Molecularly Targeted MR Imaging Agent in Liver Fibrosis: High                     Sensitivity and Low Gadolinium Mean High Translational Potential

Pomper, Martin G.; Lee, Seulki

doi:10.1148/radiol.2018180084

Cited by 4 publications

(1 citation statement)

References 11 publications

(7 reference statements)

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“…In the clinic, MRI and ultrasound imaging are two powerful and widely used noninvasive methods for the detection of liver stiffness. However, while they provide good diagnosis for advanced fibrosis, it is still difficult to detect very early fibrosis or small changes. , Molecular targeting probes would be better for detection and therapeutic drug delivery. The 99m Tc-sulfur colloid liver scan is FDA-approved, but it is used for Kupffer cell scans and lacks liver-specific characteristics.…”

Section: Introductionmentioning

confidence: 99%

Use of ¹¹¹In-Hexavalent Lactoside for Liver Reserve Estimation in Rodents with Thioacetamide-Induced Hepatic Fibrosis

Wang

Chien

et al. 2018

Mol. Pharmaceutics

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Many biochemical tests detecting the presence of liver disease are not liver-specific and may be abnormal in nonhepatic conditions. The asialoglycoprotein receptor (ASGPR) is a hepatocyte-specific receptor for Gal/GalNAc-terminated glycopeptide or glycoprotein. The number of these receptors decreases in patients with chronic liver diseases. Here, we aimed to evaluate the use of 111 In-hexavalent lactoside, a known ASGPR imaging biomarker, as a more sensitive probe to detect small changes in liver reserve in animal models of chronic liver injury. Thioacetamide (TAA) treatment via intraperitoneal injection every 2 days in BALB/c mice continued for 1, 2, 3, or 4 months. The liver fibrosis stages were determined by Sirius Red staining and were based on the METAVIR classification method. Serum transaminase enzymes (alanine transaminase (ALT) and aspartate transaminase (AST)), alkaline phosphatase, albumin, and bilirubin were measured using a FUJI FDC3500 i/s analyzer. The ASGPR staining was performed by immunohistocytochemical stain. The percentages of fibrosis and ASGPR were calculated using ImageJ software after collagen staining and anti-ASGPR staining, respectively. A nanoSPECT/CT was used for molecular imaging and liver uptake measurement. We observed fibrosis grades of F0−F1 in mice treated with TAA for 1 month, F2 in mice treated for 2 months, F3−F4 in mice treated for 3 months, and F4 in mice treated for 4 months. The levels of ALT and albumin were not significantly different in the TAA groups from those in the controls. Although the average levels of AST, alkaline phosphatase, and bilirubin in the TAA groups were different from those in the control group, there was little difference between TAA groups. More sensitive distinctions among TAA groups were detected in 111 In-hexavalent lactoside uptake of ASGPR, ASGPR staining, and fibrosis % than when using the conventional AST, ALT, albumin, alkaline phosphatase, and bilirubin tests. The absorption and distribution of 111 In-hexavalent lactoside were lower in the chronic hepatitis models than the normal controls. The liver reserves measured by 111 In-hexavalent lactoside uptake were 71.7 ± 7.5% and 50.9 ± 5.6% after 1 and 2 months, respectively, of TAA treatment. As an ASGPR biomarker, 111 In-hexavalent lactoside has higher sensitivity than traditional liver function tests and collagen stain to provide more objective data for evaluating compensated cirrhosis or changes in liver damage. ASGPR staining can reflect the regenerated hepatocytes, but the need for a biopsy limits its use. 111 Inhexavalent lactoside measurement is comparable with ASGPR staining, which suggests that 111 In-hexavalent lactoside measurement will be more useful as a practical, noninvasive test of chronic liver injury.

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Section: Introductionmentioning

confidence: 99%

Use of ¹¹¹In-Hexavalent Lactoside for Liver Reserve Estimation in Rodents with Thioacetamide-Induced Hepatic Fibrosis

Wang

Chien

et al. 2018

Mol. Pharmaceutics

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Artesunate alleviates liver fibrosis by regulating ferroptosis signaling pathway

Kong

Liu

Cheng

2019

Biomedicine & Pharmacotherapy

230

162

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Non-invasive diagnosis of liver fibrosis: A review of current imaging modalities

Shen

2020

Gastroenterología y Hepatología (English Edition)

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Molecularly Targeted MR Imaging Agent in Liver Fibrosis: High Sensitivity and Low Gadolinium Mean High Translational Potential

Cited by 4 publications

References 11 publications

Use of ¹¹¹In-Hexavalent Lactoside for Liver Reserve Estimation in Rodents with Thioacetamide-Induced Hepatic Fibrosis

Use of ¹¹¹In-Hexavalent Lactoside for Liver Reserve Estimation in Rodents with Thioacetamide-Induced Hepatic Fibrosis

Artesunate alleviates liver fibrosis by regulating ferroptosis signaling pathway

Non-invasive diagnosis of liver fibrosis: A review of current imaging modalities

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Molecularly Targeted MR Imaging Agent in Liver Fibrosis: High Sensitivity and Low Gadolinium Mean High Translational Potential

Cited by 4 publications

References 11 publications

Use of 111In-Hexavalent Lactoside for Liver Reserve Estimation in Rodents with Thioacetamide-Induced Hepatic Fibrosis

Use of 111In-Hexavalent Lactoside for Liver Reserve Estimation in Rodents with Thioacetamide-Induced Hepatic Fibrosis

Artesunate alleviates liver fibrosis by regulating ferroptosis signaling pathway

Non-invasive diagnosis of liver fibrosis: A review of current imaging modalities

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Product

Resources

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Use of ¹¹¹In-Hexavalent Lactoside for Liver Reserve Estimation in Rodents with Thioacetamide-Induced Hepatic Fibrosis

Use of ¹¹¹In-Hexavalent Lactoside for Liver Reserve Estimation in Rodents with Thioacetamide-Induced Hepatic Fibrosis