HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Miki, K. Articles by Makuuchi, M. Search for Related Content PubMed PubMed Citation Articles by Miki, K. Articles by Makuuchi, M.

Asialoglycoprotein Receptor and Hepatic Blood Flow Using Technetium-99m-DTPA-Galactosyl Human Serum Albumin

Second Department of Surgery and Department of Radiology, Faculty of Medicine, University of Tokyo; Department of Surgery, Cancer Institute Hospital; and Department of Surgery, Central Hospital of Social Health Insurance, Tokyo, Japan

Correspondence: For correspondence or reprints contact: Kenji Miki, MD, Second Department of Surgery, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo 113, Japan.

ABSTRACT

Asialoglycoprotein receptor (ASGP-R) amount and hepatic blood flow were quantitatively measured by using a newly developed kinetic model of ^99mTc-labe1ed 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 wfth 10 parameters as variables. To estimate total receptor amount (R_total), hepatic plasma flow (Q) and hepatic plasma volume (V_total), 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 R_total, 0 and V_h. Results: The values of the fixed parameters were estimated as follows: dissociation constant, 0.032 µM; 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 R_total 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 R_total values, but not in their Q or V_h values. The s.e. values of R_total, Q and V_total for normal livers were small, and the s.e. values of Q and V_total were high for cirrhotic livers. Conclusion: 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.

Key Words: technetium-99m-GSA • pharmacokinetics • asialoglycoprotein receptor • receptor-mediated endocytosis • receptor recycling

This article has been cited by other articles:

				W. de Graaf, R. L. Vetelainen, K. de Bruin, A. K. van Vliet, T. M. van Gulik, and R. J. Bennink 99mTc-GSA Scintigraphy with SPECT for Assessment of Hepatic Function and Functional Volume During Liver Regeneration in a Rat Model of Partial Hepatectomy J. Nucl. Med., January 1, 2008; 49(1): 122 - 128. [Abstract] [Full Text] [PDF]

				N. Shuke, A. Okizaki, S. Kino, J. Sato, Y. Ishikawa, C. Zhao, S. Kinuya, N. Watanabe, K. Yokoyama, and T. Aburano Functional Mapping of Regional Liver Asialoglycoprotein Receptor Amount from Single Blood Sample and SPECT J. Nucl. Med., March 1, 2003; 44(3): 475 - 482. [Abstract] [Full Text] [PDF]

				K. Miki, K. Kubota, Y. Inoue, D. R. Vera, and M. Makuuchi Receptor Measurements via Tc-GSA Kinetic Modeling Are Proportional to Functional Hepatocellular Mass J. Nucl. Med., May 1, 2001; 42(5): 733 - 737. [Abstract] [Full Text]