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R C Stadalnik

Publications and source records attributed to R C Stadalnik.

At least 19 recordsLinked to original sources
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↗
PubMed1987

Functional causes of the ductal obstructive pattern on hepatobiliary scans.

Hepatobiliary imaging with Tc-99m IDA derivatives has proven value for evaluation of biliary disease. Prompt hepatocellular uptake with persistent nonvisualization of the common bile duct and bowel is usually indicative of a high-grade common bile duct obstruction, but is not pathognomonic. A functional abnormality due to hepatocyte dysfunction resulting in intrahepatic cholestasis can also cause this pattern. Two cases of hepatocellular excretory dysfunction, one due to E. coli endotoxemia with intrahepatic cholestasis and the other due to acute hepatitis A that produces ductal obstructive patterns on Tc-99m disofenin scintigraphy in patients with documented patent biliary ducts, are reported. Transhepatic cholangiography or endoscopic retrograde cholangiography may be useful when the diagnosis of biliary ductal obstruction is in doubt.

Adult↗
PubMed1987

Tc-NGA imaging in liver transplantation: preclinical studies.

Tc-99m galactosyl-neoglycoalbumin (Tc-NGA) is a new liver-imaging agent which binds to hepatic binding protein (an hepatocyte-specific membrane receptor). This study evaluated the sensitivity of Tc-NGA kinetics and imaging anatomy to pathologic states that are encountered after liver transplantation. Studies were performed in adolescent pigs under control conditions (18 studies), and after orthotopic liver transplantation (nine studies), common bile duct ligation (three studies), hepatic artery ligation (one study), and hepatic resection (two studies). Anatomic and kinetic data were analyzed. Excellent liver images and minimal kinetic changes were noted after common bile duct ligation. Marked imaging defects and major kinetic alterations were observed after hepatic artery ligation and in the presence of preservation injury. Marked depression in hepatic Tc-NGA uptake was observed during acute rejection. Minor alterations in Tc-NGA kinetics were noted after a 25% hepatectomy. These studies indicate that minimal changes in Tc-NGA uptake occur after common bile duct ligation; Tc-NGA uptake is markedly sensitive to hepatic ischemia; decreased Tc-NGA uptake occurs during acute rejection; and hepatic infarcts are demonstrated promptly after preservation injury. Thus Tc-NGA imaging provides a novel means of evaluating hepatic ischemia, hepatic preservation, and hepatic allograft rejection. Tc-NGA imaging may also provide a means of evaluating hepatic regeneration and hepatocyte retrodifferentiation during regeneration.

Albumins↗
PubMed1985

Technetium-99m NGA functional hepatic imaging: preliminary clinical experience.

Technetium-99m galactosyl-neoglycoalbumin ( [Tc]NGA) is a radiolabeled ligand to hepatic binding protein, a receptor which resides at the plasma membrane of hepatocytes. This receptor-binding radiopharmaceutical and its kinetic model provide a noninvasive method for the assessment of liver function. Eighteen patients were studied: seven with hepatoma, eight with liver metastases, four with cirrhosis (two had concurrent hepatoma and one chronic active hepatitis), and one patient with acute fulminant non-A, non-B hepatitis. Technetium-99m NGA liver imaging provided anatomic information of diagnostic quality comparable to that obtained with other routine imaging modalities, including computed tomography, angiography, ultrasound, and [Tc]sulfur colloid scintigraphy. Kinetic modeling of dynamic [Tc]NGA data produced estimates of standardized hepatic blood flow, Q (hepatic blood flow divided by total blood volume), and hepatic binding protein concentration, [HBP]. Clinical correlation was by classical Child-Turcotte criteria (CTC). Significant rank correlation was obtained between [HBP] estimates and CTC scores (rs = -0.72, p = 0.001). This correlation supports the hypothesis that [HBP] is a measure of functional hepatocyte mass. The combination of decreased Q and markedly reduced [HBP] may have prognostic significance; all three patients with this combination died of hepatic failure within 6 wk of imaging.

Adult↗
PubMed1978

Biodistribution studies of labeled tryptophan: a potential pancreas-scanning agent.

The in vivo organ distributions of dl- and l-[side 3-14C]-tryptophan and dl-(75Se)-selenomethionine were studied in normal Long-Evans rats to determine which tryptophan isomer had the best pancreas/liver ratio. The commercially available radiochemical agents were injected into the tails of adult rats, and three animals were sacrificed for each compound at 15, 30, 45, 60, and 90 minutes. Samples of blood, pancreas, liver, kidney, spleen, and flank muscles were excised, weighed wet, digested, and counted by standard liquid scintillation technics. A standard fraction of the injected dose was also counted so that results could be reported as per cent injected dose per gram tissue (per cent ID/gm) and per whole organ. The spleen and muscle concentrations (per cent ID/gm) were indistinguishable for the three compounds at all times studied. The kidney concentration of dl-tryptophan was higher than that of l-tryptophan at 60 and 90 minutes, reflecting the renal excretion of the nonmetabolic isomer. The concentration of l-tryptophan was two to three times higher than that of dl-tryptophan and selenomethionine in the pancreas at the earlier times, but after 1 hour they became equivalent. All three compounds had equivalent concentrations in the liver, except for l-tryptophan at 15 minutes. We conclude that pancreas/liver ratios are much higher for tryptophan than for selenomethionine and that for l-tryptophan they are at least tenfold higher. Since the rat is able to partially metabolize d-tryptophan via an inversion step, differences between l- and dl-tryptophan might be even larger for humans. L-tryptophan labeled with a short-lived gamma-emitting nuclide (13N or 11C) should, therefore, be a much better radiopharmaceutical agent for pancreatic scintigraphy.

Animals↗
PubMed1978

Definitive diagnosis of choledochal cyst by 99mTc-pyridoxylideneglutamate sequential scintiphotography.

Sequential supine scintiphotography of the abdomen was performed after intravenous administration of 99mTc-pyridoxylideneglutamate (99mTc-PG) to verify the presence of choledochal cyst in an 18-month-old boy who presented with a mass in the right upper quadrant of the abdomen. The total body radioactivity effect, which is similar to the total body opacification during intravenous cholangiography or urography, was clearly demonstrated as a cold area corresponding to the cyst and assisted in the diagnosis. The specific finding was sequential filling of the gallbladder and cyst. In view of the relatively low radiation dose and good physical characteristics of 99mTc for imaging, 99mTc-PG sequential scintiphotography is useful for the definitive preoperative diagnosis of choledochal cyst in infants and children.

Biliary Tract Diseases↗