Interobserver agreement on captopril renography for assessing renal vascular disease.
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Captopril-stimulated renography is widely used to screen selected groups of hypertensive patients for renal vascular disease. Evaluation of the test is a complex task. Lack of interobserver agreement on the assessment and interpretation of renographic parameters may contribute to differences in sensitivity and specificity between studies. METHODS: Three experienced nuclear medicine physicians evaluated 658 renograms of 503 hypertensive patients suspected of having renal vascular disease from a large Dutch multicenter study (the Dutch Renal Artery Stenosis Intervention Cooperative [DRASTIC] study). Interobserver agreement on several renographic parameters was assessed by the kappa statistic and the intraclass correlation coefficient (ICC). RESULTS: The interobserver agreement on the time to excretion was high: The pooled ICC was 0.90. The pooled kappa was > or = 0.65 for the pattern of the time--activity curves, the visual aspect of the scintigraphic images (visible uptake and kidney size), and the judgment on the presence of renal artery stenosis. However, the interobserver agreement on cortical retention and pelvic retention by visual inspection of the images was rather low (pooled kappa = 0.46 and 0.52, respectively). Pelvic retention was found to complicate the interpretation of renography. CONCLUSION: Interobserver agreement on most of the renographic parameters was satisfactory, but the assessment of cortical retention was more difficult, in particular, in the presence of pelvic retention. Captopril renography should be interpreted with caution if pelvic retention is suspected. Interobserver variability offers one of several explanations for the differences in diagnostic test performance that are found between studies. (+info)
Tumor pretargeting in mice using (99m)Tc-labeled morpholino, a DNA analog.
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Over the past several years, investigators in this laboratory and elsewhere have been studying tumor localization by pretargeting with streptavidin and biotin or with avidin and biotin. Despite encouraging results, difficulties related to endogenous biotin and the immunogenicities of streptavidin and avidin have made a search for alternative strategies sensible. Recently, we have considered the use of DNAs and peptide nucleic acids for this purpose because oligomers can have hybridization affinities equivalent to that of biotin for streptavidin or avidin without the associated difficulties. We now report on the use of a morpholino (MORF), another commercially available synthetic oligomer, for pretargeting applications. MORFs support the nitrogenous bases by nonionic phosphorodiamidate linkages and, besides being nuclease resistant, can display good water solubility. METHODS: An 18mer MORF and its 18mer complementary MORF (cMORF) were obtained with a primary amine through a 3-member alkyl linker on the 3' equivalent end. An anti--carcinoembryonic antigen IgG antibody (MN14) was conjugated with MORF, whereas cMORF was conjugated with N-hydroxysuccinimide-mercaptoacetyltriglycine (MAG3) to permit radiolabeling with (99m)Tc. The biodistribution of labeled cMORF was first evaluated in normal CD-1 mice. Subsequently, nude mice bearing LS174T tumors received 50 microg conjugated antibody 48 h before the administration of 1.0 microg (7.4 MBq) (99m)Tc-MAG3-cMORF. Control animals received the labeled cMORF without prior administration of the antibody. A clearing step was not used. RESULTS: Biodistributions in normal mice showed that (99m)Tc-MAG3-cMORF was excreted rapidly through the kidneys, with only 7 percentage injected dose (%ID) remaining within the whole body (excluding urine) at 3 h. In tumor-bearing mice at 24 h, only 11 %ID of the radioactivity remained in the whole body of study animals, and of this amount, 2 %ID/g was in tumor tissue. The sites with the highest %ID were the kidneys, at 4 %ID/g, and the blood, at 0.5 %ID/g; all other organs had <1 %ID/g. At the same time, values for the control animals were 5 %ID (whole body), 0.05 %ID/g (tumor), and 3 %ID (kidneys). All images reflected high uptake in the tumors and low uptake in the normal tissues of the study mice. CONCLUSION: Pretargeting using MORFs was effective in a mouse tumor model. (+info)
Pitfalls of single-sample determination of renal clearance.
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BACKGROUND: Single-sample techniques are widely used for determination of renal clearance by elimination kinetics of radiolabelled marker substances. Frequently, however, formulae for transforming single-time measurement values into estimates of kinetic function, such as renal clearance, are being established exclusively by data reduction methods and are devoid of any physiological meaning. METHODS: Using 11 subjects with normal or impaired renal function, we compared one such method using (99m)Tc-labelled mercaptoacetyltriglycine ((99m)Tc-MAG(3)) for single-sample determination of tubular extraction rates with a more elaborate computer-based system identification technique. This latter method yields measures for glomerular filtration rate as well as effective renal plasma flow based on elimination kinetics of sinistrin and p-aminohippuric acid. RESULTS: When applying the single-sample technique, two of the 11 estimated values for tubular extraction rate were negative, indicating an erroneous analysis of kinetic behaviour. This single-sample method failure was not caused by the marker, but rather by the specific mathematical procedure used for the evaluation. Importantly, evaluation of the same experimental data with a conventional two-sample technique would eliminate the principal mathematical defect and produce physiologically reasonable results, without requiring additional effort. CONCLUSIONS: Our study does not criticize the (99m)Tc-MAG(3) technique per se. Rather, these findings indicate that usage of single-sample techniques for determination of inherently kinetic phenomena may produce incorrect results. Therefore, despite their obvious practical advantages, such simplified methods should be performed with great caution. (+info)
Factors affecting the hepatobiliary excretion of 99mTc-MAG3: its clinical significance in routine renography.
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OBJECTIVE: Since the approval of mercaptoacetyltriglycine (MAG3) for routine clinical use, reports have appeared about hepatobiliary excretion deleteriously affecting available diagnostic and quantitative information. The purpose of this study was to evaluate gallbladder (GB) uptake of MAG3 in the clinical setting and its effect on the evaluation of relative renal function and imaging. METHODS: Sixty patients with varying degrees of renal impairment were studied. Routine renal function imaging was followed with anterior and right lateral 3-min abdominal images. Factors such as photolytic degradation, reconstitution steps, (99m)Tc O(4) solution, age, and concentration are discussed. In addition, patient fasting state and radiochemical purity are evaluated. The GB uptake was determined as a percentage of the injected dose. RESULTS: The MAG3 quality control ranged from 90.9% to 99.0%. The GB uptake ranged from 0.0% (not visualized) to 0.71%. The effective renal plasma flow ranged from 88 to 743 mL/min. There was no correlation between the QC and the percentage of GB uptake (r = 0.12). The majority of patients in the nonfasting state showed minimal or reduced GB uptake when compared with the majority of patients in the fasting state. CONCLUSION: Our data suggest that GB uptake of MAG3 is minimal, with no adverse effects on the diagnostic and quantitative analysis of renal function. (+info)
Value of supranormal function and renogram patterns on 99mTc-mercaptoacetyltriglycine scintigraphy in relation to the extent of hydronephrosis for predicting ureteropelvic junction obstruction in the newborn.
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We investigated the value of supranormal function and renogram patterns on (99m)Tc-mercaptoacetyltriglycine ((99m)Tc-MAG3) scintigraphy in relation to the extent of hydronephrosis for predicting ureteropelvic junction (UPJ) obstruction in the newborn. METHODS: We studied 48 patients with prenatally diagnosed unilateral hydronephrosis that was confirmed on postnatal ultrasonography. The anteroposterior pelvic diameter (APPD) and the Society for Fetal Urology (SFU) grade were measured on 1-mo ultrasonography to assess the extent of hydronephrosis. Neonates with an APPD of or=55%) and renogram grades (1, not obstructive; 2, indeterminate; 3, obstructive; and 4, prolonged parenchymal transit) were determined on 1-mo (99m)Tc-MAG3 renography. Multivariate logistic regression analysis was performed to predict the presence of obstruction. RESULTS: Of the 48 kidneys with hydronephrosis, 19 were diagnosed as having UPJ obstruction. Twenty-nine kidneys were classified as having nonobstructive hydronephrosis. The APPD of the 19 kidneys with obstruction (24.3 +/- 9.2 mm) was significantly larger than that of the 29 kidneys without obstruction (17.5 +/- 11.2 mm; P < 0.05). The SFU grades of UPJ obstruction (2 with grade 3, 17 with grade 4) were also significantly higher than those without UPJ obstruction (grades 1-4 in 1, 6, 10, and 12 kidneys, respectively; P < 0.01). Supranormal function was present in 4 kidneys with UPJ obstruction but in none without obstruction (P < 0.001). (99m)Tc-MAG3 renography of the 19 obstructions showed grades 2, 3, and 4 renograms in 4, 8, and 7 patients, respectively. The 29 without obstruction revealed significantly lower grades (grades 1-4 in 10, 13, 5, and 1 patient, respectively; P < 0.001). Multivariate logistic regression analysis revealed that the addition of supranormal function or renogram grade in the model significantly increased the likelihood ratio in comparison with that of the SFU grade only (chi(2) = 7.73 and 9.99, respectively; P < 0.01). Of the 29 neonates with SFU grade 4, supranormal function or renogram >or= grade 4 had a positive predictive value of 90% (9/10). CONCLUSION: (99m)Tc-MAG3 renography at 1 mo after birth has a significant additive value in relation to the degree of hydronephrosis in predicting UPJ obstruction in patients with prenatally diagnosed unilateral hydronephrosis with normal function. (+info)
Testing different storage conditions for (99m)Tc-MAG3 kit: can hot fractioning reduce the cost per unit dose?
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Since its release for routine clinical use, (99m)Tc-mercaptoacetyltriglycine (MAG3) has become an important alternative to (131)I-labeled orthoiodohippuran. The cold kit for MAG3 is expensive, especially in developing countries. Therefore, unique storage conditions should be provided for cost reduction. Cold fractioning is a well-known procedure but has special requirements, such as a nitrogen tank and a laminar flow hood. The aim of this study was to prolong the shelf life of (99m)Tc-labeled MAG3 by a hot fractioning method, which separates the patient doses after (99m)Tc labeling. The radiochemical purity of the (99m)Tc-labeled MAG3 kit was tested under different storage conditions. Hot fractioning of the (99m)Tc-labeled MAG3 kit was found to be a possible alternative to cold fractioning for routine clinical studies. (+info)
A Bayesian 3-compartment model for 99mTc-MAG3 clearance.
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Because recent reports have questioned the traditional 2-compartment model for calculating tracer clearance after a single intravenous injection, a 3-compartment model was evaluated in this study. METHODS: Bayesian statistics were used, which facilitated curve fitting by treating all subjects simultaneously. (99m)Tc-Mercaptoacetyltriglycine clearance data from 154 adults and 109 children were measured at several centers, typically 6-9 plasma samples spanning 5-90 min, and fitted by 2- and 3-compartment Bayesian models. RESULTS: Clearance estimates were found to be systematically lower for the 3-compartment model than for the 2-compartment model. A single-sample procedure based on the 3-compartment model was found to eliminate most of the known discrepancy between formulas based on single-injection and continuous-infusion reference methods. CONCLUSION: A 3-compartment model led to lower and probably more accurate clearance estimates than the conventional 2-compartment model. A new single-sample method is presented, based on the 3-compartment model as reference standard. (+info)
Can technetium-99m-mercaptoacetyltriglycine replace technetium-99m-dimercaptosuccinic acid in the exclusion of a focal renal defect?
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The presence of focal renal damage dictates different management of a child with urinary tract infection (UTI) compared with children who have normal kidneys. Technetium-99m-dimercaptosuccinic (DMSA) has a high sensitivity in the detection of a focal defect, and allows estimation of differential function. The introduction of 99mTc-MAG3 with high renal extraction suggests that this may be useful in children with UTI but its role remains speculative. Fifty-nine children with previous UTI underwent both 99mTc-DMSA and MAG3 within 4 wk of each other. Differential function and assessment of the images were undertaken. There is close correlation (R2 = 0.97) between the differential function. Analysis of the 99mTc-DMSA and functional MAG3 images showed that the functional image had a specificity of 88% and a sensitivity of 88% in the detection of a focal parenchymal defect. Technetium-99m-MAG3 in the clinical setting of a child with UTl allows accurate assessment of differential function and a high probability of detecting a focal renal abnormality. (+info)