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24-02-2024 | Entecavir | Original Article

Synthesis and Biologic Evaluation of an Iodine-Labeled Entecavir Derivative for Anti-hepatitis B Virus Activity

Authors: Mu hua Cheng, Liang jun Xie

Published in: Nuclear Medicine and Molecular Imaging

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Abstract

Purpose

To label entecavir (ETV) with radioiodine and evaluate its effect on inhibiting hepatitis B virus (HBV) secretion and replication in vitro as well as its biodistribution in BALB/c mice.

Methods

125I-ETV was synthesized via binding a vinyl tributyltin group to ETV and producing electrophilic iodination of the group. Its chemical properties were assessed using traditional methods. Upon intravenous injection of 125I-ETV into BALB/c mice, the radioactivity of the critical organs was detected. In vitro, the anti-HBV activity of 125I-ETV was investigated using HepG2.2.15 cell culture model. Confocal microscopy was used to analyze the cell apoptosis. Culture supernatant samples were used for measuring HBV surface antigen (HBsAg) and HBV e antigen (HBeAg) by enzyme-linked immunosorbent assay. Intracellular HBV pregenomic RNA (pgRNA), DNA, and covalently closed circular DNA (cccDNA) were measured by real-time fluorescence quantitative PCR.

Results

The radiochemical purity of 125I-ETV was greater than 95% after incubation in freshly serum within 48 h. The three highest radioactivities were in the stomach, intestine, and liver after intravenous injection at 0.5 h, 2 h, and 24 h. The confocal fluorescence imaging showed that 125I-ETV did not induce cell apoptosis after treatment for 96 h. 125I-ETV decreases HBsAg and HBeAg secretions as well as intracellular HBV pgRNA, DNA, and cccDNA copies in a dose-dependent manner. Moreover, the anti-HBV activity of 125I-ETV is greater than that of ETV.

Conclusions

The study outcome establishes 125I-ETV as a candidate for anti-HBV. However, it is still in need of further endorsement and optimization by animal model studies before using 125I-ETV to treat chronic HBV disease.
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Metadata
Title
Synthesis and Biologic Evaluation of an Iodine-Labeled Entecavir Derivative for Anti-hepatitis B Virus Activity
Authors
Mu hua Cheng
Liang jun Xie
Publication date
24-02-2024
Publisher
Springer Nature Singapore
Published in
Nuclear Medicine and Molecular Imaging
Print ISSN: 1869-3474
Electronic ISSN: 1869-3482
DOI
https://doi.org/10.1007/s13139-024-00849-2