Background & Aims
The asialoglycoprotein receptor on hepatocyte membranes recognizes the galactose residues of glycoproteins. We investigated the specificity, accuracy and threshold value of asialoglycoprotein receptor imaging for estimating liver reserve via scintigraphy using 111In-hexavalent lactoside in mouse models.
111In-hexavalent lactoside scintigraphy for asialoglycoprotein receptor imaging was performed on groups of normal mice, orthotopic SK-HEP-1-bearing mice, subcutaneous HepG2-bearing mice, mice with 20–80% partial hepatectomy and mice with acute hepatitis induced by acetaminophen. Liver reserve was measured by relative liver uptake and compared with normal mice. Asialoglycoprotein receptor blockade was performed via an in vivo asialofetuin competitive binding assay.
A total of 73.64 ± 7.11% of the injection dose accumulated in the normal liver tissue region, and radioactivity was barely detected in the hepatoma region. When asialoglycoprotein receptor was blocked using asialofetuin, less than 0.41 ± 0.04% of the injection dose was detected as background in the liver. Asialoglycoprotein receptor imaging data revealed a linear correlation between 111In-hexavalent lactoside binding and residual liver mass (R2 = 0.8548) in 20–80% of partially hepatectomized mice, demonstrating the accuracy of 111In-hexavalent lactoside imaging for measuring the functional liver mass. Asialoglycoprotein receptor imaging data in mice with liver failure induced using 600 mg/kg acetaminophen revealed 19–45% liver reserve relative to normal mice and a fatal threshold value of 25% liver reserve.
The 111In-hexavalent lactoside imaging method appears to be a good, specific, visual and quantitative predictor of functional liver reserve. The diagnostic threshold for survival was at 25% liver reserve in mice.
Abbreviations:ASGPR (Asialoglycoprotein receptor), HL (Hexavalent lactoside), ICG15 (Indocyanine green clearance test), ICG (Indocyanine green), GalNAc (N-acetylgalactosamine), DTPA (Diethylene triamine pentaacetic acid), GSA (Galactosyl-human serum albumin), NGA (Neogalactosylalbumin), NOD-SCID (Non-obese diabetic-severe combined immunodeficiency), SPF (Specific pathogen-free), ATCC (American type culture collection), AST (Aspartate aminotransferase), INER (Institute of Nuclear Energy Research), NTA (Nitrile triacetic acid), ITLC (Instant thin layer chromatography), SG (Silica gel), Rf (Retention factor), SPECT (Single photon emission computer tomography), CT (Computed tomography), ROI (Region of interest), %ID (Percent of injection dose), PHx (Partial hepatectomy), APACHE II (Acute Physiology and Chronic Health Evaluation), MELD (Models of End-Stage Liver Disease), CMC (carboxymethyl cellulose)
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- Chronic viral hepatitis as a public health issue in the world.Best Pract Res Clin Gastroenterol. 2008; 22: 991-1008
- Entecavir vs. lamivudine in chronic hepatitis B patients with severe acute exacerbation and hepatic decompensation.J Hepatol. 2014; 60: 1127-1134
- How much liver resection is too much?.Am J Surg. 2005; 190: 87-97
- Usefulness of Tc-99m-GSA scintigraphy for liver surgery.Ann Nucl Med. 2011; 25: 593-602
- Measuring hepatic functional reserve using low temporal resolution Gd-EOB-DTPA dynamic contrast-enhanced MRI: a preliminary study comparing galactosyl human serum albumin scintigraphy with indocyanine green retention.Eur Radiol. 2014; 24: 112-119
- Evaluation of preoperative hepatic function in patients with hepatocellular carcinoma undergoing hepatectomy.Br J Surg. 1997; 84: 1255-1259
- Reliability of the estimation of total hepatic blood flow by Doppler ultrasound in patients with cirrhotic portal hypertension.J Hepatol. 2013; 59: 717-722
- Preoperative assessment of liver function.Surg Clin North Am. 2004; 84: 355-373
- Nuclear imaging techniques for the assessment of hepatic function in liver surgery and transplantation.J Nucl Med. 2010; 51: 742-752
- Major hepatectomy for hepatocellular carcinoma in patients with an unsatisfactory indocyanine green clearance test.Br J Surg. 1999; 86: 1012-1017
- Effect of preoperative portal vein embolization on major hepatectomy for advanced-stage hepatocellular carcinomas in injured livers: a preliminary report.Surg Today. 1997; 27: 403-410
- Estimation of the functional reserve of human liver.Ann Surg. 1974; 180: 592-598
- Indocyanine green: observations on its physical properties, plasma decay, and hepatic extraction.J Clin Invest. 1960; 39: 592-600
- The role of surface carbohydrates in the hepatic recognition and transport of circulating glycoproteins.Adv Enzymol Relat Areas Mol Biol. 1974; 41: 99-128
- Physical and chemical studies on ceruloplasmin. V. Metabolic studies on sialic acid-free ceruloplasmin in vivo.J Biol Chem. 1968; 243: 155-159
- Neoglycoproteins as probes for binding and cellular uptake of glycoconjugates.in: The Glycoconjugates. Academic Press, New York1982: 57-83
- New synthetic cluster ligands for galactose/N-acetylgalactosamine-specific lectin of mammalian liver.Biochemistry. 1984; 23: 4255-4261
- A quantitative model of technetium-99m-DTPA-galactosyl-HSA for the assessment of hepatic blood flow and hepatic binding receptor.J Nucl Med. 1991; 32: 2233-2240
- Synthesis and biological evaluation of (99m)Tc-DMP-NGA as a novel hepatic asialoglycoprotein receptor imaging agent.Appl Radiat Isot. 2010; 68: 105-109
- New and more efficient multivalent glyco-ligands for asialoglycoprotein receptor of mammalian hepatocytes.Bioorg Med Chem. 2011; 19: 2494-2500
- Labelling of Peptide Derivative with In-111 for Receptor Imaging.J Label Compd Radiopharm. 2010; 53: 406-489
- Experimental pathology of the liver-restoration of the liver of the white rat following partial surgical removal.Arch Pathol. 1931; 12: 186-202
- A reproducible and well-tolerated method for 2/3 partial hepatectomy in mice.Nat Protoc. 2008; 3: 1167-1170
- Addendum: a reproducible and well-tolerated method for 2/3 partial hepatectomy in mice.Nat Protoc. 2014; 9
- Liver-receptor imaging injection, dispensing method and pharmaceutical composition thereof. TWI392511.Institute of Nuclear Energy Research, Taiwan2013
- Asialoglycoprotein receptor-targeted radiopharmaceuticals for measurement of liver function.Curr Med Chem. 2014; 21: 4-23
- Liver function testing with nuclear medicine techniques is coming of age.Semin Nucl Med. 2012; 42: 124-137
- Chapter 8 Liver disease. Lecture notes on clinical biochemistry.5th ed. Blackwell Scientific Publications, 1993 (p. 105)
Washino K, Kurami M. Radioactive matallic element-labelled high molecular compound useful in nuclear medicine. US 5118792; 1992.
- Hyperasialoglycoproteinemia in patients with chronic liver diseases and/or liver cell carcinoma. Asialoglycoprotein receptor in cirrhosis and liver cell carcinoma.Gastroenterology. 1984; 87: 1217-1221
- Liver asialoglycoprotein receptor levels correlate with severity of alcoholic liver damage in rats.J Appl Physiol. 2004; 96: 76-80
- Asialoglycoprotein receptor concentration in tumor-bearing livers and its fate early after their sectorial resection.Ann Nucl Med. 2003; 17: 489-493
- Targeted delivery of macromolecular drugs: asialoglycoprotein receptor (ASGPR) expression by selected hepatoma cell lines used in antiviral drug development.Curr Drug Deliv. 2008; 5: 299-302
- A membrane receptor protein for asialoglycoproteins.Methods Enzymol. 1974; 34: 688-691
- A novel and efficient liver targeting agent: biodistribution, pharmacokinetics, SPECT/CT imaging, and autoradiography.Eur J Nucl Med Mol Imaging. 2009; 36: S470
- Early indicators of prognosis in fulminant hepatic failure.Gastroenterology. 1989; 97: 439-445
- Early indicators of prognosis in fulminant hepatic failure: an assessment of the King’s criteria.J Hepatol. 1997; 26: 62-68
- Multivariate analysis of prognostic factors in fulminant hepatitis B.Hepatology. 1986; 6: 648-651
- APACHE-acute physiology and chronic health evaluation: a physiologically based classification system.Crit Care Med. 1981; 9: 591-597
- APACHE II score is superior to SOFA, CTP and MELD in predicting the short-term mortality in patients with acute-on-chronic liver failure (ACLF).J Dig Dis. 2013; 14: 484-490
- A model to predict poor survival in patients undergoing transjugular intrahepatic portosystemic shunts.Hepatology. 2000; 31: 864-871
- A novel integrated Model for End-Stage Liver Disease model predicts short-term prognosis of hepatitis B virus-related acute-on-chronic liver failure patients.Hepatol Res. 2014;
- Timing and benefit of liver transplantation in acute liver failure.J Hepatol. 2014; 60: 663-670
- Early indicators of prognosis in fulminant hepatic failure: an assessment of the Model for End-Stage Liver Disease (MELD) and King’s College Hospital criteria.Liver Transpl. 2007; 13: 814-821
Published online: March 21, 2015
Accepted: February 21, 2015
Received in revised form: February 16, 2015
Received: September 27, 2014
© 2015 European Association for the Study of the Liver. Published by Elsevier Inc. All rights reserved.