Summary
Asialoglycoprotein receptor (ASGP-R) is a hepatic cell surface receptor specific for galactose-terminated glycoproteins. Technetium-99m diethylenetriaminepentaacetic acid-galactosyl human serum albumin (TcGSA) is a newly developed analog ligand to ASGP-R. Fourteen human subjects were studied: three normal volunteers, one with chronic hepatitis, 6 with liver cirrhosis, and 4 with hepatocellular carcinoma associated with liver cirrhosis. The receptor index parameter (LHL15), was obtained from the liver and heart time-activity data as the ratio of radioactivity of the liver over that of the liver plus heart at 15 min after intravenous injection of 1 mg of TcGSA. Means±standard deviations of LHL15 in normal volunteers (3 cases), patients with mild (4 cases), moderate (2 cases), and severe liver damage (5 cases) were 0.933±0.006, 0.789±0.045, 0.723±0.033, and 0.488±0.094, respectively. The difference between the mean values of each group was statistically significant (P<0.05). LHL15 correlated well with classical indicators for hepatic functional capacity such as serum albumin level, serum bilirubin level, prothrombin time, ICG R15 or Child-Turcotte criteria score. Our preliminary experiences of high correlations of TcGSA functional imaging data with clinical data suggest that the dynamic data using this receptor-binding radiopharmaceutical provides invaluable information with regard to liver function, and thus, the TcGSA study is potentially a noninvasive practical tool to measure functioning hepatocyte mass.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Morell AG, Irvine RA, Sternlieb I, et al: Physical and chemical studies on ceruloplasmin. V. Metabolic studies on sialic acid free ceruloplasmin in vivo. J Biol Chem 1968;243:155–159.
Ashwell G, Steer CJ: Hepatic recognition and catabolism of serum glycoproteins. JAMA 1981;246:2358–2364.
Stocken RJ, Morell AG: Hepatic binding protein. The galactosespecific receptor of mammalian hepatocytes. Hepatology 1983;3: 750–757.
Lee YC, Stowell CP, Krantz MJ: 2-Imino-2-methoxyethy-1 -thioglycosides: new reagents for attaching sugars to proteins. Biochem 1976; 15:3956–3963.
Vera DR, Stadalnik RC, Krohn KA: Technetium-99m galactosylneoglycoalbumin: preparation and preclinical studies. J Nucl Med 1985;26:1157–1167.
Eckelman WC, Reba RC, Gibson RE, et al: Receptor-binding radiotracers: a class of potential radiopharmaceuticals. J Nucl Med 1979;20:350–357.
Krohn KA, Vera DR, Stadalnik RC: A complementary radi pharmaceutical model for quantitating hepatic-binding protein receptors. In: Eckelman WC, Colombetti LG, eds. Receptor-Binding Radiotracers II CRC Press, Boca Raton 1982;41–59.
Vera DR, Krohn KA, Stadalnik RC, et al: Tc-99m-galactosyl-neoglycoalbumin: in vivo characterization of receptor-mediated binding to hepatocytes. Radiology 1984; 151:191 -196.
Stadalnik RC, Vera DR, Woodle S, et al: Technetium-99m NGA functional hepatic imaging: preliminary clinical experience. J Nucl Med 1985;26:1233–1242.
Bossuyt A, DE Geeter F, Jacobs A, et al: Initial clinical experience with a new kit formulation of Tc-99m-ß galactosylated albumin for functional hepatic imaging. Nucl Med Com 1990; 11:469–475.
Kudo M, Todo A, Ikekubo K, et al: Evaluation of asialoglycoprotein receptor-binding, synthetic radiolabeled glycoprotein in estimating hepatic functional reserve. Acta Hepat Jap 1987;28:1277–1286. (in Japanese)
Liver Cancer Study Group of Japan: The general rules for the clinical and pathological study of primary liver cancer. 2nd ed. Kanehara Publishing Co., Tokyo. 1987;23. (in Japanese)
Schlichting P, Christensen E, Andersen PK, et al: Prognostic factors in cirrhosis identified by Cox’s regression model. Hepatology 1983;3: 889–895.
Christensen E, Schlichting P, Andersen PK, et al: Updating prognosis and therapeutic effect evaluation in cirrhosis with Cox’s multiple regression model for time-dependent variables. Scand J Gastroenterol 1986;21:163–174.
Orrego H, Israel Y, Blake JE, et al: Assessment of prognostic factors in alcoholic liver disease: toward a global quantitative expression of severity. Hepatology 1983;3:896–905.
Christensen E, Schlichting P, Fauerholdt L, et al: Prognostic value of Child-Turcotte criteria in medically treated cirrhosis. Hepatology 1984;4:430–435.
Infante-Rivard C, Esnaola S, Villeneuve JP: Clinical and statistical validity of conventional prognostic factors in predicting short-term survival among cirrhotics. Hepatology 1987;7:660–664.
Nambu M, Kobayashi N, Yamashiro Y, et al: Indocyanine green test and prognosis of the hepatic disease. Jpn J Gastroenterol 1978;75: 198–204. (in Japanese)
Pugh RNH, Murray-Lyon IM, Dawson JL, et al: Transection of the esophagus for bleeding esophageal varices. Br J Surg 1973;60:646–649.
Vera DR, Krohn KA, Scheibe PO, et al: Identifiability analysis of anin vivo receptor-binding radiopharmacokinetic system. IEEE Trans Biomed Eng 1985;BME-32:312–322.
Kudo M, Vera DR, Stadalnik RC et al: In vivo estimates of hepatic binding protein concentration: correlation with classical indicators of hepatic functional reserve. Am J Gastroenterol 1990;85:1142–1148.
Kudo M, Vera DR, Stadalnik RC et al: In vivo measurement of hepatic binding protein in chronic liver disease: validation as a measure of hepatic functional reserve. Jpn J Gastroenterol 1991;88:40–50. (in Japanese)
Vera DR, Stadalnik RC, Trudeau WL, et al: Measurement of receptor concentration and forward binding rate constant via radiopharmacokinetic modeling of technetium-99m-galactosyl-neoglycoalbumin. J Nucl Med 1991;32:1169–1176.
Kudo M, Todo A, Ikekubo K, et al: Estimation of hepatic functional reserve by asialoglycoprotein receptor-binding, radiolabeled synthetic ligand “Tc-99m-galactosyl-neoglycoalbumin”: preclinical and clinical studies. Jap J Nucl Med 1987;24:1653–1662. (in Japanese)
Pricer WE Jr. Ashwell G: Subcellular distribution of a mammalian hepatic binding protein specific for asialoglycoproteins. J Biol Chem 1976;251:7539–7544.
Stockert RJ, Howard DJ, Morell AG, et al: Functional segregation of hepatic receptors for asialoglycoproteins during endocytosis. J Biol Chem 1980;225:9028–9029.
Gartner U, Stockert RJ, Morell AG, et al: Modulation of the transport of bilirubin and asialoorosomucoid during liver regeneration. Hepatology 1981;1:99–106.
Wood AJJ, Villeneuve JP, Brance RA, et al: Intact hepatocyte theory of impaired drug metabolism in experimental cirrhosis in the rat. Gastroenterology 1979;76:1358–1362.
Kilbourn MR, Zalutsky MR: Research and clinical potential of receptor based radiopharmaceuticals. J Nucl Med 1985;26:655–662.
Stadalnik RC, Vera DR, Krohn KA: Receptor-binding radiopharmaceuticals: experimental and clinical aspects. In: Freeman LM, Wessmann HS, Eds. nuclear medicine annual 1986; 105–139.
Vera DR, Krohn KA, Stadalnik RC, et al: Tc-99m-galactosyl-neoglycoalbumin: in vitro characterization of receptor-mediated binding. J Nucl Med 1984;25:779–787.
Kudo M, Vera DR, Trudeau WL, et al: Validation of in vivo receptor measurements via in vitro radioassay: technetium-99m-galactysylneoglycoablumin as a prototype model. J Nucl Med 1991;32:1177–1182.
Author information
Authors and Affiliations
Additional information
This study was supported in part by a grant from the Grant-in-Aid for Medical Research of Kobe City General Hospital.
Rights and permissions
About this article
Cite this article
Kudo, M., Todo, A., Ikekubo, K. et al. Functional hepatic imaging with receptor-binding radiopharmaceutical: Clinical potential as a measure of functioning hepatocyte mass. Gastroenterol Jpn 26, 734–741 (1991). https://doi.org/10.1007/BF02782861
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02782861