAG3 and body weight are discussed.

Unlabelled: To investigate the feasibility of in vivo imaging study of atherosclerotic plaque and restenosis using antisense probe, we evaluated the uptake kinetics of radiolabeled oligonucleotides to the messenger RNA (mRNA) of proliferating cell nucleus antigen (PCNA) in vascular smooth muscle cells (VSMCs) and the effect on gene expression., Methods: The antisense oligonucleotide to PCNA was radiolabeled with (99m)Tc through bifunctional chelator mercaptoacetyltriglycine (MAG(3)). The labeling efficiency was assessed by Sephadex G25 chromatography. The radiochemical purity, in vitro stability, and ability of the labeled antisense oligonucleotide to hybridize to its complement were analyzed by Sep-Pak C18 column chromatography. The uptake kinetics of (99m)Tc-labeled antisense oligonucleotide and sense oligonucleotide were studied in VSMCs in log and plateau phases. To study whether the antisense probe can hybridize to a respective sequence on the whole PCNA mRNA strand after radiolabeling, we performed reverse-transcriptase polymerase chain reaction to assay the PCNA mRNA level after the VSMCs had been incubated with the (99m)Tc-labeled antisense oligonucleotide and sense oligonucleotide., Results: The labeling efficiency of (99m)Tc-MAG(3)-antisense oligonucleotide was 60.1% (n = 5), the specific activity was 1,960 kBq/microg, and the radiochemical purity was more than 95% after purification. (99m)Tc-MAG(3)-antisense oligonucleotide was stable in vitro and retained the ability to hybridize with its complementary chain. Antisense oligonucleotide showed significantly higher accumulation than sense oligonucleotide in log phase, with peak values of 15.2% +/- 0.58% and 5.6% +/- 0.42%, respectively (P < 0.05). No significant difference was found between uptake of antisense oligonucleotide and uptake of sense oligonucleotide in plateau phase (P > 0.05), but higher accumulation of antisense oligonucleotide was found in log phase than in plateau phase (P < 0.05). The retention rate of antisense oligonucleotide in log phase was much higher than that of sense oligonucleotide (79.6% +/- 0.96% vs. 59.8% +/- 0.75%, P < 0.05) at 240 min. The 2 probes did not significantly differ in plateau phase (P > 0.05). The efflux of antisense oligonucleotide was obviously slower in log phase than in plateau phase (P < 0.05). Compared with (99m)Tc-MAG(3)-sense oligonucleotide, (99m)Tc-MAG(3)-antisense oligonucleotide could inhibit the expression of PCNA mRNA significantly., Conclusion: This in vitro study in VSMCs provided evidence that the (99m)Tc-labeled antisense oligonucleotide to PCNA can be used for in vivo imaging of atherosclerotic plaque and restenosis in further study.

Rationale and Objectives: The purpose of this study was to evaluate the influence of hydration status upon renogram patterns and renal physiological parameters and clarify the differences between DTPA and MAG3 studies in normal volunteers., Material and Methods: The study populations were 22 kidneys of 11 volunteers with no history of hypertension or renal disease with normal serum creatinine levels. They were 6 men and 5 women aged from 24 to 48 yrs (mean age: 33.4 yrs). Renal scintigraphies with both 185 MBq (5 mCi) of Tc-99m DTPA and Tc-99m MAG3 were performed after dehydration (urine specific gravity > 1.025) and adequate hydration (urine specific gravity < 1.010) in each subject at least with a 5-7-day interval. Renograms were generated from the whole kidney and cortical ROIs. We analyzed the clearance, renogram pattern, mean transit time, time to maximum activity, time from maximum activity to half activity, and residual cortical activity. Paired t-test and Wilcoxon signed rank test were used as statistical analysis methods. Statistical analysis was considered significant at p < 0.05., Results: In the dehydrated state, with Tc-99m DTPA and whole kidney ROI, parameters such as time to maximum activity, time from maximum activity to half activity, residual cortical activity, and mean transit time were delayed as compared to parameters in the adequately hydrated state, but the clearance was not changed. With the cortical ROI, the changes of parameters due to dehydration were partially offset. There were insignificant differences between most parameters of Tc-99m DTPA and Tc-99m MAG3 with the whole kidney and cortical ROIs., Conclusions: Dehydration may bring about a false positive curve pattern on renograms which can be prevented or minimized by using the cortical ROI. There were insignificant differences between most parameters of Tc-99m DTPA and Tc-99m MAG3.

Aim: We evaluated the long-term residual renal function after donor nephrectomy using 99mTc-mercaptoacetyltriglycin (MAG3)-clearance., Donors, Methods: Altogether 49 kidney donors were examined using 99mTc-MAG3-clearance after nephrectomy for donation to a relative (m:f = 11:38; age 55+/-27 years). The donors were examined 16+/-8 years postoperatively (1.5-26 years). 42 donors (86%) showed normal creatinine values, whereas the other seven (14%) exhibited slightly elevated levels. 20 donors were examined pre- and postoperatively and compared intraindividually. The kidney function was compared to the age adapted normal values of healthy persons with two kidneys (67-133% of age related mean)., Results: After nephrectomy all donors showed a normal perfusion, good secretion, merely physiological intrarenal transit and a normal elimination from the kidneys. The 99mTc-MAG3-clearance was 69+/-15% of the normal mean value of healthy carriers of two kidneys regardless of the gender. 20 donors with a preoperative examination showed a significantly reduced total renal function from 84+/-15% of the mean normal value preoperatively to 60+/-15% postoperatively (p <0.0005). 15 donors of this group exhibited a significant functional increase of the residual kidney from 40% initially to 60% after nephrectomy (p = 0.003). No correlation was found between the initial-99mTc-MAG3-clearance measured prior to nephrectomy and the clearance levels after nephrectomy. Also, no correlation between the preoperative 99mTc-MAG3-clearance and the postoperative serum creatinine values could be observed. Altogether, 22% of the donors (11/49) developed arterial hypertension 10+/-8 years after donation (1-23 years). This corresponds to the normal age prevalence of hypertension in the carriers of two kidneys. Three donors suffered from arterial hypertension prior to the operation., Conclusion: Kidney donors with normal or slightly elevated creatinine values postoperatively show a 99mTc-MAG3-clearance value of 69% of the mean value of healthy carriers of two kidneys. This may serve as a reference value for healthy carriers of one kidney. In our study we demonstrated a good compensation of the contralateral kidney via renal scintigraphy by means of 99mTc-MAG3-clearance.

To investigate a new kind of tumor tracer 99mTc-YIGSR developed from a five amino structure (YIGSR) of the Laminin -chain, which can bind to the laminin receptors of tumor specifically, and radiolabeled with MAG3. (1) Preparation of the 99mTc-YIGSR probe: with S-Acetly-NH3-MAG3 as the chelator and with proper reductants YIGSR was labeled with 99mTc; (2) Cell culture and viability measurement: EAC was maintained in RPMI 1640 supplemented with calf serum; the trypan blue exclusion was applied to calculate the cell viability; (3) Study of the cell dynamic: The EAC's uptake of 99mTc-YIGSR and 99mTc-MIBI was observed at 37 degrees C and 22 degrees C, respectively. (1) The labeling efficiencies of 99mTc-YIGSR and 99mTc-MIBI were (62 +/- 3)% and (96 +/- 2)%, respectively; (2) The cell viability was declined with time of incubation; (3) At 37 degrees C, the EAC'S uptake of 99mTc-YIGSR and 99mTc-MIBI reached the peak of (43.16 +/- 2.4) % and (24.4 +/- 1.8) % at 60 min, respectively; and at 22 degrees C, the highest uptake was (26.5 +/- 2.1) % and (9.47 +/- 1.9) % at 60 min, respectively. The in vitro study suggests that 99mTc-YIGSR is superior to 99mTc-MIBI in cell uptake and has potential value in tumor imaging.

Background: Conflicting results have been published concerning the reproducibility of Tc-99m MAG3 clearance. The aim of the study was to reevaluate again this reproducibility on a large prospective series of healthy volunteers., Material and Methods: Fifty subjects underwent three successive tests performed at 1-week interval. The physiological conditions were controlled as much as possible and all experimental measurements were rigorously double-checked. Renal clearances were calculated using single sample algorithms., Results: Thin layer chromatography demonstrated a radiochemical purity of more than 92% (mean 93.8%; SD 1.6%; range 92.0-96.4%). The mean (and SD) of 44th minute plasma concentrations for the three successive measurements were respectively 1.8 +/- 0.4, 2.1 +/- 0.4 and 1.9 +/- 0.4 (%dose/liter). The mean changes (and S.D. of differences) between two tests were 0.26 +/- 0.29, -0.08 +/- 0.5 and 0.18 +/- 0.30 respectively between tests 1 and 2, tests 1 and 3, and tests 2 and 3. Using Bubeck's algorithm, the mean clearance values (ml/min/1.73 m2) were 268.8 (range 201.4-336.8), 247.2 (range 170.5-290.3), and 262.8 (range 187.4-340.0) respectively for the first, second and third measurements. Using Russell's approach, the mean clearance values were respectively 314.9 (range: 208.7-441.7), 280.1 (range: 167.5-358.6), and 305.4 (range: 189.5-447.9)., Conclusions: High differences were observed between the 3 tests. Using Russell s formula, the SD of differences between two tests was respectively 35.8, 47.7 and 57.7 ml/min/1.73 m2 between tests 1 and 2, tests 1 and 3, and tests 2 and 3. Whether such a large variability is acceptable in clinical practice depends solely on what the clinician is expecting.

Aim: Renal function is usually determined by means of creatinine-clearance, and of serum Cystatin C, the latter with increasing frequency. The present study analyses, whether the diagnostic accuracy of (99m)Tc-MAG(3) clearance is comparable to that of these modern serologic methods., Patients, Methods: 71 consecutive adult Caucasian patients (42 female, 29 male; age 50 +/- 16 yrs., range 20-83) who were referred to a nuclear medicine department for determination of bilateral renal function with (99m)Tc-MAG(3) were included. Following sufficient hydration, 10 ml of blood were taken for determination of Cystatin C and creatinine in serum prior to i.v. injection of the radiotracer. According to the recommendations of the National Kidney Foundation, glomerular filtration rate (GFR) was calculated from serum creatinine using either Cockcroft & Gault and Modification of Diet in Renal Disease (MDRD) study equation. These estimates of GFR served as reference. Cystatin C is a low molecular protein produced by all nuclear cells and is eliminated to 85 % by glomerular filtration. Analysis of (99m)Tc-MAG(3) clearance was performed by means of Bubeck's formula., Results: Linear regression analysis produced Pearson's correlation coefficients of r = 0.68 and r = -0.69 for the comparison of either Cystatin C and (99m)Tc-MAG(3) clearance with the Cockcroft & Gault equation. The comparison of Cystatin C and (99m)Tc-MAG(3) clearance with MDRD study equation resulted in correlation coefficients of r = 0.755 and r = -0.77. None of these differences were significant. The exclusion of renal impairment or the detection of an at least moderate renal impairment revealed again no significant differences between Cystatin C and (99m)Tc-MAG(3) clearance., Conclusions: Cystatin C and (99m)Tc-MAG(3) clearance are equally suited to exclude renal impairment or to detect a relevant renal impairment. Differences between both procedures are more likely a result of the applied reference method.

Unlabelled: Because bacteriophages (phages) have a natural specificity for bacteria, it may be possible to develop radiolabeled phages as infection-specific agents., Methods: The M13 phage was radiolabeled with (99m)Tc via mercaptoacetyltriglycine and purified by polyethylene glycol precipitation. After radiolabeling, the phage was tested for binding at 1, 5, and 10 min to Escherichia coli strain 2537, E. coli strain 25922, and Staphylococcus aureus strain 29213. The radiolabeled phage was also tested for specificity in mouse models that had received a subcutaneous injection of either live (infection/inflammation model) or heat-inactivated (inflammation model) cultures in a thigh. The labeled phage (10(9) plaque-forming units, 1-3.7 MBq) was administered either within 20 min (to minimize the contribution from inflammation) or 3 h after induction. The animals were killed 3 h later., Results: The radiochemical purity of the labeled phage exceeded 95% by strip chromatography using instant thin-layer chromatography/acetone and paper/saline. Binding of the labeled phage to each of the 3 bacterial strains in vitro was immediate, reaching a maximum at 1 min. However, the percentage bound was significantly higher (P = 0.0008) for E. coli 2537 than for either of the other 2 bacteria (84% vs. 41% and 48%). Furthermore, binding to E. coli 2537 was unchanged at 10 min, whereas binding to both E. coli 25922 and S. aureus decreased to 33%. At 3 h in vivo, the ratio of target thigh to normal thigh was significantly higher (P < or = 0.017) in the infection/inflammation model (2 to 2.5 fold) than in the inflammation model (1.5 to 1.8) and therefore suggestive of increased accumulation specific to infection. The difference was slightly more pronounced in animals that received labeled phage at 20 min after inoculation, showing a ratio of 2.3 for infected thigh to normal thigh and a ratio of 1.6 for inflamed thigh to normal thigh. Although absolute uptake was lowest in the infection/inflammation thigh of mice infected with E. coli 2537, this finding was presumably due to the therapeutic effect of the phage on this strain., Conclusion: Radiolabeled bacteriophages should be further investigated as potential agents for specific imaging of infection.

Objectives: To evaluate the function of the remaining kidney after nephrectomy for renal cell cancer by technetium-99m-mercaptoacetyltriglycine (99mTc-MAG3) renal scintigraphy., Methods: We evaluated 30 consecutive patients who were undergoing unilateral radical nephrectomy by 99mTc-MAG3 scintigraphy. All patients underwent three consecutive 99mTc-MAG3 scintigraphy studies. The first study was performed before nephrectomy, the second 1 month after surgery, and the third 1 year after surgery. At these times, the serum creatinine levels were also evaluated., Results: The mean preoperative MAG3 clearance of the remaining kidney of the 30 patients was 155.4 mL/min/1.73 m2. The mean MAG3 clearance of the remaining kidney had increased to 209.2 mL/min/1.73 m2 by 1 month after nephrectomy, and the average percentage increase was 39.5%. After 1 year, it had increased to 211.3 mL/min/1.73 m2, with a 40.5% average percentage increase. The preoperative MAG3 clearance of the remaining kidney was inversely correlated with the percentage of increase in MAG3 clearance of the remaining kidney. Abnormal serum creatinine levels (greater than 1.3 mg/dL) were more common after nephrectomy, occurring in 6 patients at 1 month and in 5 patients at 1 year postoperatively. In all 6 patients with elevated creatinine levels, the preoperative MAG3 clearance of the remaining kidney was less than 150 mL/min/1.73 m2., Conclusions: Adaptive hyperfunction occurs soon after nephrectomy that is not associated with age or sex and continues for at least 1 year. A greater compensatory response is produced in patients with more severe renal deterioration. Using 99mTc-MAG3 scintigraphy, we may be able to predict postoperative renal function.

Introduction: It has been suggested that renal retention function can be estimated by differentiation of the Patlak-Rutland plot., Aim: To evaluate the error resulting from this method., Methods: A total of 5800 renograms were generated by convolving real input functions with artificial retention functions. Ten bi-exponential plasma disappearance curves of Tc mercaptoacetyltriglycine (Tc-MAG3) with varying renal clearances served as input functions and 580 retention functions with mean transit time between 3 and 60 min, and variable ratios of minimal to mean transit time served as original retention functions. The retention function was estimated by differentiation of the Patlak-Rutland plot of each renogram. A variant of this retention function was calculated by setting negative values to zero., Results: Minimal transit time was estimated correctly in all cases but the recovered retention function systematically underestimated the original, and negative values were observed. Mean transit time was underestimated with a difference ranging from -22.05 to -0.06 min. By setting the negative values to zero, a less important underestimation was observed which ranged from -13.37 to 0.00 min. Maximal transit time was underestimated systematically with a difference ranging from -22.05 to 0.00 min. All differences were influenced by mean transit time, renal clearance and ratio of minimal to mean transit time., Conclusion: Estimation of the renal retention function by differentiation of the Patlak-Rutland plot results in systematic and sometimes important underestimations. By setting the negative values of the recovered retention function equal to zero, important but still partial improvement can be obtained.

Objective: Nephron-sparing surgery is a treatment in which a part of a diseased kidney is resected and some parenchyma of the kidney is spared. Impairment of spared renal parenchyma after the surgery may cause prolonged prarenchymal retention in renal scintigraphy with Tc mercaptoacetyltriglycine (Tc-MAG3). The aim of this study was to determine whether or not parenchymal retention of Tc-MAG3 is prolonged after nephron-sparing surgery., Methods: Twenty-two patients underwent a total of 29 Tc-MAG3 studies within 1 year after nephron-sparing surgery. In 17 patients (23 examinations) who had bilateral kidneys, the presence of diffuse prolongation of parenchymal retention was determined for the operated kidney. In all patients, the presence of regional prolongation around the surgical margin was assessed., Results: Diffuse prolongation was observed in four of 10 examinations performed within 1 month after surgery and in none of 13 examinations performed later than 1 month after surgery. Regional prolongation was shown in 10 of 14 examinations performed within 1 month after surgery and in three of 15 examinations performed later than 1 month after surgery. In five patients who were studied both prior to and later than 1 month after surgery, regional prolongation was noted on the first study. On the second study, regional prolongation was improved and initial renal uptake around the surgical margin was intensified., Conclusions: Renal parenchymal retention of Tc-MAG3 is frequently prolonged in the early period after nephron-sparing surgery. Renal scintigraphy with Tc-MAG3 may aid in characterizing acute renal damage after nephron-sparing surgery.

Unlabelled: One of the potential limitations in the usefulness of both renal output efficiency (ROE) and normalized residual activity (NORA) is their residual dependence on total renal function. The purpose of this study was to present and examine a new quantitative method whereby the effects of this dependence may be removed., Methods: The analytic method involves the determination of a retention function using an unconstrained matrix algorithm deconvolution technique followed by reconvolution with a chosen standard input function to yield a new secondary renal activity time (A/T) curve from which normalized values of ROE and NORA, denoted as N&#95;ROE and N&#95;NORA, respectively, can then be obtained using conventional definitions. The method has been applied in a series of 50 patient studies, which had been acquired using (99m)Tc-mercaptoacetyltriglycine (99(m)Tc-MAG3) and a standard F+18 furosemide protocol, with values of the ratio of plasma clearance to plasma volume (C/V) in the range 0.013-0.242 min(-1)., Results: Pre- and postnormalization values of NORA, calculated at 30 min after injection, showed a significant difference in mean values (paired t test; P < 0.001), with a maximum observed difference, DeltaNORA(30), of -4.82 (-482%) and with a SD on the paired differences, DeltaNORA(30), of 0.56 (56%) or 0.63 (63%) if background subtraction on the input function (BSIF) had been performed. In contrast, corresponding values of ROE showed a nonsignificant difference in means (P > 0.05) and a SD on the paired differences, DeltaROE(30), of 3.7% or 3.2% with and without BSIF, respectively. The normalized parameters N&#95;ROE and N&#95;NORA were found to be strongly linearly correlated (r = -0.99; P < 0.001), in agreement with theoretical predictions., Conclusion: These results suggest that renal function affects NORA significantly more than ROE. The effects can be corrected by our normalization technique, resulting in equivalent values of normalized ROE and normalized NORA.

Objective: To explore the radiolabeling property of oligonucleotide with 99mTc using NHS-MAG3 as a bifunctional chelator., Methods: Three 15-base single-stranded amine-derivitized oligonucleotides, which were antisense(ASON), sense(SON) and mismatched oligonucleotides(MON) of c-myc oncogene mRNA, were coupled with NHS-MAG3 and labeled with 99mTc. The labeled oligonucleotide was purified by Sephadex G25 column chromatogram, then the stability was evaluated. The labeling efficiency of ON-MAG3 was assessed 15 days, 1 month and 2 months after storage at -20 degrees C. The binding rate of 99mTc-ON with plasma protein was measured by the trichloroacetic acid precipitation method., Results: The average labeling efficiency of 99mTc-ASON, 99mTc-SON and 99mTc-ON was 68.41%, 66.24% and 69.38% respectively, and the radiochemical purity was 96.98%, 95.34% and 94.62%. 99mTc-ON was stable when placed at room temperature or incubated in human serum at 37 degrees C. The labeling efficiency of ON-MAG3 did not significantly change 2 months after storage at -20 degrees C. The plasma protein binding rate of 99mTc-ON was lower than 13%., Conclusion: 99mTc-ON labeled with NHS-MAG3 method showed superior radiochemical characteristics. The labeling efficiency and radiochemical purity were desirable. The label was stable in serum and the binding with plasma protein was low. 99mTc-ON could be a sort of potential radiopharmaceutical for in vivo applications.

Objective: To improve the estimation of 99mTc mercaptoacetyltriglycine clearance in the renal uptake method by optimizing the conditions of renal depth, background, threshold for renal boundary determination, and time interval for integrating renal counts., Methods: Dynamic renal imaging was performed in 232 patients with dual energy window acquisition (main, 140 +/- 14keV; sub, 122.5 3.5keV). For drawing renal regions of interest (ROIs), cut-off methods with 50% and 70% of the highest renal pixel counts were used. For drawing the backgrounds, circumferential and lateral-inferior quadrant peri-renal ROIs were used. For setting the time interval, periods of 1-2, 1-2.5, 1.5-2.5, 1.5-3 and 2-3 min post-injection were used. For determining renal depth, three methods of a theoretical exponential function using scatter fraction, Tønnesen's formula, and linear combination of scatter fraction and Tønnesen's formula were used. The scatter fraction was calculated using the counts in renal ROIs in the two energy windows. Using every combination of these conditions, renal uptake was calculated. As a reference, one-sample clearance was calculated from a blood sample taken at 30 min post-injection following Bubeck's formula. According to the methods for estimating renal depth, three non-linear regression models were derived to convert renal uptake to clearance. Using one-sample clearance and integrated renal counts as dependent and independent variables, data were fitted to the models to determine the necessary constants. The correlations between the model estimated clearances and one-sample clearance were investigated., Results: One-sample clearance ranged from 11 to 404 ml x min(-1) per 1.73 m2. More than half of the regression using renal depth determined by the scatter fraction alone failed to converge. Among the successfully converged regressions, all model estimated clearances showed significant correlations (P<0.01) with one-sample clearance. The best correlation was observed in the model using renal depth determined by the combination of scatter fraction and Tønnesen's formulas, renal ROIs by 50% cut-off, lateral-inferior background and time interval of 2-3 min (r=0.898, P<0.001)., Conclusion: The renal uptake method for estimating the clearance of mercaptoacetyltriglycine can be improved by the processing conditions proposed here.