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Purpose: To precisely quantify split glomerular filtration rate by Tc-99m-DTPA renal dynamic imaging and plasma clearance in order to increase its consistency among doctors., Methods: Tc-99m-DTPA renal dynamic imaging was performed according to the conventional radionuclide renal dynamic imaging by five double-blinded doctors independently and automatically calculated split GFR, namely, gGFR. Moreover, the conventional radionuclide renal dynamic imaging was assessed to only outline the kidney, blank background, and automatically calculated split GFR, gGFR'. The total GFR value of patients, tGFR, was obtained by the double-plasma method. According to the formula, Precise GFR (pGFR) = gGFR'/(gGFR' + gGFR') × tGFR. The precise GFR value of the divided kidney, pGFR, was calculated. The Kendall's W test was used to compare the consistency of gGFR and pGFR drawn by five physicians., Results: According to Kendall's W consistency test, Kendall's coefficient of concordance was 0.834, p = 0.0001 using conventional method. The same five doctors used blank background again and the same standard Gates method to draw the kidneys, which automatically calculated gGFR'. Using input formula, the pGFR was calculated and Kendall's W consistency test (Kendall's coefficient of concordance = 0.956, p = 0.0001)., Conclusion: The combination of Tc-99m-DTPA renal dynamic imaging combined with the double-plasma method could achieve accurate split GFR, and because of the omission of influence factors, the consistency of pGFR obtained by different doctors using this method was significantly higher than that of conventional Tc-99m-DTPA renal dynamic imaging., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Xiaoxi Pang et al.)

Measurement of glomerular filtration rate (GFR) from the plasma clearance of a radionuclide-labeled tracer is reliable and accurate. However, to avoid contamination of the blood samples with radioactivity remaining at the injection site, venepuncture at 2 or more sites is required: one for tracer administration and the others for blood sampling. This requirement is uncomfortable for patients, particularly when venous access is difficult. The objective of this study was to validate the use of a single site of venous access in combination with injection site imaging, for GFR measurement. Methods: Twenty-two adults (≥18 y) who were referred for GFR determination were included prospectively. GFR was measured from the plasma clearance of 99m Tc-diethylenetriaminepentaacetic acid according to international guidelines. After administration of the tracer through an intravenous cannula, a 60-s static image of the injection site was acquired. A second intravenous cannula was inserted into the contralateral arm. Venous blood samples were collected at 2, 3, and 4 h after administration of the radiotracer from both the injection site (experimental) and the contralateral arm (conventional). GFR was calculated using slope-intercept and single-sample methods. The median conventional and experimental plasma counts (decay- and background-corrected) were compared for the 2-, 3-, and 4-h venous samples. Conventional and experimental GFRs were then compared, with a more than 10% difference between conventional and experimental GFRs being regarded as significant. Results: Four individuals had visible residual activity at the injection site. The median 2-h counts differed significantly between the conventional and experimental sampling sites ( P = 0.007), whereas no significant difference was found at 3 or 4 h. When there was a clear injection site image, the difference between the experimental and conventional GFRs was more than 10% in 1 case for single-sample GFR but less than 8% in all cases for slope-intercept GFR. Conclusion: In cases with clear injection site images, slope-intercept GFR calculated after injection site blood sampling showed no clinically significant difference from conventional contralateral-arm sampling., (© 2019 by the Society of Nuclear Medicine and Molecular Imaging.)

Both 99m Tc-DTPA and 51 Cr-EDTA are widely used to determine glomerular filtration rate (GFR), but few direct comparative studies exist. The shortage of 51 Cr-EDTA makes a direct comparison highly relevant. The aim of the study was to investigate if there is any clinically relevant difference between plasma clearance of 99m Tc-DTPA and 51 Cr-EDTA. Patients ≥18 years of age referred for routine GFR measurement by 51 Cr-EDTA were prospectively enrolled. The two tracers (10 MBq 99m Tc-DTPA (CaNa 3 -DTPA) and 2.5 MBq 51 Cr-EDTA) were intravenously injected at time zero. A standard 4-sample technique was applied with samples collected at 180, 200, 220 and 240 min, if the estimated GFR (eGFR) was ≥30 mL/min. A comparison of single-sample GFR based on the 200 min sample was also conducted. Fifty-six patients were enrolled in the study. All patients had an estimated GFR >30 mL/min/1.73 m 2 . No patients suffered from ascites or significant oedema. The mean 51 Cr-EDTA plasma clearance was 82 mL/min (range 16-226). The plasma clearances determined by the two methods were highly correlated ( r  = 0.993). The plasma clearance was significantly higher when measured by 99m Tc-DTPA than by 51 Cr-EDTA ( p  = 0.01), but the numerical difference was minimal (mean difference 1.4 mL/min; 95% limits of agreement (LOA) -6.6 to 9.4). The difference between the two methods was independent of the level of renal function. Similar results were found for one-sample GFR. No clinically relevant differences were found between the plasma clearance of 99m Tc-DTPA and that of 51 Cr-EDTA. Therefore, 99m Tc-DTPA can replace 51 Cr-EDTA when needed.

Objective: To evaluate agreement of 4 methods (Tikhonov gamma variate adaptive regularization of plasma concentration-time curve fitting applied to technetium Tc 99m diethylenetriamine pentaacetic acid [ 99m Tc-DTPA] plasma clearance [Tk-GV], plasma clearance of exogenous creatinine [CrCL], Gates gamma camera-based measurement method with 99m Tc-DTPA renal clearance and dynamic scintigraphy [GTS], and iohexol renal clearance assessed with dynamic CT with Patlak plotting [CT-Pp]) for measuring glomerular filtration rates (GFR) in healthy cats., Animals: 7 healthy, laboratory-raised cats., Procedures: Each method for measuring GFR was performed twice in 7 cats at 24-day intervals. The Wilcoxon signed-rank sum test was used to compare the results obtained from the 14 studies for each method. Results from the 4 methods were assessed for agreement and correlation., Results: The median GFR values were 2.75, 2.83, 3.14, and 4.26 mL/min/kg, for Tk-GV, CT-Pp, plasma CrCL, and GTS, respectively. Analysis with Wilcoxon signed-rank sum tests identified significant pairwise differences between results obtained with the Tk-GV versus the plasma CrCL method, the Tk-GV versus the GTS method, and the plasma CrCL versus the GTS method. The least variable method was Tk-GV, with an SD of 1.27 (mL/min/kg)., Conclusions and Clinical Relevance: Findings indicated that Tk-GV yielded GFR measurements comparable with those obtained with CT-Pp, plasma CrCL, and GTS; however, the Tk-GV method yielded the tightest range of results among the methods evaluated.

Background: Measurements of GFR may be performed with a slope/intercept method (S/I), using only two blood samples taken in strictly defined time points. The aim of the study was to modify this method in order to extend time intervals suitable for blood sampling. Modification was based on a variation of a Russel et al. model parameter, selection of time intervals suitable for blood sampling and assessment of uncertainty of calculated results., Material and Methods: Archived values of GFR measurements of 169 patients with different renal function, from 5.5 to 179 mL/min, calculated with a multiple blood sample method were used. Concentrations of a radiopharmaceutical in consecutive minutes, from 60th to 190th after injection, were calculated theoretically, using archived parameters of biexponential functions describing a decrease in 99mTc-DTPA concentration in blood plasma with time. These values, together with injected activities, were treated as measurements and used for S/I clearance calculations. Next, values of S/I clearance were compared with the multiple blood sample method in order to calculate suitable values of exponent present in a Russel's model, for every combination of two blood sampling time points. A model was considered accurately fitted to measured values when SEE ≤ 3.6 mL/min. Assessments of uncertainty of obtained results were based on law of error superposition, taking into account mean square prediction error and also errors introduced by pipetting, time measurement and stochastic radioactive decay., Results: The accepted criteria resulted in extension of time intervals suitable for blood sampling to: between 60 and 90 minutes after injection for the first sample and between 150 and 180 minutes for the second sample. Uncertainty of results was assessed as between 4 mL/min for GFR = 5-10 mL/min and 8 mL/min for GFR = 180 mL/min., Conclusions: Time intervals accepted for blood sampling fully satisfy nuclear medicine staff and ensure proper determination of GFR. Uncertainty of results is entirely acceptable and for high GFR values even comparable with uncertainty of multi-sample measurements.

Glomerular filtration rate (GFR) measurements are critical in patients with hepatic cirrhosis but potentially erroneous when based on serum creatinine. New equations for estimated GFR (eGFR) have shown variable performance in cirrhotics, possibly because of inaccuracies in reference methods for measured GFR (mGFR). The primary objective was to compare the performance of 4 improved eGFR equations with a 1-compartment, 2-sample plasma slope intercept 99m Tc-DTPA mGFR method to determine whether any of the eGFR calculations could replace plasma 99m Tc-DTPA mGFR in patients with cirrhosis. The secondary objective was to test the hypothesis that mGFR using voluntary voided urine collections introduces error compared with plasma-only methods. Methods: Fifty-four patients with hepatic cirrhosis underwent mGFR determinations from 2 plasma samples at 1 and 3 h after intravenous administration of 185 MBq of 99m Tc-DTPA. GFR was also generated by a UV/P calculation derived from blood and urine samples. These mGFRs were compared with the eGFRs generated by 4 estimating equations: MDRD (Modified Diet in Renal Disease), CKD-EPI (Chronic Kidney Disease-Epidemiology Collaboration) (serum creatinine [SCr]), CKD-EPI (cystatin [CysC]), and CKD-EPI (CysC+SCr). eGFRs were compared with mGFRs by Pearson correlation, precision, bias, percentage bias, and accuracy (eGFRs varying by <10% [p10], <20% [p20] or <30% [p30] from the corresponding mGFR). Results: All eGFRs showed poorer performance when the UV/P 99m Tc-DTPA mGFR was used as the reference than when the plasma 99m Tc-DTPA mGFR was used. When compared with the plasma 99m Tc-DTPA mGFR method, the performance of all eGFR equations was superior to most published reports. There was a moderately good positive correlation between eGFRs and mGFRs. When compared with plasma 99m Tc-DTPA mGFR, precision of eGFRs was in the range of 14-20 mL/min and showed a negligible bias. Compared with the plasma 99m Tc-DTPA mGFR, CKD-EPI (CysC+SCr) showed the best overall performance and accuracy, at 85.19% (p30), 75.93% (p20), and 42.59% (p10). Conclusion: Estimating equations for measuring eGFR performed better than in most published reports, attributable to use of the plasma 99m Tc-DTPA mGFR method as a reference. CKD-EPI (CysC+SCr) eGFR showed the best overall performance. However, more discriminating methods may be required when accurate GFR measurements are necessary. mGFR measurements using urine collections may introduce error compared with plasma-only methods., (© 2017 by the Society of Nuclear Medicine and Molecular Imaging.)

Measuring glomerular filtration rate (GFR) by dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) as part of standard of care clinicalMRIexams (e.g., in pediatric solid tumor patients) has the potential to reduce diagnostic burden. However, enthusiasm for this relatively newGFRtest may be curbed by the limited amount of cross-calibration studies with referenceGFRtechniques and the vast variety ofMRtracer model algorithms causing confusion on the choice of model. To advanceMRI-basedGFRquantification via improvedGFRmodeling and comparison with associated(99m)Tc-DTPA-GFR, 29 long-term Wilms' tumor survivors (19.0-43.3 years, [median 32.0 ± 6.0 years]) treated with nephrectomy, nonnephrotoxic chemotherapy ± radiotherapy underwentMRIwith Gd-DTPAadministration and a(99m)Tc-DTPA GFRtest. ForDCE-MRI-basedGFRestimation, a subject-specific two-compartment (SS-2C) model was developed that uses individual hematocrit values, automatically defines subject-specific uptake intervals, and fits tracer-uptake curves by incorporating these measures. The association between reference(99m)Tc-DTPA GFRandMR-GFRs obtained bySS-2C, three published 2C uptake, and inflow-outflow models was investigated via linear regression analysis. Uptake intervals varied from 64 sec to 141 sec [96 sec ± 21 sec] and hematocrit values ranged from 30% to 49% [41% ± 4%]; these parameters can therefore not be assumed as constants in 2C modeling. OurMR-GFRestimates using theSS-2C model showed accordingly the highest correlation with(99m)Tc-DTPA-GFRs (R(2) = 0.76,P < 0.001) compared with other models (R(2)-range: 0.36-0.66). In conclusion,SS-2C modeling ofDCE-MRIdata improved the association betweenGFRobtained by(99m)Tc-DTPAand Gd-DTPA DCE-MRIto such a degree that this approach could turn into a viable, diagnosticGFRassay without radiation exposure to the patient., (© 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.)

Objectives: Glomerular filtration rate can be measured as the plasma clearance (CL) of a glomerular filtration rate marker despite body fluid disturbances using numerous, prolonged time samples. We desire a simplified technique without compromised accuracy and precision., Materials and Methods: We compared CL values derived from two plasma concentration curve area methods - (a) biexponential fitting [CL (E2)] and (b) Tikhonov adaptively regularized gamma variate fitting [CL (Tk-GV)] - for 4 versus 8 h time samplings from 412 Tc-DTPA studies in 142 patients, mostly paediatric patients, with suspected fluid disturbances., Results: CL (Tk-GV) from four samples/4 h and from nine samples/8 h, both accurately and precisely agreed with the standard, which was taken to be nine samples/8 h CL from (noncompartmental) numerical integration [CL (NI)]. The E2 method, four samples/4 h, and nine samples/8 h median CL values significantly overestimated the CL (NI) values by 4.9 and 3.8%, respectively., Conclusion: Compared with the standard, CL (E2) from four samples/4 h and from nine samples/8 h proved to be the most inaccurate and imprecise method examined, and can be replaced by better methods for calculating CL. The CL (Tk-GV) can be used to reduce sampling time in half from 8 to 4 h and from nine to four samples for a precise and accurate, yet more easily tolerated and simplified test.

Aims: To assess the performance of the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation at baseline and longitudinally in people with type 2 diabetes., Methods: Adults with type 2 diabetes attending Austin Health, Melbourne, with≥3 prospective GFR measurements were included in this retrospective study. Plasma disappearance rate of DTPA (diethylene-triamine-penta-acetic acid) was used to calculate measured GFR (mGFR) and compared to estimated GFR (eGFR). The agreement between mGFR and eGFR was estimated using Intraclass Correlation Coefficient (ICC)., Results: 152 patients had a median of 4 (IQR: 3, 5) mGFR measurements over a period of 11years (IQR: 9, 12). The difference between mGFR and eGFR increased proportionally to the magnitude of the GFR, increasing by 0.2ml/min/1.73m(2) for every 1ml/min/1.73m(2) increase in mGFR, indicative of proportional bias. At lower mGFR levels, eGFR overestimated mGFR, and at higher mGFR levels, eGFR underestimated mGFR. There was a significant association between LDL cholesterol, triglycerides, HbA1c, diastolic blood pressure and the difference between mGFR and eGFR., Conclusions: The CKD-EPI formula underestimates mGFR and the rate of decline of mGFR in patients with type 2 diabetes with an mGFR greater than 60ml/min/1.73m(2). The association between LDL cholesterol, triglycerides, HbA1c, diastolic blood pressure and the difference between mGFR and eGFR warrants further study., (Copyright © 2016. Published by Elsevier Inc.)

Unlabelled: Glomerular filtration rate (GFR) is the best indicator of renal function. The gold standard for GFR measurement is inulin clearance. However, its measurement is inconvenient, time-consuming, and costly. Thus, in both scientific studies and routine clinical practice nuclear medicine methods ((99m)Tc-diethylenetriaminepentaacetic acid [(99m)Tc-DTPA] and (51)Cr-ethylenediaminetetraacetic acid [(51)Cr-EDTA]) are preferred, and they correlate strongly with inulin clearance. In addition, cystatin C and β-trace protein have also recently been used for this purpose. In the literature, however, data are limited about the clinical value of cystatin C and β-trace protein in GFR measurement in chronic renal disease (CRD), and the results have been inconclusive. In this study, we aimed to determine the efficiency of cystatin C and β-trace protein in the determination of GFR in CRD patients., Methods: Eighty-four patients with CRD were included in the study (59 men and 25 women; age range, 21-88 y; mean age, 61 y). GFR was calculated using the gold-standard (99m)Tc-DTPA 2-sample plasma sampling method (TPSM) and 2 alternative methods: a formula using cystatin C and a formula using β-trace protein. The correlation between TPSM and the cystatin C and β-trace protein methods was assessed, and Bland-Altman analysis was used to graph scatterplots of the differences at a confidence interval of 95% (mean difference ± 1.96 SDs)., Results: GFRs calculated using both alternative methods correlated strongly with those calculated using the gold standard. However, the correlation was stronger for the cystatin C method than for the β-trace protein method, and neither method produced reliably consistent GFRs., Conclusion: This study demonstrated that cystatin C and β-trace protein do not reflect GFR with sufficient accuracy., (© 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Objective: Glomerular filtration rate (GFR) is frequently assessed using the slope-intercept method by fitting a single exponential to plasma samples obtained 2-5 h after injection. The body surface area (BSA)-corrected one-pool clearance (CO,BSA) overestimates true GFR (CT,BSA) because it fails to sample the full plasma curve, and values of CT,BSA are usually estimated from CO,BSA using the Brøchner-Mortensen (BM) equation. An improved equation, CT,BSA=CO,BSA/(1+fBSA×CO,BSA), with fBSA a fixed constant, was proposed by Fleming, but subsequently Jødal and Brøchner-Mortensen (JBM) reported that fBSA varies with BSA. We report data for a large group of individuals who underwent GFR investigations with sampling of the full plasma curve. The aims were to validate the JBM equation with independent data and assess whether replacing the BM equation with a BSA-dependent correction based on Fleming's equation can increase the accuracy of the slope-intercept method., Methods: Plasma data were analysed for 142 children and adults aged 0.6-56 years who underwent technetium-99m-diethylenetriaminepentaacetic acid GFR investigations with blood samples taken between 5 min and 8 h after injection. Values of CO,BSA were calculated using the 2, 3 and 4 h data. Values of CT,BSA were calculated by integrating the plasma curve between 5 min and 4 h and extrapolating the terminal exponential. Individual values of fBSA were calculated using the relationship fBSA=1/CT,BSA-1/CO,BSA. Nonlinear regression was used to fit the function fBSA=f1×BSA and find the best-fit values for f1 and n. Scatter and Bland-Altman plots were drawn comparing the various formulae for correcting slope-intercept GFR., Results: The trend for fBSA to decrease with increasing BSA was highly significant (Spearman's test: RS=-0.31; P=0.0002). When the data were fitted by nonlinear regression, the best-fit values (95% confidence interval) of the model parameters were n=-0.13 (from -0.21 to -0.04) and f1=0.00191 (from 0.00183 to 0.00200)., Conclusion: The results confirm that fBSA varies with BSA and provide independent values of the parameters f1 and n. Differences from GFRs calculated using the original JBM equation were small and not clinically significant. The BM equation also performed well for CT,BSA less than 125 ml/min/1.73 m. However, there was a small number of children with CT,BSA greater than 150 ml/min/1.73 m for whom the JBM formula provided more accurate estimates of true GFR than did the BM equation.

Aim: The aim of this study was to investigate the value of cystatin C and beta-trace protein (BTP) levels in determination of the glomerular filtration rate (GFR) by accepting the technetium-99m diethylenetriamine pentaacetic acid (Tc-DTPA) method as the gold standard for GFR measurement in renal transplant patients with stable renal functions and to investigate the value of cystatin C and BTP levels in the determination of GFR in cases with or without renal tubular injury., Methods: A total of 89 (60 men and 29 women) renal transplant patients aged 19-67 years (mean 38.15 years) with stable graft functions were included in the study. GFR was calculated using three different methods: (a) the Tc-DTPA two plasma sample method; (b) eight different formulas containing cystatin C; and (c) three different formulas containing BTP. In addition, the cases were divided into two groups on the basis of N-acetyl-β-D-glucosaminidase and β2 microglobulin levels showing tubular damage., Results: GFR values obtained with cystatin C had a better correlation with the gold standard method compared with those obtained with BTP, and the GFR value obtained with cystatin C had the most reliable consistency. We found that cystatin C provided more accurate results in GFR follow-up in renal transplant patients with no tubular injury compared with those with tubular injury., Conclusion: Cystatin C is a good marker of GFR in renal transplant patients, especially in those with no tubular injury; however, BTP is not as good as cystatin C in that regard.

The radiopharmaceutical (99m)Tc-DTPA (diethylene-triamine-pentaacetic acid) is a tracer widely used in renal scintigraphy to assess glomerular filtration rate. The estimation of protein binding is very important due to its impact on clinical parameters biodistribution since only the free fraction is filtered by the kidney. A number of laboratory techniques have been developed to study protein binding. Precipitation and ultrafiltration are the mostly used techniques in pharmacology for studies of the binding between proteins and small molecules. The aim of this work is to apply and compare those two analytical methods in (99m)Tc-DTPA protein binding determination in vitro before in vivo application. The results obtained by precipitation with trichloroacetic acid are not enough reproducible, while those obtained by ultrafiltration seem more consistent and reproducible., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Background and Aim: Assessment of volume of distribution (VD) and half-life (T1/2) values during glomerular filtration rate (GFR) investigations is a useful quality control check. The aim of this study was to derive reference data for VD and T1/2 and also to provide reference data for GFR from studies performed using Tc-diethylenetriaminepentaacetic acid (Tc-DTPA)., Methods: This was a retrospective study of 126 healthy potential kidney donors (age range 18-59 years). The GFR was evaluated from Tc-DTPA plasma clearance using the 2004 British Nuclear Medicine Society guidelines. The association between VD and body surface area (BSA) was assessed. T1/2 was correlated with age and GFR. The correlation between the Brochner-Mortensen-corrected GFR (BM-GFRCorr) and age was evaluated., Results: The uncorrected VD value (l) was 10.1×BSA±40.6% (P<0.01). The corrected VD value (l) was 8.19×BSA±34.4% (P<0.01). In individuals under the age of 40 years, the mean T1/2 was 95.0 min±36.2%. In individuals aged 40 years and above, the T1/2 increased at a rate of 0.49 min/year (P=0.04); the T1/2 (min) was 9480×(1/BM-GFRCorr)±35.1% (P<0.01). In individuals younger than 40 years of age, the correlation between BM-GFRCorr and age was not statistically significant (P=0.45), and the mean GFR was 108 ml/min/1.73 m±27.5%. In individuals aged 40 years and above, the BM-GFRCorr was 170-(1.55×age) ml/min/1.73 m±36.7% (P<0.001)., Conclusion: Well-defined reference data for VD and T1/2 can be used for quality control checks in GFR investigations. In addition to these, reference data for GFR using Tc-DTPA have been defined. This will enhance the interpretation of adult Tc-DTPA GFR measurements.

Background: To investigate the impact of serum creatinine measurement on the applicability of glomerular filtration rate (GFR) evaluation equations., Methods: 99mTc-DTPA plasma clearance rate was used as GFR reference (rGFR) in patients with chronic kidney disease (CKD). Serum creatinine was measureded using enzymatic or picric acid creatinine reagent. The GFR of the patients were estimated using the Cockcroft-Gault equation corrected for body surface area, simplified Modification of Diet in Renal Disease (MDRD) equation, simplified MDRD equation corrected to isotopes dilution mass spectrometry, the CKD epidemiology collaborative research equation, and two Chinese simplified MDRD equations., Results: Significant differences in the eGFR results estimated through enzymatic and picric acid methods were observed for the same evaluation equation. The intraclass correlation coefficient (ICC) of eGFR when the creatinine was measured by the picric acid method was significantly lower than that of the enzymatic method. The assessment accuracy of every equation using the enzymatic method to measure creatinine was significantly higher than that measured by the picric acid method when rGFR was > or = 60 mL/min/1.73m2., Conclusions: A significant difference was demonstrated in the same GFR evaluation equation using the picric acid and enzymatic methods. The enzymatic creatinine method was better than the picric acid method.

Objective: The aim of this study is to assess the comparability and interchangeability of the radionuclide glomerular filtration rate (GFR) using different published techniques, and propose normative data for paediatrics., Methods: A total of 476 paediatric oncology patients aged 2-17 years, referred between January 2001 and December 2008 for GFR estimation, were reviewed for any potential cause of renal impairment. Sixty-nine patients met the stringent inclusion criteria, and were included in the study. GFR estimation was carried out using either technetium-99m diethylene triamine penta-acetic acid (⁹⁹mTc-DTPA) or chromium-51 EDTA (⁵¹Cr-EDTA). Multiple GFR results were calculated from the same blood sample data (counts/min/ml), according to previously published GFR estimation techniques using one to three blood samples. These techniques were slope-intercept, slope-only and half life. For slope-intercept techniques, GFR was normalized to body surface area or extracellular fluid volume., Results: The GFR values obtained using different techniques were highly variant. The intraclass correlation (ICC) for different methods was moderate (ICC=0.56-0.66). A reliable empiric formula to allow conversion of GFR values from one technique to another could not be derived because of this variability, with some exceptions. ⁵¹Cr-EDTA yielded the same or lower variability than ⁹⁹mTc-DTPA. The British Nuclear Medicine Society-recommended method had the lowest coefficient of variation, with a mean value of 116 (SD 22) normalized to 1.73 m² for ⁵¹Cr-EDTA using two samples., Conclusion: The GFR values obtained from different calculation techniques are not readily interchangeable or comparable, with some exceptions. For both ⁹⁹mTc-DTPA and ⁵¹Cr-EDTA, the British Nuclear Medicine Society-recommended technique appears to be the most robust, with the least coefficient of variation.

The archaeolipids (lipids extracted from archaebacterias) are non saponificable molecules that form self sealed mono or bilayers (archaeosomes-ARC). Different to liposomes with bilayers made of conventional glycerophospholipids, the bilayer of ARC posses a higher structural resistance to physico chemical and enzymatic degradation and surface hydrophobicity. In this work we have compared the binding capacity of ARC exclusively made of archaeols containing a minor fraction of sulphoglycophospholipids, with that of liposomes in gel phase on M-like cells in vitro. The biodistribution of the radiopharmaceutical (99m)Tc-DTPA loaded in ARC vs that of liposomes upon oral administration to Wistar rats was also determined. The fluorescence of M-like cells upon 1 and 2h incubation with ARC loaded with the hydrophobic dye Rhodamine-PE (Rh-PE) and the hydrophilic dye pyranine (HPTS) dissolved in the aqueous space, was 4 folds higher than upon incubation with equally labeled liposomes. Besides, 15% of Rh-PE and 13 % of HPTS from ARC and not from liposomes, were found in the bottom wells, a place that is equivalent to the basolateral pocket from M cells. This fact suggested the occurrence of transcytosis of ARC. Finally, 4 h upon oral administration, ARC were responsible for the 22.3 % (3.5 folds higher than liposomes) shuttling of (99m)Tc-DTPA to the blood circulation. This important amount of radioactive marker in blood could be a consequence of an extensive uptake of ARC by M cells in vivo, probably favored by their surface hydrophobicity. Taken together, these results suggested that ARC, proven their adjuvant capacity when administered by parenteral route and high biocompatibility, could be a suitable new type of nanoparticulate material that could be used as adjuvants by the oral route.

Effects of sucralose sweetener on blood constituents labelled with technetium-99m ((99m)Tc) on red blood cell (RBC) morphology, sodium pertechnetate (Na(99m)TcO(4)) and diethylenetriaminepentaacetic acid labeled with (99m)Tc ((99m)Tc-DTPA) biodistribution in rats were evaluated. Radiolabeling on blood constituents from Wistar rats was undertaken for determining the activity percentage (%ATI) on blood constituents. RBC morphology was also evaluated. Na(99m)TcO(4) and (99m)Tc-DTPA biodistribution was used to determine %ATI/g in organs. There was no alteration on RBC blood constituents and morphology %ATI. Sucralose sweetener was capable of altering %ATI/g of the radiopharmaceuticals in different organs. These findings are associated to the sucralose sweetener in specific organs., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

The Tk-GV model fits Gamma Variates (GV) to data by Tikhonov regularization (Tk) with shrinkage constant, λ, chosen to minimize the relative error in plasma clearance, CL (ml/min). Using (169)Yb-DTPA and (99m)Tc-DTPA (n = 46, 8-9 samples, 5-240 min) bolus-dilution curves, results were obtained for fit methods: (1) Ordinary Least Squares (OLS) one and two exponential term (E₁ and E₂), (2) OLS-GV and (3) Tk-GV. Four tests examined the fit results for: (1) physicality of ranges of model parameters, (2) effects on parameter values when different data subsets are fit, (3) characterization of residuals, and (4) extrapolative error and agreement with published correction factors. Test 1 showed physical Tk-GV results, where OLS-GV fits sometimes-produced nonphysical CL. Test 2 showed the Tk-GV model produced good results with 4 or more samples drawn between 10 and 240 min. Test 3 showed that E₁ and E₂ failed goodness-of-fit testing whereas GV fits for t > 20 min were acceptably good. Test 4 showed CL(Tk-GV) clearance values agreed with published CL corrections with the general result that CL(E1) > CL(E2) > CL(Tk-GV) and finally that CL(Tk-GV) were considerably more robust, precise and accurate than CL(E2), and should replace the use of CL(E2) for these renal markers.

Objective: It was assessed whether cystatin C (cysC) could be used as a marker of glomerular filtration rate (GFR) by considering the technetium-99m diethylenetriamine penta-acetate (Tc-99m DTPA)-two blood sample method (GFRTc-99m DTPA) as the reference in pediatric patients under chemotherapeutic treatment., Methods: The chemotherapy group (CG) consisted of 31 patients (21 females, 10 males median age: 8.2 years; range: 2-16 years) who had been planned to receive allogenic hematopoietic stem cell transplantation. All patients in the CG received conditioning regimen (includes chemotherapy protocol) before hematopoietic stem cell transplantation. In addition, 21 patients (14 females, seven males median age: 9.5 years; range: 4-16 years) without any chemotherapy (nonchemotherapy group: nCG) were also prospectively investigated. Serum cysC, serum creatinine, GFRTc-99m DTPA, and GFR with a cysC-based formula (GFRcysC) were analyzed. Tubular function was also assessed., Results: Although we found good correlation between GFRTc-99m DTPA and cysC (r = -0.78), GFRTc-99m DTPA and GFRcysC (r = 0.91), cysC and creatinine (r = 0.91) in nCG, the same correlations were poor in CG (r = -0.42, r = 0.43, r = 0.46, respectively). Tubular function was impaired after chemotherapy. Bias+/-1.96 SD values were -6+/-15.7 and -3+/-54.8 ml/min/1.73 m in nCG and CG, respectively. Precision was also better in nCG (10 ml/min/1.73 m) than in CG (27.6 ml/min/1.73 m)., Conclusion: Serum cysC and GFRcysC cannot reflect GFR accurately in pediatric patients under chemotherapeutic treatment. Tubular cell damage induced by chemotherapeutics could be a responsible factor through the impairment of tubular absorption and metabolism of cysC.

Objective: To assess early nephrotoxicity of CDDP (Cis-diamminedichloroplatinum) manifested by a decline in the glomerular filtration rate (GFR) estimated by plasma two sample clearance method (PSC 2) after 99mTc-DTPA injection., Study Design: Descriptive study., Place and Duration of Study: Department of Nuclear Medicine, Karachi Institute of Radiotherapy and Nuclear Medicine, Karachi, from September 2004 to January 2005., Methodology: The renal function was assessed on 36 patients suffering from different types of cancer and receiving CDDP in doses of (3) 50 mg/m(2) before and after in each of six CDDP cycles. The GFR was determined by PSC 2 method after 99mTc-DTPA injection). A paired sample t-test was used for comparison of the mean value with significance at p < 0.01., Results: There were (28 males and 8 females; age range being 16-68 years) The average decline in GFR baseline to the end of sixth cycles was 43.86 ml/min/1.73m(2) (p=0.000) as estimated by PSC 2 method. There was a significant fall of average 9.36 ml/min/1.73m(2) (p < 0.01) in GFR as observed in each cycle of CDDP estimated by the PSC 2 method. In the initial four cycles, CDDP produced a major nephrotoxic effect of average 10.27 ml/min/1.73m(2) (p < 0.01) fall in GFR. This then gradually declined to a plateau of an average decline in GFR of 7.76 and 7.31 ml/min/1.73m(2) (p=0.000) after the 5th and 6th cycle respectively., Conclusion: CDDP produced an early nephrotoxicity which was manifested by a significant decline in GFR in each cycle. Tc-99m PSC 2 method for GFR estimation should be used periodically for the early detection of nephrotoxicity induced by CDDP.

Objectives: The single-sample Tc-diethylenetriamine penta-acetate (DTPA) clearance method by Christensen and Groth is recommended by the Radionuclides in Nephrourology Committee on Renal Clearance for use in adults with an estimated glomerular filtration rate (GFR) > or = 30 ml/min. The purpose of this study was to test a new Tc-DTPA single-sample low clearance formula for GFR lesser than 30 ml/min., Methods: Twenty-one adult patients (29 investigations) were included. Reference clearance was calculated with both Cr-EDTA and Tc-DTPA according to Brøchner-Mortensen with samples drawn between 3 and 24 h. Single-sample clearance was calculated from a 24 h sample using the low clearance formula(Equation is included in full-text article.) C(t) is the activity of the tracer in the plasma sample t minutes after the injection and Q0 is the injected amount. ECV is the extracellular volume in ml defined as the distribution volume of the tracer. ECV is estimated from the body surface area as ECV=8116.6xbody surface area-28.2., Results: The mean difference between reference and Tc-DTPA single-sample clearance was -0.5 ml/min (SD 1.0 ml/min) for Tc-DTPA and -0.8 ml/min (SD 1.2 ml/min) for Cr-EDTA as reference clearance., Conclusion: In adult patients it is possible, even with GFR lesser than 30 ml/min, to get an accurate determination of Tc-DTPA plasma clearance from a single sample using the mean sojourn time approach. The blood sample should be obtained about 24 h after injection of the GFR tracer.

Objective: Dietary restriction (DR) without malnutrition is widely acknowledged to prolong lifespan in laboratory animals. Evidence suggests that DR retards age-related decline in protein turnover of most organs. However, there has been no report about hepatic serum glycoprotein catabolism under DR. In the current study, we evaluate the hepatic uptake of asialoglycoprotein in ICR mice with DR by measuring the plasma clearance of technetium-99m galactosyl human serum albumin (Tc-GSA)., Methods: The amount of food supplied to the restricted mice was 70% of that consumed by the mice fed ad libitum (AL). The regimen was initiated at the age of 7 weeks and terminated after the age of 44 weeks. The plasma clearance of Tc-GSA was measured at the age of 7 weeks, 14 weeks, 28 weeks, and 42 weeks., Results: The restricted animals showed a marked decrease in their body and liver weight, and hepatic uptake of Tc-GSA per liver weight in the restricted mice was greater than that in the mice fed AL. On the other hand, the Tc-GSA plasma clearance in the mice fed AL was stable during the study period, and that in the restricted mice showed no change with age either, and those in the two groups were similar. In addition to the receptor function, there was no difference in the expression of mRNAs of the asialoglycoprotein receptor between the two groups. Serum concentrations of cholinesterase and hepatic mRNAs of glutamine synthetase in the restricted mice were higher than those in the mice fed AL. Serum levels of amino acids in the restricted mice were lower than those in the mice fed AL., Conclusions: The data presented here show that the DR did not affect the capacity of hepatic serum glycoprotein catabolism, whereas several protein metabolic pathways were affected.

Objective: To evaluate the effect of infection with bovine respiratory syncytial virus (BRSV) on clearance of inhaled antigens from the lungs of calves., Animals: Eleven 6- to 8-week-old Holstein bull calves., Procedures: Aerosolized (99m)technetium ((99m)Tc)-labeled diethylene triamine pentacetate (DTPA; 3 calves), commonly used to measure integrity of the pulmonary epithelium, and (99m)Tc-labeled ovalbumin (OA; 8 calves), commonly used as a prototype allergen, were used to evaluate pulmonary clearance before, during, and after experimentally induced infection with BRSV or sham inoculation with BRSV. Uptake in plasma (6 calves) and lung-efferent lymph (1 calf) was examined., Results: Clearance of (99m)Tc-DTPA was significantly increased during BRSV infection; clearance of (99m)Tc-OA was decreased on day 7 after inoculation. Clearance time was correlated with severity of clinical disease, and amounts of (99m)Tc-OA in plasma and lymph were inversely correlated with clearance time. Minimum amounts of (99m)Tc-OA were detected at time points when pulmonary clearance of (99m)Tc-OA was most delayed., Conclusions and Clinical Relevance: BRSV caused infection of the respiratory tract with peak signs of clinical disease at 7 or 8 days after inoculation. Concurrently, there was a diminished ability to move inhaled protein antigen out of the lungs. Prolonged exposure to inhaled antigens during BRSV infection may enhance antigen presentation with consequent allergic sensitization and development of chronic inflammatory lung disease., Impact for Human Medicine: Infection of humans with respiratory syncytial virus early after birth is associated with subsequent development of allergic asthma. Results for BRSV infection in these calves suggested a supportive mechanism for this scenario.

Previous investigations into the functional responses of the surviving nephrons following reductions in renal mass have been performed largely in anaesthetized animals and have taken little account of how the compensatory changes develop with time. The present study has assessed a method for determining glomerular filtration rate (GFR) in unrestrained, uncatheterized, conscious rats (plasma disappearance of (99m)Tc-diethylenetriamene pentaacetic acid (DTPA)) and has used this method to document the time course of the changes in GFR over a 32 day period following uninephrectomy or 5/6 nephrectomy. Concurrent measurements of excretion rates and of the clearance of lithium (the latter being an index of end-proximal fluid delivery) provided information on changes in overall tubular function and segmental reabsorption. After uninephrectomy, the GFR of the remaining kidney (compared with that of a single kidney of sham-operated animals) increased maximally (by approximately 50%) within 8 days; after 5/6 nephrectomy, the increase in the GFR of the remnant kidney was maximal (at approximately 300%) within 16 days. Overall excretion rates of sodium and potassium were well maintained in partially nephrectomized animals throughout the period of study, while the excretion of water increased (by approximately 30% after uninephrectomy and by approximately 120% after 5/6 nephrectomy), partly as a result of the compensatory increases in GFR but mainly as a consequence of moderate (after uninephrectomy) or marked (after 5/6 nephrectomy) reductions in fractional reabsorption. During the early period after 5/6 nephrectomy, potassium excretion sometimes exceeded the filtered load, indicating net secretion. Lithium clearance data indicated that the changes in tubular function after 5/6 nephrectomy include a reduction in fractional reabsorption in the proximal tubule, whereas after uninephrectomy any such effect on the proximal tubule is minor and transient.

Objectives: To find an improved method of determining renal sufficiency by exploring power functions for estimating normal value, E(arg), single compartment glomerular filtration rate (G1), rate constant (gamma) and renal sufficiency index, RSI = gamma/E(gamma) = G1/E(G1), using compartment volume (V), patient mass ( W), patient age (A), patient height (H), and sex (S). To present the best estimator of normal, E(G1) = f(V, W)., Methods: One hundred and thirty 99mTc-diethylenetriaminepentaacetic acid (99mTc-DTPA) combined imaging and G1 studies in 97 children were screened by findings and history to obtain 44 normal studies of patients 1.46-18.5 years of age with blood samples at 109 (90-214) and 152 (120-246) min. Normal studies were used to generate predictive formulae., Results: For power functions, [equation: see text] the statistically acceptable formulae in descending order of adjusted R2 were f(V, W), f(V,A), f(V,H), f(V), f(W,A,H), f( W), f(H) and f(A). Relationships of the body surface area type, f(W, H, S) and f(W, H), were statistically unwarranted. Kleiber's law, E(G1) proportional to W(3/4), with E(G1) = 6.9190W(0.7618) found here, allowed confirmation of GFRinulin approximately 0.87G1. The best estimator is f(V, W) = 10.998V(0.64717 W(0.20185), and may relate to a volumetric measure of body habitus. To verify methods, Monte Carlo simulation of the glomerular filtration rate (GFR) and f(V, W) was performed and yielded less than 5% precision error, 98% of the time. Normal RSI from f(V, W) had the smallest standard deviation, 11.3%, no regression bias over a six-fold range on a Bland-Altman ratio plot, p = 0.4, and good agreement with clinical classification at 95% specificity (RSI > 0.8589, Cohen's Kappa 0.70+/-0.062 (mean+/-bootstrap standard error)., Conclusions: The best RSI from f(V, W) is RSI = 90.927gammaV(0.35283)W(-0.20185) and should detect mildly (14.1%) reduced renal sufficiency.

Objective: To find an applicable condition of the single-plasma-sample method (SPSM) to measure the glomerular filtration(GFR) with (99m)Tcj Diethylene Triamine Pentaacetic Acid ((99m)Tc-DTPA), and predict the value of (99m)Tc-DTPA plasma clearance by dual plasma sample method (DPSM ) from that by SPSM., Methods: Three hundred and thirty five patients with chronic kidney disease (CKD) were selected (192 males and 143 females). The average age was 51.91+/-14.76 years. The GFR was determined simultaneously by 2 methods: (1) SPSM (sGFR); (2) DPSM (tGFR), using DPSM as reference standard, sGFR calculated from the different SPSM was compared with tGFR. An equation was developed to predict tGFR from sGFR. GFR estimated by abbreviated Modification of Diet in Renal Disease (MDRD) equation (aGFR) was evaluated as the criterion in selection of DPSM and SPSM. The condition that DPSM could be substituted by SPSM in GFR measurement was given., Results: When tGFR >or= 30 mL/(minx1.73 m(2)), all of the sGFR were significantly correlated with tGFR. Among them, Watson modified Christensen and Groth's equation at sample time=240 min tended to be the most accurate (r=0.977, RMSE=10.91), and tGFR could be predicted from sGFR using the equation: Predicted tGFR [mL/(minx1.73 m(2))]=7.755 4+0.789 3xsGFR+0.002 4 xsGFR2 (n=297, r2=0.959 1, P<0.001). When aGFR was less than 50 mL/(minx1.73 m(2)), the diagnostic sensitivity of tGFR<30 mL/(minx1.73 m(2)) was 94.7%, and recommended as the criterion in selection of DPSM and SPSM., Conclusion: When aGFR >or=50 mL/(minx1.73 m(2)), DPSM can be substituted by SPSM in GFR measurement.

Objectives: Glomerular filtration rate (GFR) may be estimated from a single plasma sample measurement using empirical equations. This method forms the basis of international guidelines on GFR measurement. New guidelines have recently been recommended by the British Nuclear Medicine Society (BNMS). These use the slope-intercept technique in which several samples are obtained. Quality control of measurement may be achieved by comparison with the individual single-sample values. This paper compares international guideline single-sample estimates of GFR with the new BNMS method and derives an improved general single-sample equation., Methods: GFR measurements using Tc-DTPA were performed on 180 adults and 100 children using samples at approximately 2 h and 3 h and a further 45 adults with samples at 2, 3 and 4 h. The two-sample values obtained using the BNMS guideline method were compared to one-sample estimates obtained using (1) international guidelines and (2) a new equation derived from the data. The new equation was evaluated in a further 145 subjects., Results: The international guidelines technique had systematic differences between the one-sample and two-sample estimates of GFR. The new equation had minimal systematic error and reduced random error (standard error of the estimate 4.5 ml . min per 1.73 m)., Conclusions: There were significant differences between GFR values obtained using the international guidelines single-sample method and the slope-intercept method described in the BNMS guidelines. The new equation described in this paper gave considerably improved agreement and is recommended if single-sample estimates are to be used as quality control for BNMS guideline measurements.

Objectives: To develop an equation to predict dual plasma sample method (DPSM) (99m)Tc-diethylene triamine pentaacetic acid ((99m)Tc-DTPA) plasma clearance from single plasma sample method (SPSM), and to clarify the condition in which DPSM can be substituted by SPSM in measurement of glomerular filtration rate (GFR)., Methods: Patients with chronic kidney disease (CKD) were selected. Watson modified Christensen and Groth equation was used to calculate (99m)Tc-DTPA plasma clearance by SPSM (sGFR). The equation recommended by the Nephrourology Committee of the Society of Nuclear Medicine was used to calculate (99m)Tc-DTPA plasma clearance by DPSM (tGFR) in each patient. The difference between sGFR and tGFR was expressed as percent of the average of these two methods, and tGFR was predicted from sGFR. Plasma creatinine was measured by the kinetic picrate method, and GFR estimated by abbreviated modification of diet in renal disease (MDRD) equation (aGFR) and Cockcroft-Gault equation (cGFR) were evaluated as criteria in selection of DPSM and SPSM., Results: Three hundred and sixty-nine patients with CKD were selected (208 male and 161 female). The average age and body weight were 51.4 +/- 15.5 years and 67.2 +/- 12.5 kg, respectively. The causes of CKD were glomerular disease, renal arterial stenosis, chronic tubulointerstitial disease, and other causes or causes unknown. The average tGFR was 62.9 +/- 36.5 ml/min/1.73 m2, ranging from 1-180 ml/min/1.73 m2. sGFR was significantly correlated with tGFR (r = 0.9194, p < 0.001), but widely scattered when tGFR <30 ml/min/1.73 m2; in contrast, then tGFR was > or =30 ml/min/1.73 m2, the difference was constant (-1.1%, 95% confidence interval -18.3%, 16.1%), and tGFR could be predicted from sGFR using the equation: predicted tGFR (ml/min/1.73 m2) = 7.4244 + 0.7318 x sGFR + 0.0022 x sGFR2 (n = 299, r2 = 0.9428, p < 0.001), and the difference decreased to 0.1%, 95% confidence interval (-15.8%, 16.0%). aGFR was better than cGFR in diagnosis of tGFR <30 ml/min/1.73 m2, the diagnostic sensitivity of a cut off value of aGFR = 45 ml/min/1.73 m2 was 91.8%, and recommended as a criterion in the selection of DPSM and SPSM., Conclusion: When GFR > or =30 ml/min/1.73 m2, tGFR can be predicted from sGFR, which will simplify the reference GFR measurement in clinical trials. sGFR becomes widely scattered when tGFR is less than 30 ml/min/1.73 m2. To obtain reliable reference GFR values, it is recommended that DPSM be used in clinical trials when aGFR is less than 45 ml/min/1.73 m2.

Objective: To compare glomerular filtration rate (GFR) measured via urinary clearance of inulin (UCI) with plasma clearance of technetium Tc 99m pentetate (99mTc-pentetate) and creatinine in dogs., Animals: 6 healthy Beagles and 18 Beagles with reduced renal function., Procedure: 13 blood samples were obtained between 5 and 600 minutes after i.v. bolus injections of (99m)Tc-pentetate and creatinine. Plasma clearance of (99m)Tc-pentetate was computed on the basis of 1, 2, or 13 samples, and plasma clearance of creatinine was computed on the basis of 2, 5, or 13 samples. During plasma clearance procedures, constant i.v. infusion of carboxyl carbon 14 inulin was begun and UCI was determined in urine collected from 90 to 120, 120 to 180, and 180 to 240 minutes. Clearance procedures were repeated in 12 dogs to evaluate reproducibility of results., Results: Significant association between UCI and plasma clearance was determined via all methods. However, plasma clearances were moderately to markedly different from UCI, depending on test substance, GFR, and sample numbers used for plasma clearance computations. Comparisons were particularly discordant when some methods of limiting samples were used to define plasma clearance., Conclusions and Clinical Relevance: Values derived from plasma clearance methods for (99m)Tc-pentetate and creatinine were not interchangeable with UCI results, which raises questions about their reliability as clinical research tools for measurement of GFR. Plasma clearance methods that are relative indices of renal function should not be interpreted as accurate measures of GFR without validation.

Background: Modeling of pharmacokinetic parameters and pharmacodynamic actions requires knowledge of the arterial blood concentration. In most cases, experimental measurements are only available for a peripheral vein (usually antecubital) whose concentration may differ significantly from both arterial and central vein concentration., Methods: A physiologically based pharmacokinetic (PBPK) model for the tissues drained by the antecubital vein (referred to as "arm") is developed. It is assumed that the "arm" is composed of tissues with identical properties (partition coefficient, blood flow/gm) as the whole body tissues plus a new "tissue" representing skin arteriovenous shunts. The antecubital vein concentration depends on the following parameters: the fraction of "arm" blood flow contributed by muscle, skin, adipose, connective tissue and arteriovenous shunts, and the flow per gram of the arteriovenous shunt. The value of these parameters was investigated using simultaneous experimental measurements of arterial and antecubital concentrations for eight solutes: ethanol, thiopental, 99Tcm-diethylene triamine pentaacetate (DTPA), ketamine, D2O, acetone, methylene chloride and toluene. A new procedure is described that can be used to determine the arterial concentration for an arbitrary solute by deconvolution of the antecubital concentration. These procedures are implemented in PKQuest, a general PBPK program that is freely distributed http://www.pkquest.com., Results: One set of "standard arm" parameters provides an adequate description of the arterial/antecubital vein concentration for ethanol, DTPA, thiopental and ketamine. A significantly different set of "arm" parameters was required to describe the data for D2O, acetone, methylene chloride and toluene - probably because the "arm" is in a different physiological state., Conclusions: Using the set of "standard arm" parameters, the antecubital vein concentration can be used to determine the whole body PBPK model parameters for an arbitrary solute without any additional adjustable parameters. Also, the antecubital vein concentration can be used to estimate the arterial concentration for an arbitrary input for solutes for which no arterial concentration data is available.

Rationale: It is generally known that scintigraphy of 99mTc diethylenetriamine pentaacetic acid-galactosyl human serum albumin (99mTc-GSA) is useful for assessing hepatic functional reserve. For hepatic functional indicators, the index of the calculated planar image has been used in previous studies. However, there have been few reports that suggest that the indicators calculated from static SPECT data would be useful for the assessment of hepatic function. The aims of this study were to establish a simple method for assessing hepatic functional reserve using the liver SPECT of 99mTc-GSA and to apply this method for rich stratification in patients with chronic hepatic diseases., Methods: A liver phantom (a 50% concentration of 99mTc solution) was used to compare the planar and SPECT methods. According to the definition of the new indicator, the liver SPECT of 99mTc-GSA was divided by a syringe SPECT of 99mTc-GSA and was called the liver uptake ratio (LUR). We correlated the LUR and the liver uptake ratio calculated according to the blood-sampling method. 99mTc-GSA SPECT was performed in 137 patients with hepatic diseases, including chronic hepatic diseases, and 20 healthy volunteers. The LUR was correlated between the formed subtypes for all subjects., Results: The acquired phantom-count ratio calculated by the SPECT method was more accurate than that acquired by the planar method. A good correlation was obtained between the LUR and the blood-sampling method (r = 0.971). The LUR was significantly lower in subjects with severe cirrhosis than in healthy subjects or those with chronic hepatitis and mild cirrhosis, and it was significantly lower in subjects with chronic hepatitis and mild cirrhosis than in healthy subjects. The LUR was significantly correlated with other hepatic function tests. Based on LUR, the chronic hepatic diseases were divided into two groups: Group A, with LURs 30% and higher, and Group B, with LURs below 30%. An LUR of 30% marked the 25th percentile of the mild-cirrhosis group. The cumulative survival rates were lower in Group B than in Group A., Conclusion: The SPECT method was superior to the planar method for assessing LURs. LUR was a suitable indicator of 99mTc-GSA clearance from the blood pool and of binding to the asialo-glycoprotein receptor. LUR is a simple and clinically useful indicator for the assessment of hepatic functional reserve in chronic hepatic diseases.

The objective of this study was to investigate clinical utility of a graphical method for estimating liver uptake and blood retention of 99mTc-DTPA-galactosyl human serum albumin (99mTc-GSA; DTPA is diethylenetriaminepentaacetic acid) using dynamic single photon emission computed tomography (SPECT) data. When considering the kinetics of 99mTc-GSA, if it is assumed that (1) 99mTc-GSA distributes only between blood and liver, and (2) no metabolism of 99mTc-GSA occurs during the observation period, a plot of liver counts versus cardiac blood pool counts should, theoretically, be a straight line. From the slope and y intercept of a regression line, coefficients for converting count based liver and blood pool data to the per cent injected dose (%ID) can be calculated. The applicability of this method was tested on dynamic SPECT data from 30 patients with liver dysfunction. To validate this method, plasma concentrations (%ID/ml plasma) at 6, 15 and 30 min after the injection were estimated by this method and compared with the measured ones. To investigate the clinical significance of the per cent liver uptake, the value obtained by this method was compared with the results of conventional liver function tests, including serum albumin, the hepaplastin test, prothrombin time and indocyanine green clearance. In every data set, a plot of liver counts to cardiac blood pool counts was fitted well by a straight line (P<0.00001). Estimated plasma concentrations by this method showed good correlation with the measured ones at 6, 15 and 30 min after the injection (r=0.748, 0.838, 0.875, respectively; P<0.0001). The liver uptake determined by this method showed good correlation with the results of conventional hepatic function tests (P<0.002). The graphical method could provide an accurate estimate of %ID of 99mTc-GSA in blood without the need for blood sampling. The liver uptake determined by this method could be a simple but useful quantitative indicator of hepatic function.

Unlabelled: The aim of this study is to assess the accuracy of the pre-existing single-plasma-sample method (SPSM) to measure the glomerular filtration rate (GFR) with Tc-99m-diethylenetriamine pentaacetic acid (Tc-99m-DTPA) in children and adolescents. In addition, the age-independent SPSM is evaluated with two algorithms (Bubeck and Russell) applied for Tc-99m-mercaptoacetyltriglycine (Tc-99m-MAG3) SPSM., Patients and Methods: The study was performed on 14 patients (12 men and 2 women; age range 3 to 19 yr) with renal diseases. Tc-99m-DTPA (5 MBq/kg) was injected intravenously and thereafter blood samples were taken at 5, 15, 60, 90, 120, 150 and 180 min via the indwelling tube. Radioactivity in the injection syringe and plasma was measured by means of a double-well single-plastic scintillation counter. The "true" GFR as a reference was determined by two methods: 1) 2-exponential curve fitting 7 samples (GFR7) and 2) 1-exponential curve fitting 3 samples between 90 and 150 min (GFR3) in a slow clearance phase. The GFR7 and GFR3 were searched for to the clearance (GFR1) estimated from a plasma concentration at various sample times by means of 3 equations designed for children (Groth & Aasted, Ham-I and -II) and 3 for adults (Christensen & Groth, Jacobsson, Itoh)., Results: All the SPSM showed close correlations (r > 0.95) with the reference methods. Among them, Jacobsson's equation at sample time = 120 min tended to be the most accurate (r = 0.9826, RMSE = 7.8 ml/min)). On the other hand, Ham-I's equation at sample time = 120 min was the most accurate, when it was referred to GFR3 in correction for overestimation (r = 0.9951, RMSE = 4.60 ml/min). The Bubeck and Russells' algorithms showed that the regression equation between the GFR7 and the estimates was different in 2 groups of adults (49 cases) and children/adolescents., Conclusion: Our study indicates that Jacobsson's and Christensen & Groth's equations designed for adults are also applicable in determining the GFR with Tc-99m-DTPA in children and adolescents. The algorithms applied for age-independent SPSM with Tc-99m-MAG3 appears to be applicable to SPSM with Tc-99m-DTPA in children, adolescents and adults, but the single age-independent equation with Tc-99m-DTPA will need further investigations.

Objective: To compare renal clearance of technetium Tc 99m pentetate with plasma clearance by use of a glomerular filtration rate technique in pigs from 3 to 24 weeks of age., Animals: 24 female pigs., Procedure: At the time of investigation, 5 pigs were 3 weeks old, 6 pigs were 6 weeks old, 8 pigs were 12 weeks old, and 5 pigs were 24 weeks old. Plasma clearance of technetium Tc 99m pentetate was measured by the use of a single injection technique followed by collection of multiple blood samples until 5 hours after the injection. Simultaneously, urine was collected through a urinary catheter, and the renal clearance of technetiumTc 99m pentetate was calculated. Plasma clearance of technetium Tc 99m pentetate was correlated with the renal clearance (r = 0.95). Plasma clearance was higher than renal clearance at all ages (mean, 5.8%), indicating extrarenal clearance of technetium Tc 99m pentetate or methodologic errors. Volume of distribution increased with increasing age but decreased as a fraction of body weight., Conclusions: Plasma clearance of technetium Tc 99m pentetate estimates renal clearance with acceptable precision when using single injection technique and multiple biood samples in pigs from 3 to 24 weeks of age.

Unlabelled: The plasma sample method following a single injection of radioactive markers has been proved to be simple and accurate for the determination of glomerular filtration rate (GFR) in clinical practice. The aim of this study was to assess clinical accuracy of single-, two- and multi-sample methods., Methods: The study was performed on 50 patients with various degrees of renal dysfunction (29 males and 21 females; aged 27 to 90 years). As a reference the true GFR (GFRt) was determined by means of the two-compartment model curve fitting 10 plasma samples following a single-injection of 99mTc-DTPA. The GFRt was compared to the GFR estimated by the Christensen and Groth's single-sample (GFRcg), two-sample (GFR2s) and multi-sample (GFRm) between 75 and 300 min after the injection. The GFRs by two- and multi-sample methods were determined with the slope and intercept algorithm and its overestimation was corrected by Brochner-Mortensen's formula., Results: In 49 patients with GFR between 12 and 169 ml/min/1.73 m2, the standard deviation of difference (95% limits of agreement) between GFRt and GFRcg at 180 min was 6.513 ml/min/l73 m2 (-16.5 approximately 9.5 ml/min/1.73 m2), which was somewhat closer than 7.311 ml/min/1.73 m2 (-12.5 approximately 16.5 ml/min/1.73 m2) in GFR2s in slow clearance phase at 120 min and 240 min. However, the single-sample method tended to show some scattering in GFR below 30 and above 140 ml/min/ 1.73 m2. On the contrary, the 2-sample method tended to be scattered in GFR above 120 ml/min/ 1.73 m2., Conclusion: In view of its accuracy and technical simplicity, the single-sample method is first choice in a routine practice. The two-sample method is essential of choice for a patient in whom the GFR is expected to be below 30 ml/min/1.73 mi2. These two methods may be chosen selectively in dependence on the preserved renal function which is expected at time of the test.

Airway wall edema, prominent in inflammatory airways disease, may alter barrier properties at the airway air-liquid interface such that normal absorption of soluble substances into the airway circulation is altered. We studied the effects of bradykinin-induced airway wall edema on the clearance of the soluble tracer technetium-99m-labeled diethylenetriamine pentaacetic acid ((99m)Tc-DTPA) from subcarinal airways in sheep (n = 8). (99m)Tc-DTPA (6-10 microl) was delivered by a microspray nozzle inserted through a bronchoscope to a fourth-generation bronchus both before and 1 h after bradykinin (20 ml; 10(-6) M) had been infused through a cannulated and perfused bronchial artery. Airway retention (by scintigraphy) and blood levels of radiolabel were monitored for 30 min after the local deposition of (99m)Tc-DTPA. During control conditions, 85-90% of the tracer cleared from the deposition site within 30 min. The maximum blood level during that time was 17% of the total delivered tracer. However, 1 h after bradykinin infusion, there was significant retention of the marker at the deposition site with clearance within 30 min reduced to 63-70% and decreased blood levels of radiolabel (8%; both P < 0.05). These results demonstrate that moderate airway wall edema alters blood uptake and removal of soluble substances delivered to the subcarinal airways. We suggest that the interplay between vascular and mucociliary clearance routes will impact the resident time for clearance of soluble air toxins and/or therapeutic agents from the epithelial surface.

Although a role for the airway circulation in the clearance of inhaled particles is generally assumed, there is little information to confirm its importance. We studied the effects of decreased bronchial blood flow on the uptake of the soluble tracer technetium=99m-labeled diethylenetriamine pentaacetic acid (99mTc-DTPA) from subcarinal airways in sheep (n = 7). The bronchial artery was cannulated and perfused with autologous blood at a control flow (0.6 mL/min/kg) or when the perfusion pump was stopped (no flow). (99m)Tc-DTPA (6-10 microL) was delivered by a microspray nozzle inserted through a bronchoscope to a fourth-generation bronchus both during control blood flow conditions and no-flow conditions. Airway retention (by scintigraphy) and blood uptake were monitored for 30 min after the local deposition of (99m(Tc-DTPA. During control flow conditions, 30 min after the delivery of the radiolabel, 21% of the tracer remained at the deposition site. Of the total delivered tracer, maximum blood uptake was 18% (n) = 3). When bronchial perfusion was stopped, airway retention 30 min after deposition increased to 43%, and maximum blood uptake decreased to 7% of the total delivered tracer. Although mucociliary clearance was not directly measured, radiolabel tracer was observed to move progressively from the deposition site up to larger airways and contributed to the overall removal of tracer from the site of deposition during both flow conditions. However, these results demonstrate that decreased bronchial perfusion increases airway retention by limiting vascular uptake of the soluble tracer. These results emphasize the importance of normal perfusion of the airway vasculature for uptake of therapeutic agents delivered specifically to the conducting airways.

Bioavailability of an aerosolized anti-inflammatory protein, soluble interleukin-4 receptor (IL-4R), was measured in patients with asthma using two different aerosol delivery systems, a prototype aerosol delivery system (AERx tethered model, Aradigm, Hayward, CA) and PARI LC STAR nebulizer (Pari, Richmond, VA). Regional distribution of the drug in the respiratory tract obtained by planar imaging using gamma camera scintigraphy was utilized to explain the differences in bioavailability. The drug, an experimental protein being developed for asthma, was mixed with radiolabel 99mTechnetium diethylene triaminepentaacetic acid (99mTc-DTPA). Aerosols were characterized in vitro using cascade impaction (mass median aerodynamic diameter [MMAD] and geometric standard deviation [GSD]); the AERx MMAD 2.0 microm (GSD 1.35), the PARI 3.5 microm (GSD 2.5). Four patients with asthma requiring maintenance aerosolized steroids were studied. First, regional volume was determined utilizing equilibrium 133Xe scanning. Then, after a brief period of instruction, patients inhaled four breaths of protein using AERx (0.45 mg in total) followed 1 week later by inhalation via PARI (3.0 mg nebulized until dry). Each deposition image was followed by a measurement of regional perfusion using injected 99mTc albumin macroaggregates. Deposition of 99mTc-DTPA in the subjects was determined by mass balance. Regional analysis was performed using computerized regions of interest. The regional distribution of deposited drug was normalized for regional volume and perfusion. Following each single inhalation, serial blood samples were drawn over a 7-day period to determine area under the curve (AUC) of protein concentration in the blood. Median AUC(AERx)/AUC(PARI) was 7.66/1, based on the amount of drug placed in each device, indicating that AERx was 7.66 times more efficient than PARI. When normalized for total lung deposition (AUC per mg deposited) the ratio decreased to 2.44, indicating that efficiencies of the drug delivery system and deposition were major factors. When normalized for sC/P and (pU/L)xe ratios (central to peripheral and upper to lower ratios are parameters of regional distribution of deposited particles and regional per- fusion ['p']), AUC(AER)x/AUC(PARI) further decreased to 1.35, demonstrating that peripheral sites of deposition with the AERx affected the final blood concentration of the drug. We conclude that inhaled bioavailability of aerosolized protein, as expressed by AUC, is a quantifiable function of lung dose and regional deposition as defined by planar scintigraphy.

99Tcm-Diethylenetriaminepentaacetic acid (99Tcm-DTPA) has been postulated to be more bound to plasma proteins than are other radiopharmaceuticals used for measurement of glomerular filtration rate (GFR). The results of protein binding experiments are, however, highly related to methodology. The aim of the present study was to compare the protein binding of the 99Tcm-DTPA preparation we use in our daily routine with that of the other five 99Tcm-DTPA preparations available and with other GFR tracers by using the same ultrafiltration method. Protein binding was studied in vitro after incubation in donor plasma and in vivo after single injection in patients. A correction for the uneven distribution of ultrafiltrable ions ('Donnan effect') was included. Quality control of six 99Tcm-DTPA preparations performed with thin layer chromatography showed a high labelling efficiency (96.2-99.9%). The in vitro protein binding ranged from 9.25% to 11.12%. The in vitro protein binding of 99Tcm-DTPA was not significantly different from that of 51Cr-ethylenediaminetetraacetic acid (51Cr-EDTA) and 125I-iothalamate (10.99% vs 12.15%, and 9.55%). There was no difference in the in vivo protein binding of 99Tcm-DTPA 5 and 40 min after injection (13.28% vs 12.58%), and there was no difference in the protein binding of 99Tcm-DTPA and 51Cr-EDTA (12.93% vs 12.54%). In conclusion, in vitro and in vivo protein binding of 99Tcm-DTPA was 10-13%. The protein binding was not different from the binding of 51Cr-EDTA and 125I-iothalamate.

The purpose of this study was to evaluate simplified methods for estimation of Technetium Tc 99m (99mTc)-pentetate and orthoiodohippurate I 131 (131I-OIH) plasma clearance in dogs and cats with 1 and 2 blood samples. Plasma clearances were calculated after a bolus injection of 1.85-11.1 MBq of 99mTc-pentetate and 131I-OIH with a 2-compartment model based on a 12-point curve as a reference method in 21 dogs and 18 cats. Three 2-sample and 3 single-sample methods were investigated. The method yielding the smallest standard deviation of the difference between the reference method and the simplified method was selected as the optimal one. Linear regression analysis was performed between the reference method and the simplified method and coefficient of determination (R2) was calculated. For 99mTc-pentetate plasma clearance, the optimal 2-sample method was the one with a mono-compartment model with samples taken at specific times. For 131I-OIH plasma clearance, the estimation was improved slightly by raising the clearance calculated with a mono-compartment model to the power of an empirically determined parameter. The optimal single-sample method was the one with a linear quadratic regression between the volume of distribution of the tracer at a specific time and the clearance calculated with 12 samples. Two-sample methods performed significantly better than did single-sample methods. The conclusion is made that 99mTc-pentetate and 131I-OIH plasma clearances can be estimated in dogs and cats with 1 or 2 blood samples with a reasonable margin of error compared to plasma clearances calculated with a 2-compartment model and 12 blood samples.

Nontutimorous decrease in 99mTc-GSA accumulation has not been well covered in the literature. Understanding of this phenomenon is, however, essential for accurate evaluation of regional hepatic function. Scintigrams (transaxial SPECT) of 269 patients who underwent 99mTc-GSA liver scintigraphy were reviewed for the presence of nontumorous decreases in 99mTc-GSA accumulation. Nontumorous decreases in 99mTc-GSA accumulation were seen in 32 of 269 patients (12%). In 16 of the 32 patients (6%), nontumorous decreases in 99mTc-GSA accumulation corresponded to regional decrease in portal venous flow. The causes of such decrease in portal venous flow were portal thrombus of hepatocellular carcinomas in eight patients, portal venous stenosis or occlusion by hilar cholangiocarcinomas in five patients, inter alia. In eight patients (3%), the regions with decreased 99mTc-GSA accumulation correlated with massive hepatic necrosis in fulminant hepatitis, scar in hepatitis, or confleuent in portal venous flow, lobar biliary stasis, or both. In four patients (1.5%), the exact causes of nontumorous decrease in 99mTc-GSA accumulation could not be determined.

Scintigraphy with 99mTc-diethylenetriamine pentaacetic acid galactosyl human serum albumin (99mTc-GSA) was performed on 102 patients, then the hepatic extraction fraction (HEF), the rate constant for liver uptake of the tracer from the blood (K1) and the hepatic blood flow index (HBFI) were determined by spectral analysis. The HEF, K1 and HBFI values correlated moderately or closely with various indices of hepatic function, and the HEF and K1 values decreased according to the stage of liver dysfunction. The HEF and K1 values linearly and nonlinearly correlated with HH15 and LHL15, respectively. The HEF, K1 and HBFI values for the irradiated portion of 20 patients before and alter irradiation were compared. The HEF value in patients with a cirrhotic liver significantly (p < 0.002) decreased compared with that in patients with a normal liver at a dose of less than 40 Gy, whereas the HBFI value in patients with a normal liver significantly (p < 0.05) decreased compared with that in patients with a cirrhotic liver at a dose of 40 Gy or greater. This method appears to be a simple, non-invasive and useful tool with which to quantitatively evaluate liver function and it also helps clarify changes in regional function of the irradiated liver.

The aim of this study was to assess the clinical validity of single-sample methods and gamma camera uptake methods with 99mTc-DTPA for the estimation of the glomerular filtration rate (GFR). The study was performed in 50 patients with various degrees of renal function (29 males and 21 females; age 27-90 yrs; serum creatinine level 0.34-6.49 mg/dl). As a reference the "true" GFR (GFRt) was determined from plasma clearance by means of the two compartment model curve fitting 10 plasma samples. The GFRt of more than 30 ml/min in 46 patients was compared to the GFR which was estimated with 7 single-sample methods, two gamma camera uptake methods and 24-hour endogenous creatinine clearance (24hCcr). Close correlation was observed in all single-sample methods. The highest linear correlation was observed in the Christensen and Groth's method rewritten by Watson for a 180-min plasma sample (r = 0.991, see = 5.84 ml/min). The smallest random error was observed in the Groth and Aasted's method for a 180-min plasma (r = 0.989, see = 4.31 ml/min/1.73 m2). Our method was lowest in % absolute difference analysis (mean = 4.10%). The gamma camera uptake methods correlated significantly with the GFRt (r = 0.746-0.774), but were less reliable than any of the single-sample methods (see = 15.41 ml/min-19.14 ml/min). The lowest correlation was observed in the 24hCcr (r = 0.698, see = 50.76 ml/min/1.73 m2). The single-sample method was more accurate than the gamma camera method, and the gamma camera method was more accurate than 24hCcr. The single-sample method should be recommended for the accurate determination of the GFR with 99mTc-DTPA in a patient with mild to moderate renal dysfunction.

Objective: To determine the effect of number of blood samples and sampling times on plasma clearance of technetium Tc 99m pentetate (Tc99mP) and orthoiodohippurate sodium I 131(OIH)., Animals: 20 dogs and 14 cats., Procedure: Plasma clearances of OIH and Tc99mP were calculated by use of a 2-compartment model, on the basis of a 12-point curve as a reference method. Plasma clearance was calculated by use of all possible combinations of 4 to 11 samples. Time schedule yielding the smallest difference from the reference method was considered to be optimal. Regression analysis was performed between the 12-point model and models using a reduced number of samples., Results: SD of the difference between the 12-point clearance and the models with reduced numbers of samples increased when the number of samples decreased. The SD of the difference between 12-point clearance and 4-point clearance was 4.17 ml/min for OIH and 0.94 ml/min for Tc99mP in dogs and 0.45 ml/min for OIH and 0.11 ml/min for Tc99mP in cats. Optimal schedules were distributed logarithmically and included an early sample at 5 or 10 minutes, a late sample at 2.5, 3, 4, or 5 hours for OIH, and a late sample at 4 or 5 hours for Tc99mP., Conclusions and Clinical Relevance: Plasma clearances of OIH and Tc99mP can be accurately calculated in dogs and cats by use of a single-injection 2-compartment pharmacologic model with a reduced number of blood samples, resulting in an acceptable margin of error.

Unlabelled: Glomerular filtration rate (GFR) is an important index of renal function. The aim of this study was to compare the GFR with 99m Tc. DTPA without urine collection estimated with three, two and single-sample methods. We studied 148 patients (54 women and 94 men, 3-84 years old) with diverse renal diseases. After intravenous administration of Tc99m DTPA three (90-120-180 min. Method 1; n = 44) or two (120 and 180 min or 180 and 240 min Method 2, n = 104) blood samples were taken. The GFR (ml/min) were calculated using monoexponential analysis, or with only the sample of the 180 or 240 min with the methods of Jacobsson, Russel, Groth-Aasted, Dakubu and Constable., Results: 1) In 37/148 (25%) the GFR by Method 1-2 was less than 30 ml/min. All the single-sample methods did not perform well. 2) in 107/148 (75%) the GFR using method 1 and 2 was superior to 30 ml/min. The single sample methods showed clinically acceptable absolute error differences with method 1 and 2. However, we cannot suggest a preferable one single sample method that covers all the range of GFR that we analyzed. In conclusion, the 2 sample technique provides an estimate of GFR and we also suggest ultrafiltering the plasma before measuring radioactivity to give better accuracy in calculating GFR.

Background: Changes in glomerular filtration rate (GFR) provide a valuable indicator of the progression of diabetic nephropathy. GFR is most commonly measured by the plasma clearance of radioisotopes, however, use of iohexol, a non-ionic radiocontrast medium, is a recently described alternative and has shown good agreement with inulin clearance. A one-compartment model is used for calculating GFR in most Australian centres but a two-compartment model is more accurate., Aims: To set up a non-radioisotopic method for assessment of GFR using iohexol, and to compare this with the currently used 99mTc-diethylene-triamine-penta-acetic acid (DTPA) method. Secondly, to compare GFR results using an unmodified one-compartment model with a one-compartment model subjected to the Brochner-Mortensen modification., Methods: Twenty-one patients with diabetes had assessment of GFR with simultaneous measurements of 99mTc-DTPA and iohexol plasma clearance. Plasma clearance was determined by the slope intercept method and then modified according to the Brochner-Mortensen equation. Plasma iohexol concentrations were determined by capillary electrophoresis., Results: There was no significant difference between iohexol and 99mTc-DTPA derived GFR values, difference 4.3+/-7.7 mL/minute (mean+/-SD). This was despite 99mTc-DTPA protein binding demonstrated in the range of 5-10%. Comparison of GFR results using an unmodified one-compartment model with a Brochner-Mortensen corrected one-compartment model showed higher GFR values with the former, in the range of 20-30% for GFR values > 100 mL/minute., Conclusion: Iohexol provides an efficient alternative to radioisotopic methods for serial measurement of GFR in diabetic patients with hyperfiltration, incipient and overt nephropathy. A one-compartment model with its inherent overestimation of GFR should be replaced by the Brochner-Mortensen modified one-compartment model.

Error estimates for arteriovenous difference were calculated by two models, a lag time model and a compartmental model, using Tc99m-diethylenetriaminepentaacetic acid (DTPA) plasma clearance curves from 40 subjects and Tc99m-MAG3 (mercaptoacetyltriglycine) curves from 18 subjects. It was found that correcting for the effect of the initial bolus largely cancelled the conventional arteriovenous difference, so that the net error was negligible.