Asialoglycoprotein receptor and hepatic blood flow using technetium-99m-DTPA-galactosyl human serum albumin.
Asialoglycoprotein receptor (ASGP-R) amount and hepatic blood flow were quantitatively measured by using a newly developed kinetic model of 99mTc-labeled diethylenetriaminepentaacetic acid-galactosyl human serum albumin (99mTc-GSA) in which receptor-mediated endocytosis and receptor recycling were considered.


METHODS
Five healthy volunteers were intravenously injected 3-mg and 9-mg 99mTc-GSA doses. The absolute amounts of 99mTc-GSA in the liver and extrahepatic blood were estimated from the time-activity curves for the liver, heart and lung. The metabolic process was represented by five differential equations with 10 parameters as variables. To estimate total receptor amount (Rtotal), hepatic plasma flow (Q) and hepatic plasma volume (Vh), other parameters were fixed and estimated by analyzing their data with the least-squares method. Nineteen patients with liver diseases were given a 3-mg dose, and the data were analyzed to estimate Rtotal, Q and Vh.


RESULTS
The values of the fixed parameters were estimated as follows: dissociation constant, 0.032 microM; rate constant for internalization, 0.604 min(-1); and ratio of surface receptors to total receptors, 6.1%. The fitted liver uptake curve corresponded well to the measured data. The simulated liver uptake curve was significantly influenced by Rtotal and Q in cases with normal receptor amounts. Analysis in patients with normal livers, chronic hepatitis and liver cirrhosis showed statistically significant differences in their Rtotal values, but not in their Q or Vh values. The s.e. values of Rtotal, Q and Vh for normal livers were small, and the s.e. values of Q and Vh were high for cirrhotic livers.


CONCLUSIONS
This method is useful for measuring ASGP-R amount and hepatic blood flow simultaneously based on dynamic images, without the need for blood sampling, and reflects the cellular transport of asialoglycoproteins and the ASGP-R recycling mechanism.
Miki
K
K
Second Department of Surgery, Faculty of Medicine, University of Tokyo, Japan.
Kubota
K
K
Kokudo
N
N
Inoue
Y
Y
Bandai
Y
Y
Makuuchi
M
M
D000328:Adult; D000368:Aged; D037263:Asialoglycoprotein Receptor; D001212:Asialoglycoproteins / Q000032:analysis / Q000378:metabolism; D016022:Case-Control Studies; D004705:Endocytosis; D005260:Female; D006801:Humans; D008099:Liver / Q000000981:diagnostic imaging* / Q000378:metabolism; D008102:Liver Circulation / Q000502:physiology*; D008107:Liver Diseases / Q000000981:diagnostic imaging* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D011956:Receptors, Cell Surface / Q000032:analysis* / Q000378:metabolism; D013668:Technetium Tc 99m Aggregated Albumin; D016284:Technetium Tc 99m Pentetate
D037263:Asialoglycoprotein Receptor; D001212:Asialoglycoproteins; D019275:Radiopharmaceuticals; D011956:Receptors, Cell Surface; D013668:Technetium Tc 99m Aggregated Albumin; C070561:technetium Tc 99m DTPA-galactosyl-human serum albumin; D016284:Technetium Tc 99m Pentetate