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.
Methods
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.
Results
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.
Conclusion
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)Keywords
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Article info
Publication history
Published online: March 21, 2015
Accepted:
February 21,
2015
Received in revised form:
February 16,
2015
Received:
September 27,
2014
Identification
Copyright
© 2015 European Association for the Study of the Liver. Published by Elsevier Inc. All rights reserved.
