Assessment of accuracy and precision of 99mTc-HEPIDA clearances determined by means of a simplified method

BACKGROUND: The aim of the present study was the assessment of the accuracy and precision of our own simplified method for the determination of 99mTc-HEPIDA liver clearance. MATERIAL AND METHODS: It has been assumed that archived results of plasma clearance (ClPl) and hepatic (ClHp), determined by means of multisample methods, could be legitimately used as a reference standard. The accuracy and precision of the simplified method was assessed by means of a Monte Carlo method alternatively utilizing three blood sampling times (T) of 68, 75 and 83 minutes post i.v. administration of 99mTc-HEPIDA. The corresponding alternative three urine voiding times (Y) were: 75, 80, and 95 min p.i. The analysed model was created accepting values of ClPl and ClHp, of administered activity Ap and parameters of biexponential function, describing the concentration C(t) decrease of the radiopharmaceutical (RF) in plasma during time as real values. Using the function C(t) for each individual, the plasma concentrations of RF at three sampling times, urinary clearance (ClPl - ClHp), and voided activity (AUr(Y)) were calculated. Simulated random errors were added to the assumed blood sampling times T and to voiding time Y. To the activity Ap and AUr(Y), and RF plasma concentrations random errors were added, assuming normal distribution with relative SD from 0 to 5% and then clearance values were computed. For each process there were 5000 repeated simulated determinations. The accuracy of the simplified methods was assessed by comparing mean values of simulated clearance computations with the reference. Comparison of standard deviations with mean uncertainties enabled us to gain insight into the degree of agreement of the estimator of relative uncertainty with the coefficient of variation as a measure of precision. RESULTS: There were strong correlations between the reference clearance values and the mean values of determinations by means of the simplified procedure (r > 0.93). The correlations were practically insensitive to the uncertainty of pipetting. The lines of regression differed slightly from the lines of identity, giving an indication that there was a systematic error involved; it amounted to +4 ml/min at ClPl = 60 ml/min and to -7 ml/min for ClPl of 370 ml/min. For ClPl a bias of +6 ml/min was found for a clearance value of 16 ml/min and –13 ml/min at ClPl > 300 ml/min. At uncertainty of pipetting of 2%, a precision of 6-7% was found for ClPl of 300 ml/min. For ClPl of 200 and 150 ml/min the corresponding precisions were 7–8% and 10%, respectively. For ClPl of 200, 150 and 100 ml/min the corresponding precisions were 10, 12 and 17%, respectively. These precisions are 5 percent worse than those that were obtained from determinations by means of multisampling procedures

Modification of a two blood sample method used for measurement of GFR with 99mTc-DTPA

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.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

Comparison of 99mTc-HEPIDA and 99mTc-MBrIDA from the standpoint of hepatic clearance determination - preliminary communication

BACKGROUND. In order to evaluate the functional capacity of the liver by means of clearance determination, the derivative of iminodiacetic acid (99mTc-HEPIDA) has been used in recent decades. Because of recent problems with manufacturing and delivery of 99mTc-HEPIDA, an investigation was undertaken with the aim of testing whether a more widely available 99mTc-MBrIDA could be used for clearance determination and whether hepatic clearance measured with the use of this compound provides a similarly useful test of hepatic function. MATERIAL AND METHODS. Comparative investigations were performed in 73 patients of both sexes. The state of the efficiency of liver parenchyma was determined based on seven widely used biochemical tests, i.e. levels of: bilirubin, albumin, and gamma globulin; activity of AST, ALT, GGTP, and prothrombin index. The clearances of both radiopharmaceuticals, 99mTc-HEPIDA and 99mTc-MBrIDA, were determined by means of multisample technique. The results of determination were correlated among themselves and with the results of biochemical tests. The set of results of all estimations allowed a factorial analysis to be performed to find a common factor and to compute the values of factor loadings in particular tests. RESULTS. Obvious correlation between plasma and hepatic clearances of both radiopharmaceuticals was obtained and between plasma clearance of 99mTc-MBrIDA and hepatic clearance of 99mTc-HEPIDA. Correlation coefficients of 99mTc-MBrIDA clearance and the biochemical test results attained somewhat lower values than for 99mTc-HEPIDA clearance. Similarly, values of χ2 test of independence of 99mTc-MBrIDA clearances and test results were also less close than for 99mTc-HEPIDA clearances. Factorial analysis showed that common factor loading is greatest for hepatic clearance of 99mTc-HEPIDA; the values of two loadings of 99mTc-MBrIDA clearances are very close, but somewhat lower than those for 99mTc-HEPIDA. CONCLUSIONS. From the performed investigations it is possible to conclude that 99mTc-MBrIDA clearances may be used for the evaluation of liver parenchyma performance, even if the results may not be as certain as those obtained using 99mTc-HEPIDA

Abstracts from the 20th International Symposium on Signal Transduction at the Blood-Brain Barriers

https://deepblue.lib.umich.edu/bitstream/2027.42/138963/1/12987_2017_Article_71.pd

Verification of 99mTc-Ethylenedicysteine (99mTc-EC) distribution model in the organism

Background: The aim of the present study was an attempt to verify the systemic distribution of 99mTC-ethylenedicysteine by means of the open two-compartment model. Methods: In order to accomplish this, 99mTc-EC clearance was determined in 21 patients as: two-compartmental model-based plasma clearance, and a urinary clearance, i.e. utilising the 99mTc-EC activity excreted with urine during a finite time interval. Results: There is a close correlation (r = 0.97) between the clearance values determined according to these two methods, and the rectilinear orthogonal correlation equation assumes a C1ECu = 1.03656C1ECp - 18.064 form. The slope of the line does not differ significantly from unity. The shift of the correlation line along the X-axis indicates a minor excretion of the radiopharmaceutical also by routes different from the urinary tract, e.g. with the bile. Conlusions: The performed comparison of the clearance values has proved that distribution of 99mTc-EC in the organism is consistent with the open two-compartment model

Pharmacokinetic characteristics of 99mTc-Ethylene-l-dicysteine (99mTc-EC)

Background: Ethylenedicysteine-99mTc (99mTc-EC) has been more and more commonly applied in dynamic studies as well as for clearance determinations. However, it was necessary to investigate in detail the pharmacokinetic characteristics of the radiopharmaceutical which may be important for its applicability in assessment of renal function. Results: Kidney images obtained from renoscintigraphy are characterised by excellent quality without visualisation of the organs adjacent to kidneys (liver, spleen). Renoscintigraphic curves demonstrate typical shapes with TMAX and T1/2 values not differing from the corresponding values obtained for other radiopharmaceuticals (99mTc-MAG3, 131I-OIH). In plasma, 99mTc-EC binds with proteins to a considerably lesser degree (c. 1/3) than 131I-OIH (c. 2/3), or 99mTc-MAG3 (> 9/10). No binding of 99mTc-EC with erythrocytes has been demonstrated, whereas 131I-OIH attaches to or penetrates the red blood cells (10-12%). 99mTc-EC is quickly excreted from the organism: 40 min after i.v. injection up to 70% of the administered radiopharmaceutical is found in urine, and at 1 and 1.5 h after the administration 80% and 95%, respectively. The distribution of 99mTc-EC in the organism can be described in a fully satisfactory way by means of an open two-compartment model, which allows this model to be used for clearance determinations. Comparison of the values of renal plasma clearance without collection of urine with the values determined by means of measurement of activity excreted with urine and mean blood concentration over a finite time interval leads to the conclusion that extrarenal plasma clearance of this compound (via the liver?) is negligible and amounts to c. 17 ml/min (5-6% of the total). The obtained correlation between clearance values for 99mTc-EC and 131I-OIH supports the contention that extrarenal excretion rate of 99mTc-EC (through the liver and bile ducts) is lower than the corresponding rates of either 131I-OIH or 99mTc-MAG3. A very close correlation between clearance values for 99mTc-EC and ERPF (131I-OIH clearance) and between their extraction constants (r = 0.91 and 0.92, respectively), allows for the introduction of 99mTc-EC to the assessment of renal function instead of 131I-OIH. Effective dose to the patient from unit activity of 99mTc-EC is comparable with that resulting from administration of other radiopharmaceuticals labelled with 99mTc