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R C Stadalnik

Publications and source records attributed to R C Stadalnik.

At least 37 records · Page 2Linked to original sources
PubMed1994

Evaluation of hepatocellular function by way of receptor-mediated uptake of a technetium-99m-labeled asialoglycoprotein analog.

UNLABELLED: We have developed a quantitative functional imaging study of the liver using a radiolabeled asialoglycoprotein analog, Tc-galactosyl-neoglycoalbumin. Heart and liver time-activity data can be transformed by automated kinetic analysis into asialoglycoprotein hepatocyte receptor concentration. Twenty-eight healthy controls, 46 patients with noncholestatic chronic liver injury and 11 patients with primary biliary cirrhosis were studied. Liver function was also assessed by Pugh modified-Child-Turcotte criteria, 14C-aminopyrine breath test and indocyanine green clearance (24 patients). RESULTS: (a) In normal controls with a Child-Turcotte criteria score of 5, receptor concentration ranged from 0.63 to 1.19 mumol/L, with a mean 0.83 +/- 2 S.D. 0.06 mumol/L, which was significantly higher (p < 0.001) than that of the patient group (mean receptor concentration = 0.44 +/- 2 S.D. 0.04 mumol/L). In cirrhotic patients with Child-Turcotte criteria score of 5, the mean receptor concentration was 0.60 +/- 2 S.D. 0.07 mumol/L, which was significantly lower than controls (p < 0.01). In end-stage cirrhosis (Child-Turcotte criteria score 11 to 15), a group in which patients died or required orthotopic liver transplantation within 1 yr, the mean receptor concentration was 0.35 +/- 2 S.D. to 0.07 mumol/L. The sensitivity and specificity for receptor concentration in relation to liver disease, with values above 0.65 mumol/L being normal, were 0.96 and 0.88, respectively. Receptor concentration correlated well with Child-Turcotte criteria score (r = 0.78, p = < 0.001), with aminopyrine breath test (r = 0.75, p = < 0.001) and with indocyanine green clearance (r = 0.88, p = < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Albumins↗
PubMed1994

Local identifiability of a receptor-binding radiopharmacokinetic system having measured parameters of known uncertainty.

Local identifiability was determined for a receptor-binding radiopharmacokinetic system that included measured parameters of known uncertainty. Healthy subjects and patients with severe liver disease were studied with [99mTc] galactosylneoglycoalbumin (TcNGA). Measurements during the 30-min dynamic imaging study included the count rate over liver and heart, the quantity of TcNGA injected Lo, and the fraction-of-injected dose per liter of sampled plasma f. Typical relative standard deviations for these measurements were 1, 0.2, and 5 percent, respectively. A four-state nonlinear model describing the hepatic and plasma time-activity data was then used to calculate the standard error se(pj) for model parameters representing receptor concentration [R]o, the TcNGA-receptor forward binding rate constant kb, extrahepatic plasma volume Ve, hepatic plasma volume Vh, and hepatic plasma flow F. Accounting for the measurement uncertainties of Lo and f did not significantly increase the standard errors for parameters [R]o, kb, Ve, Vh and F. When the relative errors of Lo and f were increased to 40%, the change in se(pj) ranged from 10 to 100%, with parameter Vh being the most sensitive. The exception was se(kb), the increase of which was less than 1%. Imaging studies with reduced [R]o, typically associated with patients with liver disease, resulted in greater increases in all estimated parameter errors except se(kb) which had a lower increase. Lastly, the error propagation introduced by direct measurement of the liver observational coefficients sigma 12 and sigma 13 was investigated by simulating changes in the relative standard deviation in parameters sigma 12 and sigma 13 from 0 to 40%. Imaging studies from healthy subjects showed no increase in se(pj).(ABSTRACT TRUNCATED AT 250 WORDS)

Albumins↗
PubMed1993

Measurement of functioning hepatocyte mass via [99mTc]galactosyl-neoglycoalbumin.

Technetium-99m-galactosyl-neoglycoalbumin (TcNGA) is a synthetic radiolabeled ligand specific for hepatic binding protein (HBP), a receptor that resides exclusively on hepatocytes. In vivo measurement of receptor concentration was obtained via kinetic analysis of liver and blood time-activity data obtained during the hepatic clearance of intravenously administered TcNGA. The purpose of this study was to assess receptor concentration as a measure of the functioning hepatocyte mass. Therefore, TcNGA and dual-injection indocyanine green maximal removal rate (ICG Rmax) studies were performed on nine patients with hepatic cirrhosis associated or not with hepatocellular carcinoma. Receptor concentration was compared with ICG Rmax, which is a validated method for the estimation of the functioning hepatocyte mass. The correlation coefficient was 0.76 (P = 0.017). It is concluded that HBP concentration ([HPB]o) as measured by functional imaging is a measure of functioning hepatocyte mass. This implies that measurement of an individual's receptor concentration by using nuclear medicine techniques provides an objective index of hepatic functional mass and supports attempts to rigorously evaluate [HBP]o for its clinical efficacy.

Aged↗
PubMed1993

Postprandial gastric motility in infants with gastroesophageal reflux and delayed gastric emptying.

Delayed gastric emptying of formula is observed in many infants with gastroesophageal reflux but the mechanisms responsible for this observation are not defined. Postprandial gastric motility was quantified using a perfused catheter placed into the distal stomach of five infants with gastroesophageal reflux and delayed gastric emptying of 99mTc-sulfur colloid-labeled formula. Five infants with reflux who exhibited normal emptying of formula served as the controls. Gastric motility indices were calculated for 60 min following a meal. Half the patients in each group were given metoclopramide following a 30-min recording period. In both groups, postprandial gastric motility was similar and characterized by minimal gastric contractions. Metoclopramide resulted in increased amplitude and duration of antral contractions, but no significant differences were noted between groups. The findings suggest that minimal delays in gastric emptying in infants with gastroesophageal reflux are not associated with significant alterations of postprandial gastric motility.

Bottle Feeding↗
PubMed1993

Quantitative assessment of hepatocellular function through in vivo radioreceptor imaging with technetium 99m galactosyl human serum albumin.

Technetium 99m diethylenetriaminepentaacetic acid-galactosyl human serum albumin is a newly developed analog ligand to asialoglycoprotein receptor, which is a hepatic cell surface receptor specific for galactose-terminated glycoproteins. Hepatic functional imaging, which yields estimates of asialoglycoprotein receptor concentration, was performed after intravenous injection of 3 mg technetium 99m diethylenetriaminepentaacetic acid-galactosyl human serum albumin. A total of 75 human subjects were studied: 6 controls without liver diseases, 51 patients with chronic liver diseases and 18 patients with acute liver diseases. In chronic liver disease the asialoglycoprotein receptor concentration significantly correlated with the clinical severity based on the criteria of the Liver Cancer Study Group of Japan (rs = -0.890, p = 0.0001). Good correlations between the asialoglycoprotein receptor concentration and conventional liver function tests were also observed. In acute liver disease the asialoglycoprotein receptor concentration correlated well with the normotest (r = 0.796, p = 0.0001), prothrombin time (r = 0.701, p = 0.0002) and total serum bilirubin (r = -0.642, p = 0.0007). We conclude that the parameter, asialoglycoprotein receptor concentration, obtained from the kinetic analysis of technetium 99m diethylenetriaminepentaacetic acid-galactosyl human serum albumin time-activity data, is a sensitive measure of functioning hepatocyte mass in acute and chronic liver disease.

Acute Disease↗
PubMed1992

Goodness-of-fit and local identifiability of a receptor-binding radiopharmacokinetic system.

A four-state nonlinear model describing a radiopharmacokinetic system for a hepatic receptor-binding radiopharmaceutical, [99mTc]-galactosyl-neoglycoalbumin (TcNGA), was tested for goodness-of-fit and local identifiability using scanning data from nine healthy subjects and seven patients with severe liver disease. Based on standard deviations of liver and heart imaging data at equilibria as a measure of observational error, the reduced chi-square ranged from 0.5 to 2.6. Values above 1.2 occurred when the subject moved during the 30 min study. Relative standard errors for each parameter were: TcNGA-receptor forward binding rate constant kb, 13-54%; extra-hepatic plasma volume Ve, 0.8-15.0%; hepatic plasma volume Vh, 0.2-6.5%; hepatic plasma flow F, 54----greater than 1000%; and receptor concentration [R]o, 0.3-13%. The highest standard errors occurred when the amount of TcNGA injected exceeded the total amount of receptor. Therefore, when TcNGA functional imaging was performed without excess patient motion and receptor saturation, the kinetic model provided data fits of low systematic error and yielded high precision estimates of receptor concentration and forward binding rate constant. In summary, optimal performance of the kinetic model occurred when the amount of injected TcNGA resulted in the nonlinear operation of the pharmacokinetic system.

Albumins↗
PubMed1991

Hepatic uptake of [99mTc]galactosyl-neoglycoalbumin is sensitive to receptor quantity.

[Technetium-99m]galactosyl-neoglycoalbumin (TcNGA) is a synthetic radioligand specific to the receptor, hepatic binding protein (HBP), which resides exclusively at the cell surface of hepatocytes. If the TcNGA time-activity data are to provide valid estimates of receptor biochemistry via pharmacokinetic modeling, the shape of the hepatic uptake curve must change with alterations in receptor concentration or affinity. An index of TcNGA hepatic uptake, T90, was obtained by calculating the time at which the liver time-activity curve reached 90% of its maximum. Receptor quantity was measured by Scatchard binding assay of liver biopsy samples obtained prior to each TcNGA study. The range of T90 was 3.7-16.8 min; HBP quantity ranged from 0.022 to 0.100 mumol. Significant correlation (r) and slope (b) was observed between T90 and HBP quantity (r = 0.82, P = 0.003; tb = 3.98, P = 0.003). We concluded that the hepatic uptake of TcNGA is sensitive to HBP quantity.

Adult↗
PubMed1991

[In vivo measurement of hepatic binding protein in chronic liver disease--validation as a measure of hepatic functional reserve].

[Tc-99m] Galactosyl-neoglycoalbumin (TcNGA) is a synthetic radiolabeled ligand specific to the hepatocyte receptor, hepatic binding protein (HBP), a specific receptor to serum asialoglycoprotein. A TcNGA study was performed on 34 humans: normal volunteers (7) chronic hepatitis (6), hepatic cirrhosis (8), and hepatocellular carcinoma superimposed on cirrhosis (13). Heart and liver time activity curves were obtained following intravenous injection of TcNGA (5 mCi, 1.82 x 10(-9) mol/kg). HBP concentration ([HBP]) was calculated by curve-fitting techniques using the nonlinear three compartment model, which includes biomolecular reaction between HBP and TcNGA. [HBP] values were compared with conventional liver function tests. [HBP] had a good correlation with prothrombin time (n = 34, r = 0.694, p = 0.0001) thrombotest (n = 34, r = 0.692, p = 0.0001), hepaplastin test (n = 26, r = 0.787, p = 0.0001), albumin (n = 34, r = 0.712, p = 0.0001), cholinesterase (n = 34, r = 0.801, p = 0.0001), ICGR15 (n = 33, r = 0.761, p = 0.0001), KICG (n = 30, r = 0.709, p = 0.0001), ICG Rmax (n = 12, r = 0.735, p = 0.0064) and Child-Turcotte classification score (n = 34, r = 0.819, p = 0.0001). We concluded that excellent correlations of [HBP] to conventional liver function tests suggest that in vivo receptor measurement via TcNGA kinetic analysis is a sensitive and promising method in the estimation of hepatic functional reserve in patients with chronic liver disease.

Adult↗
PubMed1991

Measurement of receptor concentration and forward-binding rate constant via radiopharmacokinetic modeling of technetium-99m-galactosyl-neoglycoalbumin.

Technetium-99m-galactosyl-neoglycoalbumin (99mTc-NGA) is a synthetic ligand to the hepatocyte receptor, hepatic binding protein (HBP). A five-state mathematical model containing a bimolecular chemical reaction was utilized for quantitative estimation of the following physiologic and biochemical parameters: extrahepatic plasma volume Ve; hepatic plasma flow F and volume Vh; receptor-ligand forward-binding rate constant kb and reaction volume Vr; and receptor concentration [R]o. Nine normal subjects were studied. Given (a) liver and heart time-activity data, (b) the patient's weight, height, and hematocrit, (c) the fraction of injected dose in a 3-min blood sample, and (d) the amount and galactose density of the NGA dose, a computer program executed a curve-fit to the kinetic model. Systematic error, as measured by reduced chi-square, ranged from 1.43 to 2.56. Based on the nine imaging studies, the mean and relative error of each parameter were: [R]o, 0.813 +/- (0.11) microM; kb, 2.25 +/- (0.15) microM-1 min-1; F, 0.896 +/- (0.20) liter/min; Ve, 1.67 +/- (0.27) liter; and Vh, 0.228 +/- (0.22) liter. Two unique features of 99mTc-NGA radiopharmacokinetic systems permit the simultaneous estimates of receptor quantity, ligand affinity, and hepatic plasma flow. The first is the ability to administer a quantity of ligand capable of occupying a significant fraction of receptor; and the second is a simple model structure that conserves mass.

Adult↗
PubMed1991

Validation of in vivo receptor measurements via in vitro radioassay: technetium-99m-galactosyl-neoglycoalbumin as prototype model.

Hepatic binding protein (HBP) is a hepatocyte-specific receptor for serum asialoglycoproteins. The receptor also recognizes a synthetic glycoprotein that has been developed as a radiopharmaceutical, technetium-99m-galactosyl-neoglycoalbumin (99mTc-NGA). This report describes the correlation between receptor parameters measured in vivo via kinetic modeling of 99mTc-NGA and those measured by in vitro radioassay of biopsied liver tissue. Eleven patients with diffuse hepatic disease underwent percutaneous liver biopsy followed by a 99mTc-NGA functional imaging study. In vivo measurements of HBP quantity Ro and forward binding rate constant kb obtained from the kinetic analysis of 99mTc-NGA liver and blood time-activity data were compared to total receptor quantity and the HBP-99mTc-NGA association constant KA as measured by Scatchard binding assay of the biopsied tissue. The correlation coefficients between in vivo and in vitro measurements were 0.73 (df = 8, p = 0.015) and 0.98 (df = 8, p less than 0.01) for Ro and kb, respectively. The in vivo measurements of HBP biochemistry via kinetic analysis of the radiopharmaceutical time-activity data reflect the average concentration and affinity of the receptor. This study further substantiates the validity of 99mTc-NGA as a quantitative probe for the HBP receptor.

Adult↗
PubMed1990

In vivo estimates of hepatic binding protein concentration: correlation with classical indicators of hepatic functional reserve.

Hepatic binding protein (HBP) is a hepatic cell surface receptor specific for asialoglycoprotein. In vivo estimates of HBP concentration ([HBP]) were compared to classical indicators for hepatic functional reserve to clarify the validity of [HBP] in estimating the hepatic functional reserve in 30 humans. Estimates of [HBP] were obtained based on kinetic analysis of liver and blood time-activity data resulting from the hepatic clearance of a single injection of technetium-99m galactosyl-neoglycoalbumin, which is a synthetic analog radioligand specific to HBP. Estimates of [HBP] ranged 0.054 to 0.720 microM. Estimates of [HBP] in normal volunteers were 0.668 +/- 0.050 microM, whereas that in liver cirrhosis were 0.188 +/- 0.112 microM. The difference between the mean values of [HBP] estimates was statistically significant (p = 0.0001). Good correlations were observed between [HBP] and prothrombin time (r = 0.625, p = 0.0002), serum albumin level (r = 0.687, p = 0.0001), serum cholinesterase level (r = 0.764, p = 0.0001), indocyanine green plasma disappearance rate (r = 0.602, p = 0.0024), and Child-Turcotte classification score (Pugh's modification) (r = -0.797, p = 0.0001). We concluded that excellent correlations of [HBP] with classical indicators for hepatic functional reserve suggest potential value of [HBP] as a sensitive measure of functioning hepatocyte mass.

Adult↗
PubMed1989

Kinetic sensitivity of a receptor-binding radiopharmaceutical: technetium-99m galactosyl-neoglycoalbumin.

Kinetic sensitivity is the ability of a physiochemical parameter to alter the time-activity curve of a radiotracer. The kinetic sensitivity of liver and blood time-activity data resulting from a single bolus injection of [99mTc]galactosyl-neoglycoalbumin [( Tc]NGA) into healthy pigs was examined. Three parameters, hepatic plasma flow scaled as flow per plasma volume, ligand-receptor affinity, and total receptor concentration, were tested using [Tc]NGA injections of various molar doses and affinities. Simultaneous measurements of plasma volume (iodine-125 human serum albumin dilution), and hepatic plasma flow (indocyanine green extraction) were performed during 12 [Tc]NGA studies. Paired data sets demonstrated differences (P(chi v2) less than 0.01) in liver and blood time-activity curves in response to changes in each of the tested parameters. We conclude that the [Tc]NGA radiopharmacokinetic system is therefore sensitive to hepatic plasma flow, ligand-receptor affinity, and receptor concentration. In vivo demonstration of kinetic sensitivity permits delineation of the physiologic parameters that determine the biodistribution of a radiopharmaceutical. This delineation is a prerequisite to a valid analytic assessment of receptor biochemistry via kinetic modeling.

Albumins↗
PubMed1989

Tc-NGA imaging in liver transplantation: preliminary clinical experience.

Technetium-99m galactosyl-neoglycoalbumin (Tc-NGA) is a new liver imaging agent that binds to hepatic-binding protein, a hepatocyte-specific membrane receptor. The purpose of this study was to determine the potential of Tc-NGA imaging in clinical liver transplantation. A total of 25 studies were performed in nine patients. Imaging studies performed in the early posttransplant period in patients with good hepatic allograft function revealed diffuse patchiness in tracer distribution, a manifestation of preservation damage. Left lobar infarction was demonstrated within a few hours of ischemic injury. Right posterior segmental infarction was seen in another patient. Comparison of kinetic, clinical, and biochemical data revealed good correlation between hepatic allograft function and Tc-NGA kinetics. Major kinetic alterations were noted during periods of preservation injury, hepatic infarction, and acute rejection. These studies indicate: (1) major alterations in Tc-NGA kinetics occur during preservation injury, hepatic infarction, and acute rejection, and (2) Tc-NGA kinetic data appear to provide an accurate reflection of hepatic allograft function. Tc-NGA imaging has the advantages of being noninvasive and of utilizing standard nuclear medicine instrumentation, including portable imaging devices. In conclusion, Tc-NGA imaging provides a promising noninvasive approach for evaluation of liver function in patients undergoing hepatic transplantation.

Adult↗