Receptor measurements via Tc-GSA kinetic modeling are proportional to functiosal hepatocellular mass

MIKI, K; KUBOTA, K; INOUE, Y; VERA, D; MAKUUCHI, M

doi:10.1016/s0016-5085(01)82723-2

Cited by 20 publications

(26 citation statements)

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“…We compared the glycosylation of GGT isolated from human kidney to GGT isolated from human liver. The liver differs from the kidney in that 95% of the total mass of the liver is composed of a single cell type, the hepatocyte (43). GGT is expressed by hepatocytes and is localized to their bile canalicular surface.…”

Section: Discussionmentioning

confidence: 99%

Analysis of Site-specific Glycosylation of Renal and Hepatic γ-Glutamyl Transpeptidase from Normal Human Tissue

West

Segu

Feasley

et al. 2010

Journal of Biological Chemistry

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The cell surface glycoprotein ␥-glutamyl transpeptidase (GGT) was isolated from healthy human kidney and liver to characterize its glycosylation in normal human tissue in vivo. GGT is expressed by a single cell type in the kidney. The spectrum of N-glycans released from kidney GGT constituted a subset of the N-glycans identified from renal membrane glycoproteins. Recent advances in mass spectrometry enabled us to identify the microheterogeneity and relative abundance of glycans on specific glycopeptides and revealed a broader spectrum of glycans than was observed among glycans enzymatically released from isolated GGT. A total of 36 glycan compositions, with 40 unique structures, were identified by site-specific glycan analysis. Up to 15 different glycans were observed at a single site, with site-specific variation in glycan composition. N-Glycans released from liver membrane glycoproteins included many glycans also identified in the kidney. However, analysis of hepatic GGT glycopeptides revealed 11 glycan compositions, with 12 unique structures, none of which were observed on kidney GGT. No variation in glycosylation was observed among multiple kidney and liver donors. Two glycosylation sites on renal GGT were modified exclusively by neutral glycans. In silico modeling of GGT predicts that these two glycans are located in clefts on the surface of the protein facing the cell membrane, and their synthesis may be subject to steric constraints. This is the first analysis at the level of individual glycopeptides of a human glycoprotein produced by two different tissues in vivo and provides novel insights into tissue-specific and site-specific glycosylation in normal human tissues.

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Section: Discussionmentioning

confidence: 99%

Analysis of Site-specific Glycosylation of Renal and Hepatic γ-Glutamyl Transpeptidase from Normal Human Tissue

West

Segu

Feasley

et al. 2010

Journal of Biological Chemistry

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“…The model permits quantitative measurement of total receptor amount (R tot ) and hepatic blood flow, without blood samples. R tot correlates with the number of viable hepatocytes and can be used to assess functional liver mass (40).…”

Section: Kinetics and Quantitative Measurement Of Liver Functionmentioning

confidence: 99%

Nuclear Imaging Techniques for the Assessment of Hepatic Function in Liver Surgery and Transplantation

Graaf¹,

Bennink²,

Veteläinen³

et al. 2010

J Nucl Med

138

120

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This review describes the application of 2 nuclear imaging techniques for assessment of hepatic function in the setting of liver surgery and transplantation. The biochemical and technical background, as well as the clinical applications, of 99m Tc-labeled diethylenetriaminepentaacetic acid galactosyl human serum albumin (GSA) scintigraphy and hepatobiliary scintigraphy (HBS) with 99m Tc-labeled iminodiacetic acid derivates is discussed. 99m Tc-mebrofenin is considered the most suitable iminodiacetic acid agent for 99m Tc-HBS. 99m Tc-GSA scintigraphy and 99m Tcmebrofenin HBS are based on 2 different principles. 99m Tc-GSA scintigraphy is a receptor-mediated technique whereas HBS represents hepatic uptake and excretion function. Both techniques are noninvasive and provide visual and quantitative information on both total and regional liver function. They can be used for preoperative assessment of future remnant liver function, follow-up after preoperative portal vein embolization, and evaluation of postoperative liver regeneration. In liver transplantation, these methods are used to assess graft function and biliary complications.

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“…The functional imaging of liver ASGP-R is of both diagnostic and prognostic value during the treatment of liver pathologies (e.g., cancer and hepatitis B). Several hepatic imaging agents have been described that rely on macromolecular bioconjugates and polymer scaffolds as carriers, bearing efficient reporter groups and pendant b-galactoside and/or N-acetyl-b-galactosaminyl residues as targeting groups of the ASGP-R. A conjugate of a neoglyco protein, galactosylated serum albumin (GSA), with [ Tc]-DTPA-GSA [17], has been used in single photon emission computed tomography (SPECT) hepatic imaging of rodents and humans to study liver pathologies [18][19][20][21]. The hepatocyte-specific nature of the ASGP-R and the fact that it is still expressed (although in reduced numbers) on hepatoma cells makes it possible to detect liver-cancer metastases to other organs, such as bone [22].…”

Section: Ln-chelate Glycoconjugates As Molecular Imaging Casmentioning

confidence: 99%

Glycoconjugate Probes and Targets for Molecular Imaging Using Magnetic Resonance

2010

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Review Molecular recognition of sugar residues applied in molecular imagingMolecular imaging aims at probing the molecular abnormalities that are the basis of diseases rather than to image their effects [1]. An important prerequisite of this approach is the selection of appropriate markers of disease and of targeting vectors to recognize them. The latter can include low-molecular weight substrates for enzymes or high-molecular weight affinity ligands, such as monoclonal antibodies, hormone analogs and recombinant proteins. Of the three major classes of biomolecules (proteins, nucleic acids and carbohydrates), the latter class is the least exploited in molecular imaging. However, a dense layer of glyco conjugates covers all cells and carbohydrate mediated cellular recognition plays an important role in nature, both in normal and malignant processes, such as cell-cell communication, infection, inflammation, metastasis and reproduction. As carriers of information, the carbohydrates have far greater potential than proteins and nucleic acids; three different nucleotides or amino acids can generate only six distinguishable structures, while over 1000 structures can be built up from three different monosaccharides [2]. This level of complexity is probably the reason for the fact that the exploration of these compounds in molecular imaging is lagging behind [3]. Recently, significant progress has been made in glycochemistry and glycobiology; for example, automated solid-phase synthesis of oligo saccharides has become possible [4], carbohydrate-based vaccines have been developed [5] and high-throughput methods have been designed for the screening of molecular interactions [6]. The exciting new developments in glycoscience are opening way for new challenges in exploring the full potential of carbohydrates in molecular imaging. Therefore, here we give an overview of the recent literature on the use of glycoconjugates either as probes or targets in molecular imaging using MRI.MRI contrast agents (CAs) are broadly described as positive or negative, depending on whether they give rise to a brightening or a darkening effect on the MR image, respectively. The positive or brightening effect predominantly relates to the longitudinal proton relaxation time (T 1 ) and the negative or darkening effect predominantly relates to the transverse proton relaxation time (T 2 ). To date, the majority of commercially available and clinically applied positive CAs are Gd 3+ complexes of the polyaminocarboxylates diethylene triamine pentacetic acid (DTPA) and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) (see FiguRe 1 for some typical examples) and negative CAs are various iron oxide particles. These agents are not actively targeting. The targeted CAs for application in molecular imaging that are currently under development and described below are generally based on compounds 1 (Gd-DTPA) and 2 (Gd-DOTA), as well as iron oxide nanoparticles.Glycoconjugate probes and targets for molecular imaging using magnetic resonanceRecently...

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Receptor measurements via Tc-GSA kinetic modeling are proportional to functiosal hepatocellular mass

Cited by 20 publications

References 0 publications

Analysis of Site-specific Glycosylation of Renal and Hepatic γ-Glutamyl Transpeptidase from Normal Human Tissue

Analysis of Site-specific Glycosylation of Renal and Hepatic γ-Glutamyl Transpeptidase from Normal Human Tissue

Nuclear Imaging Techniques for the Assessment of Hepatic Function in Liver Surgery and Transplantation

Glycoconjugate Probes and Targets for Molecular Imaging Using Magnetic Resonance

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