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Title: Quantitative temporal analysis of /sup 99m/Technetium p-isopropyl-iminodiacetic acid (PIPIDA) as a measure of hepatic function in health and disease

Abstract

Excretory liver function was analyzed in 10 healthy volunteers and 28 subjects with acute or chronic liver injury following intravenous administration of /sup 99m/technetium p-isopropyl iminodiacetic acid. Hepatobiliary transit of this agent was quantitated at 5-min intervals for a total of 60 min. Indices of total liver activity, liver cell uptake, liver parenchymal clearance, and bile duct clearance of /sup 99m/technetium p-isopropyl iminodiacetic acid were calculated from time--activity curves over heart, liver, extrahepatic bile ducts, and gallbladder. Seven subjects with acute viral hepatitis, 15 with extrahepatic biliary obstruction, and 6 with intrahepatic cholestasis were evaluated. Compared with healthy volunteers, a significant (p less than 0.0001) reduction in total liver activity and liver parenchymal clearance was demonstrated in all patient groups. Major resolution in all liver-derived indices, particularly total liver activity, occurred during convalescence from hepatitis and after biliary drainage. Nonmeasurable bile duct clearance always indicated a diagnosis of extrahepatic obstruction in cholestatic subjects, and this index normalized in subjects following biliary drainage. Whereas visual assessment of /sup 99m/technetium p-isopropyl iminodiacetic acid scans provided limited, useful information about the functional status of the liver, quantitative temporal analysis proved to be a much more effective technique.

Authors:
; ;
Publication Date:
Research Org.:
Veterans Administration Medical Center, St. Louis, Missouri
OSTI Identifier:
5547479
Resource Type:
Journal Article
Resource Relation:
Journal Name: Gastroenterology; (United States); Journal Volume: 81:6
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; 63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.; BILIARY TRACT; RADIONUCLIDE KINETICS; SCINTISCANNING; DIGESTIVE SYSTEM DISEASES; DIAGNOSIS; HEART; LIVER; TECHNETIUM 99; HEPATITIS; ISOMERIC NUCLEI; MAN; MONOCARBOXYLIC ACIDS; ORGANIC NITROGEN COMPOUNDS; ANIMALS; BETA DECAY RADIOISOTOPES; BETA-MINUS DECAY RADIOISOTOPES; BODY; CARBOXYLIC ACIDS; CARDIOVASCULAR SYSTEM; COUNTING TECHNIQUES; DIAGNOSTIC TECHNIQUES; DIGESTIVE SYSTEM; DISEASES; GLANDS; HOURS LIVING RADIOISOTOPES; INTERMEDIATE MASS NUCLEI; ISOMERIC TRANSITION ISOTOPES; ISOTOPES; MAMMALS; NUCLEI; ODD-EVEN NUCLEI; ORGANIC ACIDS; ORGANIC COMPOUNDS; ORGANS; PRIMATES; RADIOISOTOPE SCANNING; RADIOISOTOPES; TECHNETIUM ISOTOPES; VERTEBRATES; YEARS LIVING RADIOISOTOPES; 550601* - Medicine- Unsealed Radionuclides in Diagnostics; 560171 - Radiation Effects- Nuclide Kinetics & Toxicology- Man- (-1987)

Citation Formats

Joshi, S.N., George, E.A., and Perrillo, R.P.. Quantitative temporal analysis of /sup 99m/Technetium p-isopropyl-iminodiacetic acid (PIPIDA) as a measure of hepatic function in health and disease. United States: N. p., 1981. Web.
Joshi, S.N., George, E.A., & Perrillo, R.P.. Quantitative temporal analysis of /sup 99m/Technetium p-isopropyl-iminodiacetic acid (PIPIDA) as a measure of hepatic function in health and disease. United States.
Joshi, S.N., George, E.A., and Perrillo, R.P.. 1981. "Quantitative temporal analysis of /sup 99m/Technetium p-isopropyl-iminodiacetic acid (PIPIDA) as a measure of hepatic function in health and disease". United States. doi:.
@article{osti_5547479,
title = {Quantitative temporal analysis of /sup 99m/Technetium p-isopropyl-iminodiacetic acid (PIPIDA) as a measure of hepatic function in health and disease},
author = {Joshi, S.N. and George, E.A. and Perrillo, R.P.},
abstractNote = {Excretory liver function was analyzed in 10 healthy volunteers and 28 subjects with acute or chronic liver injury following intravenous administration of /sup 99m/technetium p-isopropyl iminodiacetic acid. Hepatobiliary transit of this agent was quantitated at 5-min intervals for a total of 60 min. Indices of total liver activity, liver cell uptake, liver parenchymal clearance, and bile duct clearance of /sup 99m/technetium p-isopropyl iminodiacetic acid were calculated from time--activity curves over heart, liver, extrahepatic bile ducts, and gallbladder. Seven subjects with acute viral hepatitis, 15 with extrahepatic biliary obstruction, and 6 with intrahepatic cholestasis were evaluated. Compared with healthy volunteers, a significant (p less than 0.0001) reduction in total liver activity and liver parenchymal clearance was demonstrated in all patient groups. Major resolution in all liver-derived indices, particularly total liver activity, occurred during convalescence from hepatitis and after biliary drainage. Nonmeasurable bile duct clearance always indicated a diagnosis of extrahepatic obstruction in cholestatic subjects, and this index normalized in subjects following biliary drainage. Whereas visual assessment of /sup 99m/technetium p-isopropyl iminodiacetic acid scans provided limited, useful information about the functional status of the liver, quantitative temporal analysis proved to be a much more effective technique.},
doi = {},
journal = {Gastroenterology; (United States)},
number = ,
volume = 81:6,
place = {United States},
year = 1981,
month = 1
}
  • Hepatobiliary imaging with /sup 99m/Tc-p-isopropyl-iminodiacetic acid (PIPIDA) and other acetanilidoiminodiacetic acid derivatives is a frequently used clinical tool in evaluating patients with jaundice. However, there has been little objective assessment of the effects of cholestasis on hepatic transport of acetanilioiminodiacetic acid derivatives. In our studies, transport of /sup 99m/Tc-PIPIDA by isolated rat hepatocytes obtained from animals with extrahepatic obstruction secondary to bile duct ligation or intrahepatic cholestasis induced by ethinyl estradiol therapy was determined. Uptake constants for /sup 99m/Tc-PIPIDA by hepatocytes isolated from livers of animals with ligated bile ducts were significantly decreased compared with uptake by liver cells frommore » sham-operated controls (0.0030 +/- 0.0003 vs. 0.0089 +/- 0.0010 femtomole X 10(6) cells-1 X min-1 X pmol/L-1; p less than 0.001). Hepatocytes isolated from livers of animals given ethinyl estradiol also demonstrated significantly reduced /sup 99m/Tc-PIPIDA uptake compared with controls given propylene glycol (0.0034 +/- 0.0002 vs. 0.0060 +/- 0.0004 fmol X 10(6) cells-1 X min-1 X pmol/L-1; p less than 0.001). Fractional rates of efflux of the study compound from hepatocytes preincubated with /sup 99m/Tc-PIPIDA were significantly decreased in experiments using ethinyl estradiol (p less than 0.005) but did not differ significantly from controls in studies of bile duct ligation. /sup 99m/Tc-PIPIDA uptake was significantly decreased in the presence of high bile salt concentrations (100 to 200 mumol/L), but unconjugated bilirubin concentrations as high as 200 mumol/L (approximately 12 mg/dl) had no effect on hepatocyte uptake of the ligand.« less
  • Parameters affecting the hepatobiliary clearance of /sup 99m/Tc N(2,6-dimethylphenylcarbamoylmethyl) iminodiacetic acid (Tc-HIDA) were evaluated in dogs. Competitive clearance studies were performed with Tc-HIDA after infusion to plasma saturation levels of an anion, sodium sulfobromophthalein (BSP), and a cation, oxyphenonium. The results demonstrated that Tc-HIDA is transported through hepatocytes by a carrier-mediated organic-anion pathway. The data are consistent with an alteration of the elimination kinetics of Tc-HIDA induced by elevations in the serum bilirubin level, and it is predicted that serum bilirubin at some increased concentration will dominate the distribution and elimination kinetics of Tc-HIDA independently of hepatobiliary status. A quantitativemore » description of liver function in terms of regional distribution and elimination rate constants will require either a pharmacokinetic model that expressly includes the effects of bilirubin from transport binding sites, or the development of new hepatobiliary agents that use a different clearance mechanism from that used by bilirubin.« less
  • The purpose of this study was to determine whether /sup 99m/Tc-iminodiacetic acid planar biliary scintigraphy combined with single photon emission computed tomography could detect sclerosing cholangitis and provide additional information regarding the extent and severity of disease. Thirteen patients with sclerosing cholangitis and 13 normal control subjects were studied. Scintigraphic results were also compared with previously reported studies of patients with isolated common bile duct obstruction and with primary biliary cirrhosis. The planar scintigraphy in patients with sclerosing cholangitis showed beading or bandlike constrictions of the biliary tract corresponding to lesions seen on cholangiography, and the image pattern was distinctlymore » different from images obtained from patients with isolated common bile duct obstruction or primary biliary cirrhosis. The single photon emission computed tomography images of the liver in patients with sclerosing cholangitis demonstrated multiple focal areas of /sup 99m/Tc-iminodiacetic acid retention, representing bile stasis in intrahepatic bile ducts. Compared to controls, the mean hepatic clearance half-time of /sup 99m/Tc-iminodiacetic acid was markedly delayed in patients with sclerosing cholangitis (6-10 times normal). Individual patients with sclerosing cholangitis had wider variation in isotope clearance half-time from three regions of the liver than patients with isolated common bile duct obstruction, consistent with regional difference in disease severity and variable impairment of bile flow. In 4 patients with sclerosing cholangitis with incomplete filling of the right and left hepatic ducts at cholangiography, planar and single photon emission computed tomographic scintigraphy provided evidence of significant intrahepatic sclerosing cholangitis.« less
  • Forty-one proved cases of acute acalculous cholecystitis imaged with technetium-99m iminodiacetic acid (IDA) cholescintigraphy were retrospectively analyzed. After the exclusion of one indeterminate scan (showing poor initial hepatic uptake and excretion), the study yielded a 92.5% (37 of 40) sensitivity for the detection of cystic or common bile duct obstruction. Each of the three patients with false-negative scintigrams had other abnormal scintigraphic findings suggestive of biliary tract disease. Of the 20 patients (48.8%) with focal or diffuse gangrenous cholecystitis or perforation, seven (35%) exhibited either free peritoneal spill or increased pericholecystic activity to indicate the presence of advanced disease.
  • An easily formulated, stable kit preparation of technetium-99m HIDA, suitable for use in humans, was developed and tested in mice and dogs. The tracer was cleared rapidly from the blood and excreted predominantly by the liver in both species. In dogs, the hepatobiliary clearance of Tc-99m HIDA was significantly greater than that of C-14 HIDA and Sn-113 HIDA. The LD/sub 50/ for HIDA in mice, 168 mg/kg, exceeded the average human dose by a factor of 1000 on a per-weight basis. Blood clearance curves for Tc-99m HIDA in 12 normal subjects were biexponential with half-times of 4.6 +- 1.0 minmore » and 31.5 +- 7.0 min, and cumulative 90-min urine samples contained 14.2 +- 1.8% of the injected dose. Images in normal subjects and nonjaundiced patients showed rapid concentration of tracer by the liver and activity was present within the biliary system in 10 to 20 min. In jaundiced patients, the tracer blood clearance was delayed and urinary excretion increased, but intestinal activity, indicating biliary patency, was imaged in those patients without complete focal obstruction of the common duct. Technetium-99m HIDA is a nontoxic radiopharmaceutical useful for clinical evaluation of hepatobiliary disorders in humans.« less