Effect of cholestasis on hepatic transport of /sup 99m/technetium p-isopropyl-iminodiacetic acid
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 from 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.
- Research Organization:
- Veterans Administration Medical Center, Minneapolis, MN
- OSTI ID:
- 6000381
- Journal Information:
- J. Lab. Clin. Med.; (United States), Vol. 104:4
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
BILIARY TRACT
RADIOISOTOPE SCANNING
JAUNDICE
DIAGNOSIS
LIVER
DYNAMIC FUNCTION STUDIES
ACETIC ACID
BILE
ESTRADIOL
ISOMERIC NUCLEI
PATIENTS
RATS
TECHNETIUM 99
TRACER TECHNIQUES
UPTAKE
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL MATERIALS
BODY
BODY FLUIDS
CARBOXYLIC ACIDS
COUNTING TECHNIQUES
DIGESTIVE SYSTEM
ESTRANES
ESTROGENS
GLANDS
HORMONES
HOURS LIVING RADIOISOTOPES
HYDROXY COMPOUNDS
INTERMEDIATE MASS NUCLEI
ISOMERIC TRANSITION ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
MAMMALS
MATERIALS
MONOCARBOXYLIC ACIDS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PATHOLOGICAL CHANGES
RADIOISOTOPES
RODENTS
STEROID HORMONES
STEROIDS
SYMPTOMS
TECHNETIUM ISOTOPES
VERTEBRATES
YEARS LIVING RADIOISOTOPES
550601* - Medicine- Unsealed Radionuclides in Diagnostics
551001 - Physiological Systems- Tracer Techniques